and Human Services (HHS)
EXPIRED
MEDICATIONS DEVELOPMENT TO TREAT ALCOHOLISM (SBIR/STTR)
RELEASE DATE: December 4, 2003
RFA Number: RFA-AA-04-002 (This RFA has been reissued, see RFA-AA-06-006
and RFA-AA-06-007)
Department of Health and Human Services (DHHS)
PARTICIPATING ORGANIZATION:
National Institutes of Health (NIH)
(http://www.nih.gov)
COMPONENT OF PARTICIPATING ORGANIZATION:
National Institute of Alcohol Abuse and Alcoholism (NIAAA)
(http://www.niaaa.nih.gov)
CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER: 93.273
LETTER OF INTENT RECEIPT DATE: March 15, 2004
APPLICATION RECEIPT DATE: April 14, 2004
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Project Period and Amount of Award
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Supplementary Instructions
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
o References
NOTICE: This Request for Application (RFA) must be read in conjunction
with the current OMNIBUS SOLICITATION OF THE NATIONAL INSTITUTES OF
HEALTH, CENTERS FOR DISEASE CONTROL AND PREVENTION, and FOOD AND DRUG
ADMINISTRATION FOR SMALL BUSINESS INNOVATION RESEARCH (SBIR) AND SMALL
BUSINESS TECHNOLOGY TRANSFER (STTR) GRANT APPLICATIONS. The
solicitation (see
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf [PDF] or
http://grants.nih.gov/grants/funding/sbirsttr1/index.doc [MS Word])
contains information about the SBIR and STTR programs, regulations
governing the programs, and instructional information for submission.
All of the instructions within the SBIR/STTR Omnibus Solicitation apply
with the following exceptions:
o Application Receipt Date April 14, 2004
o Initial review convened by the NIAAA Division of Extramural Activities
PURPOSE OF THIS RFA
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is
seeking research grant applications on the development of medications
for alcohol abuse/dependence and alcohol-related diseases.
Investigations are needed on pharmacological agents that prevent or
reduce alcohol intake by decreasing the alcohol craving/urge to drink
and/or alleviating the negative symptoms associated with drinking
cessation(e.g., protracted withdrawal syndrome). Applications are also
encouraged to develop and test agents for the treatment of acute
alcohol withdrawal and alcohol intoxication. Evaluations of
pharmacological agents to treat alcohol-induced diseases, such as
alcoholic liver diseases, are encouraged as well.
RESEARCH OBJECTIVES
Background
During the past decade advances have been made in medications
development to treat alcoholism (see comprehensive reviews by Garbutt
et al., 1999; Swift, 1999; and Kranzler, 2000). The fruits of these
efforts have been highlighted by the FDA approval of naltrexone, the
first medication approved for alcoholism in the 50 years since the
introduction of disulfiram. Advances have also been made in
understanding the biological mechanisms underlying alcohol drinking.
For example, it is now known that multiple neurotransmitter,
neuromodulator, and hormonal systems can alter alcohol intake and are
either directly or indirectly involved in problematic drinking. These
include opioid, serotonin, dopamine, gamma-aminobutyric acid (GABA),
glutamate, neuropeptide Y (NPY), cannabinoid, and hypothalamic-
pituitary-adrenal (HPA) systems (Litten et al., 1996; Roberts and Koob,
1997; Johnson and Ait-Daoud, 2000;). This recent knowledge has led to
many biological targets for testing novel pharmacological agents.
To date, the two most promising and successful medications are
naltrexone and acamprosate. Two important clinical trials of naltrexone
(Volpicelli et al., 1992 and O'Malley et al., 1992) first demonstrated
efficacy of naltrexone in alcohol dependent patients and contributed
significantly to FDA approval of naltrexone. Although naltrexone is not
a "magic bullet" for alcoholism treatment, it appears to have a
moderate effect in reducing drinking, particularly reducing relapse to
heavy drinking (Volpicelli et al., 1997; Anton et al., 1999; Morris et
al., 2001; Heinala et al., 2001). Recent studies have suggested that
patient compliance plays a significant role in the efficacy of
naltrexone (Volpicelli et al., 1997; Chick et al., 2000; Monti et al.,
2001). Nonetheless, naltrexone may not be effective for all alcoholics
(Kranzler et al., 2000; Krystal et al, 2001). Several studies are
currently being funded to address issues surrounding the clinical
use of naltrexone such as how long should patients receive naltrexone;
what is the optimal dose; what types of alcoholics respond best; what
is the optimal combination with behavioral/psychosocial interventions;
and can the efficacy of naltrexone be improved by combining it with
other medications. Finally, nalmefene, another opioid antagonist, has
also demonstrated effectiveness in preventing relapse to heavy drinking
in alcohol- dependent patients (Mason et al., 1999).
Acamprosate has been studied extensively in Europe and is currently
approved for alcoholism treatment in 37 countries. Sixteen controlled
clinical trials have been conducted across 11 European countries
involving more than 4,600 alcohol dependent patients. The studies have
consistently shown that individuals treated with acamprosate are more
likely to complete treatment, have longer times to their first drink,
have greater abstinence rates, and demonstrate longer cumulative
abstinence durations than placebo-treated patients (Mason and Ownby,
2000). Acamprosate's mechanism of action has yet to be definitively
identified, although several studies suggest that it may modulate
activity of the glutamate system (Littleton, 1995; Spanagel and
Zieglgansberger, 1997).
The serotonergic system has also been implicated in drinking behavior.
The serontonin3 (5-HT3) receptor has been shown to regulate release of
dopamine in the mesolimbic area, particularly in the nucleus accumbens.
Ondansetron, a 5-HT3 antagonist, has been demonstrated to reduce desire
to drink in humans and to augment stimulant and sedative effects of
alcohol (Johnson et al., 1993; Swift et al., 1996). A 12-week dosage
trial of ondansetron has recently been completed in early onset
alcoholics and late onset alcoholics (Johnson et al., 2000b).
Ondansetron reduced frequency and quantity of alcohol consumption in
early onset alcoholics, but not in the late onset alcoholics.
Interestingly, a preliminary study combining ondansetron and naltrexone
showed that the combination reduced alcohol craving and enhanced
drinking outcome to a greater extent than had each demonstrated alone
(Johnson et al., 2000a; Ait-Daoud et al., 2001).
Results of selective serotonin reuptake inhibitors (SSRIs) in human
alcohol trials have been inconsistent (Pettinati, 1996, Kranzler,
2000). Recent data, however, suggest that subpopulations of alcohol
dependent patients respond differentially to the SSRIs. For example,
Kranzler et al. (1996) and Pettinati et al. (2000) showed that higher-
risk/severity type B alcoholics had less favorable treatment outcome to
SSRIs than lower-risk/severity type A alcoholics. Cornelius et al.
(1997) found that fluoxetine reduced depressive symptoms and
alcohol intake in severe inpatient populations of alcoholics with major
depression and suicide risk. In contrast, Pettinati et al. (2001) and
McGrath (1998) reported that fluoxetine and sertraline were no better
than placebo in improving depression and reducing drinking in a less
severe population of depressed alcoholics.
Since all medications discussed above produce small to medium
effects in reducing or preventing drinking, development and evaluation
of new and more potent medications remains a high priority. Several
promising pharmacological agents could lead to clinical testing. These
include, but are not limited to, memantine, a non-competitive NMDA
antagonist (Holter et al., 1996); kudzu and its purified active
components (e.g., puerarin) (Keung and Vallee, 1993; Lin et al., 1996);
corticotropin-releasing factor (CRF) antagonists (Bell et al., 1998; Le
et al., 2000; Richter et al., 2000); opioid subtype receptor
antagonists such as delta2 antagonist naltriben (June et al., 1999); 6-
beta naltrexol, an active metabolite of naltrexone (Rukstalis et al.,
2000); synthetic neurosteroids (Morrow et al., 1999); 1-
aminocyclopropanecarboxylic acid (ACPC), a NMDA partial agonist
(Stromberg et al., 1999); FG 5974 (and its analogues), a 5-HT1A
agonist/5-HT2A antagonist (Roberts et al., 1998), and agents with
selective affinity to GABAA alpha1 or GABAA alpha5 receptor subunits
(June et al., 2001, Harvey et al., 2002).
A spectrum of neurotransmitter systems (e.g., GABA, NMDA, 5-HT,
dopamine), neuropeptide systems (neuropeptide Y, leptin), signal
transduction pathways (PKA, PKC), and gene transcription factors (delta
fosB) have been implicated in alcohol dependence and craving. New
therapeutic compounds may emerge from further research on known ethanol
targets, or may occur by identifying possible therapeutic targets and
prototype drug candidates through research on systems and mechanisms
not yet examined in relation to alcohol. As basic research reveals
promising targets relevant to alcohol abuse and its consequences,
analogs acquired from existing libraries, or newly-synthesized analogs
developed through computational and combinatorial chemistry can be
screened in vitro or in standardized behavioral assays for potential
therapeutic efficacy.
Advances in molecular genetics (e.g., microarray analysis, targeted
mutations, and proteomics) offer a powerful approach for broad-spectrum
scanning of participants in the adaptive process. Individual gene
clusters or functionally-related proteins can be identified in specific
brain regions in temporal relation to alcohol exposure. Such studies
may identify biochemical pathways and brain circuits which are
preferentially recruited as alcohol dependence develops. Receptors or
pathways involved in alcohol drinking and other alcohol effects can be
disabled selectively with targeted knockout strategies. An unanswered
question facing medical treatment concerns potential targets for
modifying neurological changes underlying craving and alcohol-seeking
after periods of prolonged abstinence.
For pharmacological management of acute alcohol withdrawal,
benzodiazepines have been the most widely used medication over the past
two decades. They have consistently been demonstrated to assuage many
symptoms of withdrawal (Mayo-Smith, 1997). Recent studies have focused
on benzodiazepine dosing strategies. For example, a "loading dose"
technique in which benzodiazepines are given every 1 or 2 hours until
withdrawal symptoms subside, appears effective in preventing over- and
under-dosing of medication (Wartenberg et al., 1990; Sullivan et al.,
1991; Saitz et al., 1994). Yet in spite of their benefits,
benzodiazepines have adverse effects including memory impairment,
drowsiness, lethargy, and cognitive problems.
Finally, progress has been made in elucidating the mechanisms of
alcohol-induced organ damage. In particular, several primary factors
underlying the pathogensis of alcoholic liver disease have been
identified including cytokines and reactive oxygen species (ROS)
(Tsukamoto and Lu, 2001). For example, the administration of antibodies
against the proinflammatory tumor necrosis factor (TNF ?) attenuated
alcohol-induced liver injury in rats (Iimuro et al., 1997). A later
study showed an absence of alcohol liver injury in knockout mice
missing the TNF receptor 1 (Yin et al., 1999). ROS are generated by the
metabolism of alcohol and can also cause damage to the liver (Tsukamoto
and Lu, 2001). ROS are quickly inactivated by antioxidants, such as
glutathione and vitamins A and E. Antioxidants, such as S-adenosyl-L-
methionine (SAMe), have also been shown to reduce alcohol-induced liver
injury in animals. Potential new treatments of alcoholic liver disease
include antioxidants, such as SAMe and vitamin E; as well as other
types of agents including phosphatidylcholine, a phospholipid;
pirfenidone, a new broad- spectrum anti-fibrotic agent; and metformin,
an insulin-sensitizing agent (Lieber, 2001; Miric et al., 2001;
Tsukamoto and Lu, 2001).
SPECIFIC AREAS OF INTEREST BUT NOT LIMITED TO
NIAAA is committed to the development and assessment of pharmacological
agents to treat alcohol use disorders as well as the more prevalent and
severe medical conditions associated with chronic drinking.
Pharmacological agents of interest can be categorized by function as
follows:
- Agents to decrease craving or urge to drink.
- Agents to diminish drinking by alleviating co-occurring psychiatric
pathology and other drug use.
- Agents to treat alcohol-associated liver disease and other end-organ
diseases, such as pancreatitis, cardiomyopathy, and bone disease.
- Agents to treat acute alcohol withdrawal.
- Agents to induce sobriety in intoxicated individuals
Many important clinical priorities and issues exist for these classes
of pharmacological agents and are identified, but not limited, to the
following:
- New and existing pharmacological agents and combinations of those
agents, need to be identified and evaluated in conjunction with
behavioral therapies for alcoholism treatment. Optimal dosing regimens
and length of treatment need to be established. Although NIAAA has
supported projects on the efficacy of the opioid antagonist naltrexone,
the therapeutic potential of other pharmacological agents in the opioid
class is a current research priority. In addition to opioid
antagonists, the therapeutic potential of other types of agents needs
to be assessed. Among these are agents that interact with the
serotonergic, dopaminergic, glutamatergic, GABAergic, NPY, cannabinoid,
and HPA systems as well as herbal preparations.
- Development of pharmacological agents to attenuate negative symptoms
of chronic drinking, sometimes referred to as the "protracted
withdrawal" syndrome. Research on potential pharmacological treatment
of this phenomenon has been quite limited, due to failure to specify
cardinal symptoms associated with sustained sobriety by alcoholics.
Research is needed to establish operational definitions of this event
as is research on agents to reduce the severity of protracted symptoms.
-Factors influencing clinical efficacy of medications to treat alcohol
abuse and dependence can be identified using human laboratory
behavioral pharmacology paradigms. Prior to beginning phase 2 clinical
trials, potential medications can be screened in the laboratory to
determine the following: 1) the medication's impact to reduce craving
for alcohol and/or to diminish the negative symptoms of drinking; 2)
likelihood of adverse events, especially in the presence of alcohol; 3)
pharmacokinetics for medication combinations; and 4) optimal dosing
regimens. Studies are sought which develop and expand use of these
human laboratory paradigms.
- Development of medications to treat alcoholic liver diseases and
other alcohol-related, end-organ diseases. These may include agents
that inactivate excess ROS or alter the production or clearance of
cytokines. In reducing the high mortality from alcoholic hepatitis and
cirrhosis, potential medications that prevent necrosis/inflammation and
avert or reverse the progression of fibrosis are of high priority.
Other potential agents include those that are effective in treating
alcohol-induced portal hypertension, pancreatitis, and bone disease.
- Use of proteomic approaches to identify molecular targets for
medications development for alcohol abuse susceptibility, alcohol
dependence, alcohol consumption, withdrawal, and relapse, and alcohol-
associated medical conditions.
- Synthesis of new compounds based on the molecular structure of
receptors, ion channels, and sites of cellular signal transduction
mechanisms involved in alcohol's actions on the nervous system.
- Screening of existing "off the shelf" compounds for properties
associated with therapeutic efficacy for treating alcohol abuse and
alcohol related conditions.
- Development of alternative medications to treat acute alcohol
withdrawal. Also, assuming the "kindling" effect (the severity of
withdrawal symptoms increases after repeated withdrawal episodes) has
clinical relevance (Becker, 1998), can kindling be effectively curbed
by medications to treat withdrawal?
MECHANISMS OF SUPPORT
This RFA uses the SBIR and STTR mechanisms, which are set-aside
programs. As an applicant, you will be solely responsible for planning,
directing, and executing the proposed project. Future unsolicited,
competing- continuation applications based on this project will compete
with all SBIR/STTR applications and will be reviewed according to the
customary peer review procedures. The anticipated award date is
September 27, 2004. Applications that are not funded in the competition
described in this RFA may be resubmitted as NEW SBIR/STTR applications
using the standard receipt dates for NEW applications described in the
current SBIR/STTR Omnibus Solicitation.
This RFA uses just-in-time concepts. It also uses the modular budgeting
as well as the non-modular budgeting formats. Specifically, if you are
submitting an application budget of $100,000 total costs (direct, F&A
and fee) or less, use the modular budget format. For applications
requesting more than $100,000, use the non-modular budget format.
Instructions for both are described in the current SBIR/STTR Omnibus
Solicitation. This program does not require cost sharing as defined in
the current NIH Grants Policy Statement at
http://grants.nih.gov/grants/policy/nihgps_2001/part_i_1.htm.
Except as otherwise stated in this RFA, awards will be administered
under NIH grants policy as stated in the NIH Grants Policy Statement,
March 2001, available at
http://grants.nih.gov/grants/policy/nihgps_2001.
Applications may be submitted for support as Phase I STTR (R41) or
Phase I SBIR (R43) grants; Phase II STTR (R42) or Phase II SBIR (R44)
grants; or the SBIR/STTR FAST-TRACK option as described in the
SBIR/STTR Omnibus Solicitation. Phase II applications in response to
this RFA will only be accepted as competing continuations of previously
funded NIH Phase I SBIR/STTR awards. The Phase II application must be
a logical extension of the Phase I research but not necessarily a Phase
I project supported in response to this RFA. Fast Track applications
will benefit from expedited evaluation of progress following the Phase
I feasibility study for transition to Phase II funding for expanded
developmental work.
PROJECT PERIOD AND AMOUNT OF AWARD
The SBIR/STTR Omnibus Solicitation indicates the statutory guidelines
of funding support and project duration periods for SBIR and STTR Phase
I and Phase II awards. However, these award levels for time and amount
are statutory guidelines, not ceilings. Therefore, applicants are
encouraged to propose a reasonable budget and project period that is
appropriate for completion of the research project. Deviations from
the guidelines are acceptable, but must be well justified. Applicants
are encouraged to discuss budgetary deviations with NIH program staff
prior to submission of the application. For this RFA, time periods of
up to 2 years for Phase I may be requested. Time periods of up to 3
years may be requested for Phase II. Total costs include direct costs,
F&A, and fee/profit.
FUNDS AVAILABLE
NIAAA intends to commit approximately $2,000,000 to fund 5-10 Phase I
and/or Phase II applications under the SBIR/STTR set-aside funding
mechanism. Although the financial plans of the NIAAA provide support
for this program, awards pursuant to this RFA are contingent upon the
availability of funds and the receipt of a sufficient number of
meritorious applications. At this time, it is not known if competing
renewal applications will be accepted and/or if this RFA will be
reissued.
ELIGIBLE INSTITUTIONS:
Eligibility requirements are described in the SBIR/STTR Omnibus
Solicitation. Only small business concerns are eligible to submit
SBIR/STTR applications. A small business concern is one that, on the
date of award for both Phase I and Phase II agreements, meets ALL of
the criteria as described in the current SBIR/STTR Omnibus
Solicitation.
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to
carry out the proposed research is invited to work with their
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH programs. On an
SBIR application, the principal investigator must have his/her primary
employment (more than 50%) with the small business at the time of award
and for the duration of the project. The PI on an STTR application may
be employed with the small business concern or the participating non-
profit research institution as long as s/he has a formal appointment
with or commitment to the applicant small business concern, which is
characterized by an official relationship between the small business
concern and that individual.
SPECIAL REQUIREMENTS
All applications that list direct costs greater than $500,000 in any
year of the proposed research must have a data sharing plan.
Information on NIH data sharing policy and procedures can be found at:
http://grants.nih.gov/grants/policy/data_sharing/index.htm
WHERE TO SEND INQUIRIES
We encourage your inquiries concerning this RFA and welcome the
opportunity to answer questions from potential applicants. Inquires may
fall into three areas: scientific/research, peer review, and finance or
grants management issues.
o Direct your questions about scientific/research issues to:
NIAAA Program Contacts:
Joanne B. Fertig, Ph.D.
Division of Treatment and Recovery Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 505
Bethesda, MD 20892-7003
[For express mail use, Rockville, MD 20852]
Tel: (301) 443-0635
Fax: (301) 443-8774
Email: [email protected]
Peter B. Silverman, Ph.D., J.D.
Division of Neuroscience and Behavior
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402
Bethesda, MD 20892-7003
[for express mail, use Rockville, MD 20852]
Tel. 301-402-6966
FAX 301-594-0673
Email: [email protected]
o Direct your questions about peer review issues to:
Eugene G. Hayunga, Ph.D.
Chief, Extramural Project Review Branch
Office of Scientific Affairs
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Room 409, MSC 7003
Bethesda, MD 20892-7003
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 443-4375
FAX: (301) 443-6077
o Direct your questions about financial or grants management matters
to:
Judy Fox (formerly Simons)
Chief, Grants Management Branch
Office of Planning and Resource Management
National Institute on Alcohol Abuse and Alcoholism
Willco Building, Suite 504
6000 Executive Boulevard, MSC 7003
Bethesda, MD 20892-7003
[for express mail, use Rockville, MD 20852]
Tel. (301) 443-4704
Fax (301) 443-3891
email: [email protected]
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
Although a letter of intent is not required, is not binding, and does
not affect the review of a subsequent application, the information that
it contains allows NIAAA staff to estimate the potential review
workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning
of this document. The letter of intent should be sent to:
Extramural Project Review Branch
Office of Scientific Affairs
ATTN: RFA-AA-04-002
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Room 409, MSC 7003
Bethesda, MD 20892-7003
Rockville, MD 20852 (for express/courier service)
Telephone: (301) 443-4375
FAX: (301) 443-6077
SUBMITTING AN APPLICATION
The PHS 398 research grant application must be used for all SBIR/STTR
Phase I, Phase II and Fast-Track applications (new and revised.)
Effective October 1, 2003, applications must have a DUN and Bradstreet
(D&B) Data Universal Numbering System (DUNS) number as the Universal
Identifier when applying for Federal grants or cooperative agreements.
The DUNS number can be obtained by calling (866) 705-5711 or through
the web site at http://www.dunandbradstreet.com/. The DUNS number
should be entered on line 11 of the face page of the PHS 398 form. The
PHS 398 is available at
http://grants.nih.gov/grants/funding/phs398/phs398.html. Prepare your
application in accordance with the SBIR/STTR Omnibus Solicitation and
the PHS 398. The NIH will return applications that are not submitted on
the 5/2001 version of the PHS 398. For further assistance contact
GrantsInfo, Telephone: (301) 710-0267, Email: [email protected].
USING THE RFA LABEL: The RFA label available in the PHS 398
application form must be affixed to the bottom of the face page of the
application. Type the RFA number on the label. Failure to use this
label could result in delayed processing of the application such that
it may not reach the review committee in time for review. In addition,
the RFA title and number must be typed on line 2 of the face page of
the application form and the YES box must be marked. The RFA label is
also available at:
http://grants.nih.gov/grants/funding/phs398/labels.doc or
http://grants.nih.gov/grants/funding/phs398/labels.pdf.
SENDING AN APPLICATION TO THE NIH:
Submit a signed, typewritten original of the application, including the
Checklist, and three signed, photocopies, in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (for USPS EXPRESS OR REGULAR MAIL)
Bethesda, MD 20817 (for EXPRESS/COURIER NON-USPS SERVICE)
At the time of submission, two additional copies of the application
must be sent to:
Extramural Project Review Branch
Office of Scientific Affairs
Attn: RFA-AA-04-002
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Blvd., Suite 409
Bethesda, 20892-7003
[for express mail use Rockville, 20852]
Telephone: (301) 443-4375
Fax: (301) 443-6077
RECEIPT OF APPLICATIONS. Applications must be received on or before the
receipt date listed on the first page of this announcement. If an
application is received after that date, it will be returned to the
applicant without review.
Although there is no immediate acknowledgement of the receipt of an
application, applicants are generally notified of the review and
funding assignment within 8 weeks.
The Center for Scientific Research (CSR) will not accept any
application in response to this RFA that is essentially the same as one
currently pending initial review unless the applicant withdraws the
pending application. The CSR will not accept any application that is
essentially the same as one already reviewed. However, when a
previously unfunded application, originally submitted as an
investigator-initiated application, is to be submitted in response to
an RFA it is to be prepared as a NEW application. That is, the
application for the RFA must not include an Introduction describing the
changes and improvements made, and the text must not be marked to
indicate the changes from the previous unfunded version of the
application.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by the NIAAA. Incomplete applications will not be
reviewed.
If the application is not responsive to the RFA, NIH staff may contact
the applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next appropriate NIH review cycle.
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NIAAA in accordance with the review
criteria stated below. As part of the initial merit review, all
applications will:
o Undergo a process in which only those applications deemed to have the
highest scientific merit, generally the top half of the applications
under review, will be discussed and assigned a priority score
o Receive a written critique
o Receive a second level review by the NIAAA National Advisory Council
or Board.
REVIEW CRITERIA
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In the written comments, reviewers will be asked to evaluate the
application in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals within the
context of the SBIR/STTR Program. The scientific review group will
address and consider each of the following criteria in assigning the
application’s overall score:
o Significance
o Approach
o Innovation
o Investigator
o Environment
ALL SBIR/STTR APPLICATIONS
1. Significance: Does the proposed project have commercial potential
to lead to a marketable product or process? Does this study address an
important problem? What may be the anticipated commercial and societal
benefits of the proposed activity? If the aims of the application are
achieved, how will scientific knowledge be advanced? Does the proposal
lead to enabling technologies (e.g., instrumentation, software) for
further discoveries? Will the technology have a competitive advantage
over existing/alternate technologies that can meet the market needs?
2. Approach: Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to the
aims of the project? Is the proposed plan a sound approach for
establishing technical and commercial feasibility? Does the applicant
acknowledge potential problem areas and consider alternative
strategies? Are the milestones and evaluation procedures appropriate?
3. Innovation: Does the project challenge existing paradigms or employ
novel technologies, approaches or methodologies? Are the aims original
and innovative?
4. Investigators: Is the Principal Investigator capable of coordinating
and managing the proposed SBIR/STTR? Is the work proposed appropriate
to the experience level of the Principal Investigator and other
researchers, including consultants and subcontractors (if any)? Are the
relationships of the key personnel to the small business and to other
institutions appropriate for the work proposed?
5. Environment: Is there sufficient access to resources (e.g.,
equipment, facilities)? Does the scientific and technological
environment in which the work will be done contribute to the
probability of success? Do the proposed experiments take advantage of
unique features of the scientific environment or employ useful
collaborative arrangements?
PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of
human subjects and protections from research risk relating to their
participation in the proposed research will be assessed. (See
additional information and criteria included in the section on Federal
Citations, below).
INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy
of plans to include subjects from both genders, all racial and ethnic
groups (and subgroups), and children as appropriate for the scientific
goals of the research. Plans for the recruitment and retention of
subjects will also be evaluated. (See additional information and
Inclusion Criteria in the sections on Federal Citations, below).
Human Subjects:
Protection of Human Subjects from Research Risks - for all studies
involving human subjects. See instructions and "Guidance for Preparing
the Human Subjects Research Section. If an exemption is claimed, is it
appropriate for the work proposed? If no exemption is claimed, are the
applicant's responses to the six required points appropriate? Are human
subjects placed at risk by the proposed study? If so, are the risks
reasonable in relation to the anticipated benefits to the subjects and
others? Are the risks reasonable in relation to the importance of the
knowledge that reasonably may be expected to be gained? Are the plans
proposed for the protection of human subjects adequate?
Inclusion of Women Plan - for clinical research only. Does the
applicant propose a plan for the inclusion of both genders that will
provide their appropriate representation? Does the applicant provide
appropriate justification when representation is limited or absent?
Does the applicant propose appropriate and acceptable plans for
recruitment/outreach and retention of study participants?
Inclusion of Minorities Plan - for clinical research only. Does the
applicant propose a plan for the inclusion of minorities that will
provide their appropriate representation? Does the applicant provide
appropriate justification when representation is limited or absent?
Does the applicant propose appropriate and acceptable plans for
recruitment/outreach and retention of study participants?
Inclusion of Children Plan- for all studies involving human subjects.
Does the applicant describe an acceptable plan in which the
representation of children of all ages (under the age of 21) is
scientifically appropriate and recruitment/retention is addressed
realistically? If not, does the applicant provide an appropriate
justification for their exclusion?
Data and Safety Monitoring Plan for clinical trials only. Does the
applicant describe a Data and Safety Monitoring Plan that defines the
general structure of the monitoring entity and mechanisms for reporting
Adverse Events to the NIH and the IRB?
CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals
are to be used in the project, the required five items described under
Vertebrate Animals (section f of the Research Plan instructions) will
be assessed. If vertebrate animals are involved, are adequate plans
proposed for their care and use? Are the applicant's responses to the
five required points appropriate? Will the procedures be limited to
those that are unavoidable in the conduct of scientifically sound
research?
BIOHAZARDS: Is the use of materials or procedures that are potentially
hazardous to research personnel and/or the environment proposed? Is the
proposed protection adequate?
ADDITIONAL REVIEW CONSIDERATIONS: The following items may be also be
considered by reviewers but will not be included in the determination
of scientific merit.
SHARING RESEARCH DATA: Applicants requesting more than $500,000 in
direct costs in any year of the proposed research must include a data
sharing plan in their application. The reasonableness of the data
sharing plan or the rationale for not sharing research data will be
assessed by the reviewers. However, reviewers will not factor the
proposed data sharing plan into the determination of scientific merit
or priority score. Information on NIH data sharing policy and
procedures can be found at:
http://grants.nih.gov/grants/policy/data_sharing/index.htm
BUDGET: The reasonableness of the proposed budget may be considered.
For all applications, is the percent effort listed for the PI
appropriate for the work proposed? On applications requesting up to
$100,000 total costs, is the overall budget realistic and justified in
terms of the aims and methods proposed? On applications requesting over
$100,000 in total costs, is each budget category realistic and
justified in terms of the aims and methods?
PERIOD OF SUPPORT: The appropriateness of the requested period of
support in relation to the proposed research.
PHASE II APPLICATIONS: In addition to the above review criteria:
- How well did the applicant demonstrate progress toward meeting the
Phase I objectives, demonstrating feasibility, and providing a solid
foundation for the proposed Phase II activity?
- Did the applicant submit a concise Commercialization Plan [formerly
Product Development Plan] that adequately addresses the seven areas
described in the Research Plan item J?
- Does the project carry a high degree of commercial potential, as
described in the Commercialization Plan?
AMENDED APPLICATIONS
In addition to the above criteria, the following criteria will be
applied to revised applications.
- Are the responses to comments from the previous SRG review adequate?
- Are the improvements in the revised application appropriate?
TYPE 2 PHASE II COMPETING CONTINUATION APPLICATIONS
In addition to the above review criteria, the following items will be
applied to ALL Type 2 Competing Continuation Phase II applications in
the determination of scientific merit and the priority score:
o Does the activity as proposed address issues related to Federal
regulatory approval processes?
o What will be the effect of these studies on the concepts or methods
that drive this field?
PHASE I/PHASE II FAST-TRACK APPLICATION REVIEW CRITERIA
For Phase I/Phase II Fast Track applications, the following criteria
also will be applied:
- Does the Phase I application specify clear, appropriate, measurable
goals (milestones) that should be achieved prior to initiating Phase II?
- Did the applicant submit a concise Commercialization Plan [formerly
Product Development Plan] that adequately addresses the seven areas
described in the Research Plan, item J?
- To what extent was the applicant able to obtain letters of interest,
additional funding commitments, and/or resources from the private
sector or non-SBIR/ STTR funding sources that would enhance the
likelihood for commercialization?
- Does the project carry a high degree of commercial potential, as
described in the Commercialization Plan?
Phase I and Phase II Fast-Track applications that satisfy all of the
review criteria will receive a single rating. Failure to provide clear,
measurable goals may be sufficient reason for the scientific review
group to exclude the Phase II application from Fast-Track review.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: March 15, 2004
Application Receipt Date: April 14, 2004
Peer Review Date: June/July 2004
Council Review: September 2004
Earliest Anticipated Start Date: September 27, 2004
AWARD CRITERIA
Applications submitted in response to an RFA will compete for available
funds with all other recommended SBIR and STTR applications. The
following will be considered in making funding decisions:
o Scientific merit of the proposed project as determined by peer review
o Availability of funds
o Relevance to program priorities
For FAST-TRACK applications, the Phase II portion may not be funded
until a Phase I final report and other documents necessary for
continuation have been received and assessed by program staff that the
Phase I milestones have been successfully achieved.
REQUIRED FEDERAL CITATIONS
HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that
applications and proposals involving human subjects must be evaluated
with reference to the risks to the subjects, the adequacy of protection
against these risks, the potential benefits of the research to the
subjects and others, and the importance of the knowledge gained or to
be gained.
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm
DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required
for all types of clinical trials, including physiologic, toxicity, and
dose-finding studies (phase I); efficacy studies (phase II); efficacy,
effectiveness and comparative trials (phase III). The establishment of
data and safety monitoring boards (DSMBs) is required for multi-site
clinical trials involving interventions that entail potential risk to
the participants. (NIH Policy for Data and Safety Monitoring, NIH
Guide for Grants and Contracts, June 12, 1998:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
SHARING RESEARCH DATA: Starting with the October 1, 2003 receipt date,
investigators submitting an NIH application seeking $500,000 or more in
direct costs in any single year are expected to include a plan for data
sharing or state why this is not possible.
http://grants.nih.gov/grants/policy/data_sharing. Investigators should
seek guidance from their institutions, on issues related to
institutional policies, local IRB rules, as well as local, state and
Federal laws and regulations, including the Privacy Rule. Reviewers
will consider the data sharing plan but will not factor the plan into
the determination of the scientific merit or the priority score.
INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the
policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research
projects unless a clear and compelling justification is provided
indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43).
All investigators proposing clinical research should read the "NIH
Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research - Amended, October, 2001," published in the NIH Guide
for Grants and Contracts on October 9, 2001
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines are available at
http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm
The amended policy incorporates: the use of an NIH definition of
clinical research; updated racial and ethnic categories in compliance
with the new OMB standards; clarification of language governing NIH-
defined Phase III clinical trials consistent with the new PHS Form 398;
and updated roles and responsibilities of NIH staff and the extramural
community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or
protocols must provide a description of plans to conduct analyses, as
appropriate, to address differences by sex/gender and/or racial/ethnic
groups, including subgroups if applicable; and b) investigators must
report annual accrual and progress in conducting analyses, as
appropriate, by sex/gender and/or racial/ethnic group differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS:
The NIH maintains a policy that children (i.e., individuals under the
age of 21) must be included in all human subjects research, conducted
or supported by the NIH, unless there are scientific and ethical
reasons not to include them. This policy applies to all initial (Type
1) applications submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines" on the inclusion of children as
participants in research involving human subjects that is available at
http://grants.nih.gov/grants/funding/children/children.htm
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH
policy requires education on the protection of human subject
participants for all investigators submitting NIH proposals for
research involving human subjects. You will find this policy
announcement in the NIH Guide for Grants and Contracts Announcement,
dated June 5, 2000, at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of
research on hESCs can be found at http://stemcells.nih.gov/index.asp
and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the
NIH Human Embryonic Stem Cell Registry will be eligible for Federal
funding (see http://escr.nih.gov). It is the responsibility of the
applicant to provide, in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC
line(s) to be used in the proposed research. Applications that do not
provide this information will be returned without review.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:
The Office of Management and Budget (OMB) Circular A-110 has been
revised to provide public access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are (1)
first produced in a project that is supported in whole or in part with
Federal funds and (2) cited publicly and officially by a Federal agency
in support of an action that has the force and effect of law (i.e., a
regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has
provided guidance at
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application
should include a description of the archiving plan in the study design
and include information about this in the budget justification section
of the application. In addition, applicants should think about how to
structure informed consent statements and other human subjects
procedures given the potential for wider use of data collected under
this award.
STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION:
The Department of Health and Human Services (DHHS) issued final
modification to the Standards for Privacy of Individually Identifiable
Health Information , the Privacy Rule, on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the
protection of individually identifiable health information, and is
administered and enforced by the DHHS Office for Civil Rights (OCR).
Those who must comply with the Privacy Rule (classified under the Rule
as covered entities ) must do so by April 14, 2003 (with the exception
of small health plans which have an extra year to comply).
Decisions about applicability and implementation of the Privacy Rule
reside with the researcher and his/her institution. The OCR website
(http://www.hhs.gov/ocr/) provides information on the Privacy Rule,
including a complete Regulation Text and a set of decision tools on Am
I a covered entity? Information on the impact of the HIPAA Privacy
Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts
can be found at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and
proposals for NIH funding must be self-contained within specified page
limitations. Unless otherwise specified in an NIH solicitation,
Internet addresses (URLs) should not be used to provide information
necessary to the review because reviewers are under no obligation to
view the Internet sites. Furthermore, we caution reviewers that their
anonymity may be compromised when they directly access an Internet
site.
HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting priority
areas. This RFA is related to one or more of the priority areas.
Potential applicants may obtain a copy of "Healthy People 2010" at
http://www.health.gov/healthypeople.
AUTHORITY AND REGULATIONS: This program is described in the Catalog of
Federal Domestic Assistance at http://www.cfda.gov/ and is not subject
to the intergovernmental review requirements of Executive Order 12372
or Health Systems Agency review. Awards are made under the
authorization of Sections 301 and 405 of the Public Health Service Act
as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52
and 45 CFR Parts 74 and 92. All awards are subject to the terms and
conditions, cost principles, and other considerations described in the
NIH Grants Policy Statement. The NIH Grants Policy Statement can be
found at http://grants.nih.gov/grants/policy/policy.htm
The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products. In
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a
facility) in which regular or routine education, library, day care,
health care, or early childhood development services are provided to
children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.
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NIH Funding Opportunities and Notices
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Department of Health and Human Services (HHS) |
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NIH... Turning Discovery Into Health® |
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