Full Text DK-97-003
 
HELICOBACTER PYLORI AND ITS RELATIONSHIP TO DIGESTIVE DISEASES AND
CANCER
 
NIH GUIDE, Volume 26, Number 2, January 17, 1997
 
RFA:  DK-97-003
 
P.T. 34

Keywords: 
  Cancer/Carcinogenesis 
  Digestive Diseases & Disorders 
  Infectious Diseases/Agents 
  Epidemiology 

 
National Institute of Diabetes and Digestive and Kidney Diseases
National Cancer Institute
National Institute of Allergy and Infectious Diseases
Office of Research on Minority Health
American Digestive Health Foundation
 
Letter of Intent Receipt Date:  March 21, 1997
Application Receipt Date:  April 22, 1997
 
PURPOSE
 
The National Institute of Diabetes and Digestive and Kidney Diseases,
the National Cancer Institute, the National Institute of Allergy and
Infectious Diseases (NIAID), and the Office of Research on Minority
Health in partnership with the American Digestive Health Foundation
invite applications for basic and clinical research focusing on the
role of Helicobacter pylori infection in peptic ulcer disease,
nonulcer dyspepsia, and gastric cancer, particularly in minority
populations.  Studies on the epidemiology of Helicobacter pylori in
minority populations, genetic susceptibility to and the acquisition
of Helicobacter infection, the role of Helicobacter in development
and the regulation of the inflammatory response are encouraged.
 
Investigations on the virulence factors of the bacterium, molecular
events involved in the etiology of gastric cancer in relationship to
Helicobacter pylori and the impact of eradication of the organism
should provide important strategies for improving the quality of
patient care.
 
In recognition of the importance of these research questions, the
American Digestive Health Foundation, a cooperative effort of the
American Gastroenterological Association, the American Society of
Gastrointestinal Endoscopy, and the American Association for the
Study of Liver Diseases, will be providing partial funding through
the NIH for the direct costs of the portfolio of grants that receive
support under this initiative.
 
HEALTHY PEOPLE 2000
 
The PHS is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This RFA, Helicobacter Pylori
and its Relationship to Digestive Diseases and Cancer, is related to
the area of chronic disabling conditions.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0 or Summary Report:  Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing Office,
Washington, DC 20402-9325 (telephone 202-512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit and
nonprofit organizations, public or private, such as universities,
colleges, and eligible agencies of the Federal Government.  Foreign
institutions are not eligible for First Independent Research Support
and Transition (FIRST) (R29) awards.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators.
 
MECHANISM OF SUPPORT
 
The support for this RFA will be through the NIH research project
grant (R01) award, the FIRST (R29) award, and the small grants (R03)
award.  The research project grant award (R01) is the investigator
initiated grant-in-aid.  FIRST (R29) award applicants must adhere to
the R29 Administrative Guidelines (rev. Feb. 94) for eligibility,
budget and period of award.  Potential R29 applicants should refer to
the announcement on "Just-in-Time Procedures for FIRST and Career
Awards" (NIH Guide for Grants and Contracts, Vol. 25, No. 10, March
29, 1996).  The small grants research program (R03) provides limited
funds (maximum of $50,000 direct costs per year) for short term (up
to two years) research projects.  These grants are non-renewable, but
continuation of projects developed under this program can be
supported by the investigator-initiated research project grant (R01)
mechanism.  Applicants will be responsible for the planning,
direction, and execution of the propose project.
 
This RFA is a one-time solicitation.  Generally, future unsolicited
competing continuation applications will compete with all
investigator-initiated applications.  The total requested project
period for applications submitted in response to this RFA may not
exceed five years.  The earliest possible award date will be July 1,
1997.
 
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC program director or a Principal Investigator must be included
with the application.
 
FUNDS AVAILABLE
 
For FY 97, $2.5 million in total costs will be committed to fund
applications submitted in response to this RFA.  It is anticipated
that 10 to 12 awards will be made.  However, this funding level is
dependent upon the receipt of a sufficient number of applications of
high scientific merit.  In order to help meet NIH goals for managing
the costs of biomedical research, applicants must limit their
requests to not more than $160,000 direct costs for the initial
budget period.  Although this program is provided for in the
financial plans of the NIDDK, ORMH, NCI, and the American Digestive
Health Foundation (ADHF), the award of grants pursuant to this RFA is
also contingent upon the availability of funds for this purpose.
 
RESEARCH OBJECTIVES
 
Background
 
Following the 1994 NIH Consensus Conference on Helicobacter Pylori in
Peptic Ulcer, the controversy of the role of Helicobacter in
gastrointestinal disease was settled.  The evidence presented at the
conference and subsequent research have clearly established
Helicobacter as a cause of chronic gastritis and peptic ulcer
disease, and a strong cofactor in the development of gastric cancer.
 
The prevalence of H. pylori in the United States has been shown to
increase with age, from 10 to 15 percent in people 15-20 years old to
50 to 67 percent in people 60 years of age or greater (5,6).  Also,
there is a higher prevalence of H. pylori infection in minorities
(African Americans and Hispanics) in all age groups. Rates of H.
pylori infection in African Americans are on average approximately
one third higher than those of Caucasians (7,8).  The rate of
increase of H. pylori acquisition in adult African Americans is the
same as adult whites, indicating that the higher prevalence of H.
pylori infection in African Americans is likely secondary to
increased childhood exposure to this bacterium.  Infection is equally
common among men and women.
 
Despite the many investigations, there are still gaps in our
knowledge about the bacterium.  Data strongly support H. pylori as an
etiologic factor in the development of peptic ulcers.  Antibiotic
treatment of H. pylori- associated gastritis in patients with peptic
ulcer disease shows that eradication of the organism (with
antibiotics) is as effective in healing ulcers as H2 receptor
antagonists and that the one-year ulcer recurrence rate in patients
treated with antibiotics was significantly less than patients treated
with H2 receptor antagonists.  These data further support H. pylori
as a pathogen and suggest that H. pylori plays an important role in
duodenal ulcer recurrence.
 
Although the association of H. pylori and duodenal ulcer and
gastritis is well established, the relationship of  Helicobacter
pylori and gastric cancer is less certain. In a case control study,
several researchers have demonstrated that patients with gastric
lymphoma were more likely to be infected with H. pylori than their
matched controls. In addition, other investigators have shown that
patients with mucosa associated lymphoid tissue (MALT) lymphoma were
found to have H. pylori.  Although infection of H. pylori is
suggestive of a causative role in the etiology of gastric cancer and
lymphoma, more studies are needed to determine the true role of H.
pylori in gastric carcinogenesis.
 
Research Objectives and Scope
 
This RFA is designed to support basic and clinical research on the
biology of H. pylori and pathogenesis so that effective diagnostic
modalities and treatment interventions can be developed.  Relevant
topics of research include, but are not limited to the following:
 
o  Epidemiologic studies and clinical studies describing modes of
transmission, risk factors for infection, particularly in children
and minority populations.  Studies on the relationship between
environmental isolates obtained from infected individuals in an area
may provide insight into the regional variability of the H. pylori
infection.
 
o  Identification of cofactors in Helicobacter species that
contribute to biological carcinogenesis.
 
o  Identification of virulence factors of the organism in different
ethnic populations.
 
o  Definitions of genetic markers as they relate to disease
expression.
 
o  Investigation of the role of components of the epithelial barrier
(i.e., mucin, epidermal growth factor, transforming growth factors,
prostaglandin, and phospholipids) in the development of gastric
neoplasia.
 
o  Investigations of the molecular events in the etiology of gastric
cancer in relationship to DNA damage in gastric epithelium.
 
o  Identification of biomarkers of the different strains of H. pylori
which may be related to disease expression and outcome of infection
in different population groups.
 
o  Identification of mechanisms of infection and how resistance to
antibiotics occurs. Identify risk factors for H. pylori treatment
failures, and the rate of recrudescence versus reinfection with new
strains of H. pylori.
 
The above topics of research should not limit investigators from
developing other topics which are relevant to the goals of this RFA.
 
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
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
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rational and justification is provided
that inclusion is inappropriate with  respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 4928 of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Population) which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-1453), and reprinted
in the NIH GUIDE FOR GRANTS AND CONTRACTS Volume 23, Number 11, March
18, 1994.
 
Investigators may also obtain copies from the program staff or
contact person listed under INQUIRIES.  Program staff may also
provide additional relevant information concerning the policy.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by March 21, 1997, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.
 
Although letter of intent is not required is not binding, and does
not enter into the review of a subsequent application, the
information that it contains allows NIDDK staff to estimate the
potential review workload and avoid conflict of interest in the
review.
 
The letter of intent is to be sent to:
 
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 6AS 37-F - MSC6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-8885
FAX:  (301) 480-3505
 
APPLICATION PROCEDURES
 
Applications are to be submitted on the grant application form PHS
398 (rev. 5/95).  Application kits are available at most
institutional offices of sponsored research, or may be obtained from
the Division of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone 301-435-0714, email:
asknih@odrockm1.od.nih.gov.
 
The RFA label available in the PHS 398 application form must be
affixed to the bottom of the face page.  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.
 
Applications for the FIRST Award (R29) must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST Award (R29) applications submitted without the
required number of reference letters will be considered incomplete
and will be returned without review.
 
Submit a signed, typewritten original of the application, including
the Checklist, and three signed, exact photocopies, in one package
to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/carrier service)
 
At time of submission, two additional copies of the application must
also be sent under separate cover to:
 
Chief, Review Branch
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Natcher Building, Room 6AS-37F
45 Center Drive MSC 6600
Bethesda, MD  20892-6600
 
Applications must be received by April 22, 1997.  If an application
is received after that date, it will be returned to the applicant.
The DRG 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.  However, it
is allowable to submit the same project as both an R01 and as a
component project of a P01.  The DRG will not accept any application
that is essentially the same as one already reviewed.  This does not
preclude the submission of substantial revisions of applications
previously reviewed.  Such applications must not only include an
introduction addressing the previous critique but also be responsive
to this RFA.
 
REVIEW CONSIDERATIONS
 
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 NIDDK in accordance with NIH peer review
procedures.  As part of the initial merit review, all applications
will receive a written critique and undergo a process in which only
those applications deemed to have the highest scientific merit,
generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the appropriate advisory council/board.
 
Review Criteria
 
o  scientific/technical merit criteria specific to the objectives of
the RFA;
 
o  scientific, technical, or medical significance and originality of
proposed research;
 
o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
 
o  qualifications and research experience of the Principal
Investigator and staff, particularly but not exclusively in the area
of the proposed research;
 
o  availability of resources necessary to perform the research;
 
o  appropriateness of the proposed budget and duration in relation to
the proposed research; and
 
o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.
 
The initial review group will also examine the provisions for the
protection of human and animal subjects, and the safety of the
research environment.
 
AWARD CRITERIA
 
The anticipated date of award is September 30, 1997. Award criteria
will include the scientific merit of the application as determined by
peer review, availability of funds, and programmatic priorities.
 
Schedule
 
Letter of Intent Receipt Date:  March 21, 1997
Application Receipt Date:       April 22, 1997
Initial Review:                 June-July 1997
Second Level Review:            September 17-18, 1997
Anticipated Award:              September 30, 1997
 
INQUIRIES
 
Written and telephone inquiries for this RFA and the opportunity to
clarify any issues or questions from potential applicants are
encouraged.
 
Direct inquiries regarding programmatic issues to:
 
Frank A. Hamilton, M.D., M.P.H.
Division of Digestive Diseases and Nutrition
National Institute of Diabetes and Digestive and Kidney Diseases
Natcher Building, Room 6AN-12B
Bethesda, MD  20892-6600
Telephone:  (301) 594-8877
FAX:  (301) 480-8300
Email:  hamiltonf@ep.niddk.nih.gov
 
Appasaheb Patel, Ph.D.
Division of Cancer Epidemiology and Genetics
National Cancer Institute
6130 Executive Plaza, Suite 535, MSC 7395
Bethesda, MD  20892-7395
Telephone:  (301) 496-9600
FAX:  (301) 402-4279
Email:  patela@epndce.nci.nih.gov
 
Dennis Lang, Ph.D.
Enteric Diseases Program
National Institute of Diabetes and Digestive and Kidney Diseases
6003 Executive Boulevard, Room 3A21
Bethesda, MD  20892
Telephone:  (301) 496-7051
FAX:  (301) 402-1456
Email:  DL73V@nih.gov
 
Inquiries regarding fiscal matters may be directed to:
 
Mrs. Nancy Dixon
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
Natcher Building, Room 6AN-44C
Bethesda, MD  20892
Telephone:  (301) 594-8854
FAX:  (301) 480-3504
Email:  dixonn@ep.niddk.nih.gov
 
Mr. R.E. Hawkins, Jr.
National Cancer Institute
6120 Executive Boulevard, Suite 243, MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, Ext 213
Email:  hawkinsr@gab.nci.nih.gov
 
Louise Kreh
Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases
6003 Executive Boulevard, Room 4B27
Bethesda, MD  20892
Telephone:  (301) 496-7075
FAX:  (301) 402-5065
Email:  LK5K@NIH.GOV
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance Nos. 93-848, 93.393, and 93.856 .  Awards are made under
authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under PHS grants policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74.  This program is not
subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.
 
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-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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