IMMUNE-MEDIATED SENSORINEURAL HEARING LOSS

NIH Guide, Volume 22, Number 17, April 30, 1993



PA NUMBER:  PA-93-081



P.T. 34



Keywords:

  Communicative Disorders, Hearing 

  Hearing 

  Immunology 

  Epidemiology 



National Institute on Deafness and Other Communication Disorders



PURPOSE



The Division of Communication Sciences and Disorders, National

Institute on Deafness and Other Communication Disorders (NIDCD),

invites applications for the support of research addressing

immune-mediated sensorineural hearing loss.  The goal of this Program

Announcement (PA) is to stimulate both basic and clinical research

related to the etiology, diagnosis, and treatment of sensorineural

hearing loss related to immune mechanisms.



HEALTHY PEOPLE 2000



The Public Health Service (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 PA,

Immune-Mediated Sensorineural Hearing Loss, is related to the priority

areas of immunization and infectious diseases and diabetes and chronic

disabling diseases.  Potential applicants may obtain a copy of "Healthy

People 2000" (Full Report:  Stock No. 017-001-00474-0) or "Healthy

People 2000" (Summary Report:  Stock No. 017-001-00473-1) through the

Superintendent of Documents, Government Printing Office, Washington, DC

20402-9325 (telephone 202-783-3238).



ELIGIBILITY REQUIREMENTS



Applications may be submitted by domestic and foreign, for-profit and

non-profit organizations, such as universities, colleges, hospitals,

laboratories, units of state and local governments, and eligible

agencies of the Federal government. Foreign Institutions are not

eligible to apply for the First Independent Research Support and

Transition (FIRST) (R29) award.  Applications from minority individuals

and women are encouraged.



MECHANISM OF SUPPORT



Support mechanisms for this announcement include the individual

research project grant (RO1) and the FIRST (R29) award.



RESEARCH OBJECTIVES



Background



Idiopathic progressive sensorineural hearing loss affects thousands of

individuals each year.  There is a growing consensus that the immune

system may play an important role in the pathogenesis of this (these)

disorder(s).  This is based on the empirical observation that treatment

with immunosuppressive drugs may ameliorate or stabilize the hearing

loss.  Further, sensorineural hearing loss is often associated with the

presence of a defined autoimmune disease.  For example, auditory and

vestibular dysfunction has been reported in conjunction with

polyarteritis nodosa and systemic lupus erythematosus. Important

histopathological changes in the temporal bones of humans with

documented autoimmune diseases have also been found.



Factors inducing autoimmunity directed to the inner ear have been

postulated, but the etiology and pathogenesis of the disorder(s) are

not well understood.  Possible mechanisms include vasculitis of the

cochlear or vestibular blood supply, cross-reacting antibodies, or

antibodies directed against inner ear epitopes.  Genetic factors, such

as the inheritance of certain  human leukocyte antigens (HLA) have also

been proposed The availability of powerful laboratory techniques to

define immune responsivity, such as measurement of serum antibodies to

cochlear antigens with enzyme-linked immunosorbant assays (ELISA) and

lymphocyte transformation assay, have begun to provide the analytical

methods that may be required to detect altered immune status.  These

methods, combined with the development of animal models for autoimmune

sensorineural hearing loss (e.g., immunization of the guinea pig with

bovine or chick inner ear antigen), have contributed to the advancement

of this field to the point where concerted study of the problem of

immune-mediated sensorineural hearing loss is now possible.



Research Goals and Scope



There is a need to characterize immune responses in patients with

rapidly progressive sensorineural hearing loss; to develop animal

models that address the etiology and management of the disorder(s); to

determine the sensitivity, specificity, and efficacy of measures to

diagnose immune function abnormalities related to this disorder; and to

study the histopathologic characteristics of the ear during the

progression of this disease.  Areas of research on the etiology,

diagnosis, and treatment that would be responsive to this PA include,

but are not limited to:



o  definition of normal and abnormal immune responses in the inner ear;



o  identification of antigen(s) that induce immune reactions in the

inner ear;



o  investigation of the potential role of viral infections in immune

reactions producing inner-ear injury;



o  development and validation of animal models that address etiology;



o  determination of the site of immune-mediated sensorineural hearing

loss, due either to a specific organ-directed disease or to a

generalized systemic effect;



o  development and validation of a sensitive and specific test or

series of tests to diagnose immune-mediated sensorineural hearing loss;

and



o  assessment of the efficacy of therapeutic approaches  in the

amelioration of progressive immune-mediated sensorineural hearing loss.



STUDY POPULATIONS



SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH

POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL

RESEARCH STUDY POPULATIONS



NIH policy is that applicants for NIH clinical research grants and

cooperative agreements are required to include minorities and women in

study populations so that research findings can be of benefit to all

persons at risk of the disease, disorder or condition under study;

special emphasis must be placed on the need for inclusion of minorities

and women in studies of diseases, disorders and conditions which

disproportionately affect them.  This policy is intended to apply to

males and females of all ages.  If women or minorities are excluded or

inadequately represented in clinical research, particularly in proposed

population-based studies, a clear, compelling rationale must be

provided.



The composition of the proposed study population must be described in

terms of gender and racial/ethnic group.  In addition, gender and

racial/ethnic issues must be addressed in developing a research design

and sample size appropriate for the scientific objectives of the study.

This information must be included in the form PHS 398 in Sections 1-4

of the Research Plan AND summarized in Section 5, Human Subjects.

Applicants are urged to carefully assess the feasibility of including

the broadest possible representation of minority groups.  However, NIH

recognizes that it may not be feasible or appropriate in all research

projects to include representation of the full array of United States

racial/ethnic minority populations (i.e., Native Americans [including

American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks,

Hispanics).  The rationale for studies on single minority population

groups must be provided.



For the purpose of this policy, clinical research is defined as human

biomedical and behavioral studies of etiology, epidemiology, prevention

(and preventive strategies), diagnosis, or treatment of diseases,

disorders or conditions, including but not limited to clinical trials.



The usual NIH policies concerning research on human subjects also

apply.  Basic research or clinical studies in which human tissues

cannot be identified or linked to individuals are excluded.  However,

every effort should be made to include human tissues from women and

racial/ethnic minorities when it is important to apply the results of

the study broadly, and this should be addressed by applicants.



For foreign awards, the policy on inclusion of women applies fully;

since the definition of minority differs in other countries, the

applicant must discuss the relevance of research involving foreign

population groups to the United States' populations, including

minorities.



If the required information is not contained within the application,

the application will be returned.



Peer reviewers will address specifically whether the research plan in

the application conforms to these policies.  If the representation of

women or minorities in a study design is inadequate to answer the

scientific questions(s) addressed AND the justification for the

selected study population is inadequate, it will be considered a

scientific weakness or deficiency in the study design and reflected in

assigning the priority score to the application.



All applications for clinical research submitted to NIH are required to

address these policies.  NIH funding components will not award grants

or cooperative agreements  that do not comply with these policies.



APPLICATION PROCEDURES



Applications are to be submitted on the grant application form PHS 398

(rev. 9/91) and will be accepted at the standard application deadlines

as indicated in the application kit.  The receipt dates for

applications for AIDS-related research are found in the PHS 398

instructions.



Application kits are available at most institutional business offices

and may be obtained from the Office of Grants Inquiries, Division of

Research Grants, National Institutes of Health, Westwood Building, Room

449, Bethesda, MD 20892, telephone 301-710-0267.  The title and number

of the announcement must be typed in Section 2a on the face page of the

application.



The completed original application and five legible copies must be sent

or delivered to:



Division of Research Grants

National Institutes of Health

Westwood Building, Room 240

Bethesda, MD  20892**



REVIEW PROCEDURES



Applications will be reviewed for scientific and technical merit by

study sections of the Division of Research Grants, NIH, in accordance

with the standard NIH peer review procedures.  Following scientific

technical review, the applications will receive a second-level review

by the appropriate national advisory council.



AWARD CRITERIA



Applications will compete for available funds with all other approved

applications.  The following will be considered in making funding

decisions:



o  quality of the proposed project as determined by peer review,

o  availability of funds, and

o  program balance among research areas of the announcement.



INQUIRIES



Written and telephone inquiries concerning this PA are encouraged.  The

opportunity to clarify any issues or questions from potential

applicants is welcome.



Inquiries regarding programmatic issues may be addressed to:



Kenneth A. Gruber, Ph.D.

Division of Communication Sciences and Disorders

National Institute on Deafness and Other Communication Disorders

Executive Plaza South, Suite 400-B

6120 Executive Boulevard

Rockville, MD  20892

Telephone:  (301) 402-3458

FAX:  (301) 402-6251



Inquiries regarding fiscal matters may be addressed to:



Sharon Hunt

Division of Extramural Activities

National Institute on Deafness and Other Communication Disorders

Executive Plaza South, Suite 400-B

6120 Executive Boulevard

Rockville, MD  20892

Telephone:  (301) 402-0909

FAX:  (301) 402-6251



AUTHORITY AND REGULATIONS



This program is described in the Catalog of Federal Domestic Assistance

No. 93.173.  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.



.

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