Full Text DA-96-003 NOVEL PHARMACOTHERAPIES FOR COCAINE AND OTHER PSYCHOSTIMULANT DEPENDENCE NIH GUIDE, Volume 24, Number 41, December 1, 1995 RFA: DA-96-003 P.T. 34 Keywords: Drugs/Drug Abuse Chemotherapeutic Agents National Institute on Drug Abuse Letter of Intent Receipt Date: January 19, 1996 Application Receipt Date: February 21, 1996 PURPOSE The purpose of this Request for Applications (RFA) is to encourage clinical testing of innovative and non-traditional pharmacotherapies for treatment of cocaine/psychostimulant (amphetamines) dependence. Two types of medications will be considered: (1) traditional pharmacotherapies addressing novel neurochemical mechanisms (beyond classical biogenic amines or compounds previously extensively tested); (2) non-traditional (alternative) pharmacotherapies selected to restore brain homeostasis or to repair/compensate for existing neurological/neurochemical deficits in chronic psychostimulant abusers (e.g., special nutritional factors, amino acids, neurotransmitter precursors, hormones, antihormones, supplements, etc.). Special emphasis will be put on testing natural compounds with very low or no toxicity, which could be potentially also utilized for treatment of children and pregnant women. Investigators should study the safety and efficacy of novel medications in either relapse prevention in detoxified cocaine/psychostimulant dependent participants or reduction of drug use. The primary focus will be on relapse prevention. Applications will be also required to assess the impact of investigational agent on HIV risk behaviors. Applications that propose to evaluate compounds already extensively studied in psychostimulant dependence (traditional medications that act at dopamine, noradrenaline, or serotonin systems, or carbamazepine, etc.) will not be considered responsive. 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 RFA, Novel Pharmacotherapies for Cocaine and Other Psychostimulant Dependence, is related to the priority areas of alcohol and other drugs. 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, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Racial/ethnic minority individuals, women and persons with disabilities are encouraged to apply as principal investigators. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). International collaborative studies, which must include a U.S. principal investigator, will also be considered. For example, if the investigational compound is not available on the U.S. market, but is available in European or Asian pharmacopeias, the pilot studies may be conducted in a foreign country. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) research project grant (R01), FIRST (29) award, exploratory/developmental grant (R21), and small grant (R03). Research grants are awarded to institutions on behalf of Principal Investigators who have designed and will direct a specific project or set of projects. Because the small grants and FIRST awards have special eligibility requirements, application formats, and review criteria, applicants are strongly encouraged to consult with the program staff (listed under INQUIRIES) and to obtain the appropriate additional guidelines/announcements for those grant mechanisms. FUNDS AVAILABLE It is anticipated that approximately $4 million will be available to support projects submitted under this RFA. Because the nature and scope of the research proposed in response to this RFA may vary, the size of an award will vary also. However, it is anticipated that between 12 and 20 new awards will be made under this RFA. About 70 percent of funds will be directed toward projects testing novel medications for relapse prevention, and about 30 percent toward projects testing effects of novel medications on reduction of drug use. RESEARCH OBJECTIVES Recent findings in clinical and preclinical neurosciences reveal complex biological determinants underlying psychostimulant dependence. These include psychopathological, neuroanatomical, pathophysiological, neuroadaptive, neurochemical, and hormonal factors, and may involve a variety of nutritional, environmental and toxicological substrates as underlying causes of drug addictions. Psychostimulant dependence is associated with various degrees of neuropathology and significant comorbidity with other neurological and psychiatric disorders, including attention and mood disorders, hypodopaminergia, hyposerotonergia, and hypofrontalism, manifested in perfusion and metabolic/bioenergetic deficits, among others. The bioenergetic deficits induced by psychostimulants may promote brain aging and facilitate neurodegenerative disorders in chronic psychostimulant abusers. Rational pharmacological interventions in these biological/pathological substrates could be effective in treating psychostimulant dependence. Moreover, recent reemergence, reported therapeutic success and safety of non-traditional pharmacotherapies, including medically designed nutrition, supplements, vitamins, amino acids, hormones and other natural compounds, in treating variety of chronic disorders suggest exploration of non-traditional treatments as potential therapies for cocaine/psychostimulant dependence. Such natural therapies, designed to normalize brain functions may be more acceptable to treatment-seeking addicts, who often refuse to be treated with conventional medications, and be more beneficial than traditional pharmacotherapies, which often produce undesirable side effects. It is expected that such therapies may be safe enough to be used for treatment of addicted children, adolescents or pregnant women. The main objective of this RFA is to encourage clinical evaluation of: (1) novel traditional medications with compounds and classes of compounds previously not studied in clinical trials to treat psychostimulant dependence, and; (2) non-traditional pharmacotherapies, in relapse prevention designs in detoxified cocaine/stimulant dependent participants, or reduction of drug use in psychostimulant addicts. The hypothesis and rationale for testing these novel medications should address one or more of the following research/clinical aspects: 1. the persistent neurochemical imbalance and/or neuroadaptive/neuropathological changes that have been described in cocaine/psychostimulant dependent individuals or in animals treated chronically with stimulants; 2. the pharmacological intervention in neurochemical and psychological factors contributing to vulnerability to stimulant dependence (e.g., attention deficit hyperactivity disorder, post-traumatic stress disorder); 3. the hormonal abnormalities in cocaine/stimulant dependent persons; 4. the biochemical mechanism relevant for behavioral outcomes for cocaine dependence (e.g., drug craving); 5. neurochemical factors involved in expression of euphorigenic and dependence-producing effects of psychostimulants; 6. neurochemical factors responsible for persistent anhedonia, depression, and anxiety, associated with psychostimulant withdrawal and accompanying abstinence in chronic psychostimulant abusers; 7. the availability of open clinical trial data or promising preclinical results; 8. other scientific or clinical rationales. Investigators are encouraged to study novel medications, yet untested for treatment of psychostimulant dependence (including those not approved in the U.S., but approved in European and Asian pharmacopeias) as well as a variety of nutritional factors, supplements, and naturally occurring substances, rationally selected to compensate for biochemical and functional deficits reported in stimulant addicts (e.g., apparent deficiency of biogenic amines, an imbalance in endogenous opioid peptides and other neurotransmitters) and to restore the brain homeostasis in psychostimulant dependent individuals. We are soliciting applications that test the hypothesis that correcting for persistent or permanent neuropathologies that are associated with psychostimulant dependence with novel pharmacotherapies may be effective in treating this disorder. Possible examples of such treatments include: precursors of biogenic amines and other neurotransmitters, vitamins and supplements that modify neurotransmitter metabolism and energy metabolism, and herbs of known therapeutic profile. Examples of potential therapeutic herbs may include: Ginkgo Biloba, Kudzu, Ginseng, Gotu Cola, and Kelp, among others. Encouraged also are pharmacological and natural interventions in hormonal systems (e.g., hypothalamo-pituitary-adrenal axis, hypothalamo-pituitary-gonadal axis, thyroid system, endogenous opioid peptides) that have been shown to play a role in drug dependence. Medications designed to improve deficient brain circulation, energy and phospholipid metabolism, and cognition, will be also considered along with rational combinations of treatments. Because no pharmacotherapy is expected to be optimally effective without concurrent behavioral therapy, adjunct therapies may concentrate on psychological, behavioral processes such as motivation building, relapse prevention skills, coping skills, skills for utilization of alternative reinforcers, as well as meditation, or imagery. Drug dependence encompasses both physical and psychological symptomatology; therefore, developing and testing integrative approaches for treatment of psychostimulant dependence is encouraged (i.e., treatments that stress pharmacotherapy, psychological support, behavioral and nutritional adjustments, and social adaptations). In addition to testing potential treatments that affect primary psychostimulant dependence, applications are encouraged to evaluate novel treatments for disorders comorbid with drug dependence; these include anxiety, depression, anhedonia, attention deficit and cognitive impairments, antisocial behavior, post-traumatic stress disorder, and other diagnoses that may contribute to continued psychostimulant abuse and relapse. The proposed studies should test the safety and efficacy of novel therapeutic approaches in rigorously designed and executed clinical trials to prevent relapse in persons detoxified from cocaine/psychostimulant dependence or to reduce drug use in addicts. Identified treatment modalities may be assessed in clinical pharmacologic-therapeutic paradigms (laboratory clinical assessments) and/or in phase I/II clinical trials that meet accepted standards for Good Clinical Practice (GCP) guidelines established by FDA (21 CFR). Because most psychostimulant abusers also co-abuse other substances (alcohol, benzodiazepines, opiates), evaluation of the impact of proposed new therapies on the use of the above drugs, in addition to psychostimulants, will be also required. Applications will be also required to assess impact of the investigational agent on HIV risk behaviors. Proposals must seek and obtain IRB review and approval prior to submission or review of the application. SPECIAL REQUIREMENTS The exploratory, developmental (R21) and Small Grant (R03) applications are limited to two years, are non-renewable, and are limited in direct cost amount per year (R03, $50,000; R21, $90,000). The R03 mechanism is intended for new, inexperienced investigators and both are intended for established investigators exploring new areas or departing from their usual research topics. There are special requirements for these mechanisms. An applicant intending to apply for them under this RFA should contact the named program person in the INQUIRIES section for further information. 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 subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale 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 492B 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 Populations), which have been in effect since 1990. This new policy contains some new 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 14508-14513) and reprinted in the NIH Guide for Grants and Contracts of March 18, 1994, Volume 23, Number 11. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. This RFA requires that proposed studies conduct gender comparisons of clinical responses (side effects, efficacy, etc.) to the new medications and strongly encourages examination of menstrual cycle effects on the pharmacokinetics and pharmacodynamics of proposed new therapies. LETTER OF INTENT Prospective applicants are asked to submit, by January 19, 1996, a letter of intent that includes a descriptive title of the proposed research, the proposed mechanism of support, the telephone number of the Principal Investigator, the identities of other key personnel and participating institution, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIDA staff to estimate the potential review workload and to avoid conflict of interest review. The letter of intent is to be sent to: Director Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 FAX: (301) 443-0538 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grant Information, Division of Research Grants, National Institutes of Health, 6701 Rockledge Drive, Room 3032, MSC 7762, Bethesda, MD 20892-7762, telephone (301) 710-0267; email: girg@drgpo.drg.nih.gov. FIRST applications must include at least three sealed letters of reference attached to the Face Page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The RFA label in the form PHS 398 application kit must be affixed to the bottom of the original face page. Failure to use the RFA label and to follow instructions 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 in Item 2 of the face page and YES box marked. Submit a signed, typewritten original of the application, including Checklist, and three signed photocopies in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for overnight/courier service) At the time of submission, two additional copies of the application must also be sent to: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and for responsiveness by NIDA. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, it will be returned without review. Applications that are complete and responsive to the RFA will be evaluated for scientific/technical merit by an appropriate peer review group convened by NIDA in accordance with the review criteria stated below. As part of the initial merit review, a streamlined review will be used by the initial review group in which application will be determined to be competitive or noncompetitive based on their scientific merit relative to other applications received in response to this RFA. Applications determined to be non-competitive will be withdrawn from further consideration and the Principal Investigator and the official signing for the application will be notified. 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 principal investigator could be included with the application. Review Criteria o merit, 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 or proposed research; o availability of the 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. o adequacy of plans regarding assessment of effects of proposed new medications on HIV risk behaviors. Plans for recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human subjects and the safety of the research environment. AWARD CRITERIA Applications recommended for further consideration by an appropriate Advisory Council will be considered for funding on the basis of overall scientific and technical merit of the proposal as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. Schedule Letter of Intent Receipt Date: January 19, 1996 Application Receipt Date: February 21, 1996 Initial Review Date: April 1996 Advisory Council Date: May 1996 Earliest Start Date: July 1996 INQUIRIES Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Maria Dorota Majewska, Ph.D. Medications Development Division National Institute on Drug Abuse 5600 Fishers Lane, Room 11A-55 Rockville, MD 20857 Telephone: (301) 443-3318 FAX: (301) 443-2599 Email: mm158w@nih.gov Direct inquiries regarding fiscal and grants management issues to: Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 5600 Fishers lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 Email: gfleming@aoada1.ssw.dhhs.gov AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public health Service Act, Section 301, and administered under PHS grants policies and federal regulations at Title 42 CFR 52 "Grants for Research projects", Title 45 CFR Part 74 & 92 "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects". Title 42 CFR part 2, "Confidentiality of Alcohol and Drug Abuse patient records" may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health System Agency review. Sections of the Code of Federal regulation are available in booklet form from the U.S. Government Printing Office. Grants must be administered in accordance with the PHS Grants Policy Statement (revised 4/94), which may be available from your office of sponsored research. The PHS strongly encourages all grant 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 of 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. .
Return to NIH Guide Main Index
Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
||||||||
Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files. |