Department of Defense: Gulf War Illness Research Advancement Award

The FY20 GWIRP Research Advancement Award supports applied research in GWI that is aimed at continued expansion and validation of markers and treatments that are supported by evidence in the GWI field. The Research Advancement Award targets the Qualification phase of the research pipeline as outlined in Section II.A.2.

Preliminary Data: Inclusion of preliminary data in the field of GWI and other supporting information is required. The project should include a well-formulated, testable hypothesis based on existing evidence in the GWI field that holds translational potential.

Impact: Applications must articulate how results will lead to a clinical impact for Veterans with GWI even if a clinical impact is not an immediate outcome. All applications must focus on features of GWI and Veterans of the 1990-1991 Gulf War affected by GWI. The application should clearly and explicitly articulate the project’s potential impact on GWI.

The types of activities supported include, but are not limited to, expansion of limited data on candidate markers, mechanistic targets; therapeutics and interventions; validation and advanced research on druggable mechanistic targets, identification and development of leading compounds, and collection of preclinical data for repurposing an existing approved drug or for new Investigational New Drug (IND) application submissions to the U.S. Food and Drug Administration (FDA). Applicants proposing to test FDA-approved drugs in animal models for efficacy must explain why preclinical testing is required prior to clinical pilot trials in humans.

FY20 GWIRP Research Advancement Award Areas of Emphasis: The FY20 GWIRP Research Advancement Award has a special interest in the exploration of the topics listed below. Applicants are not restricted to this list and may propose studies in any other GWI research area relevant to the mission of the GWIRP and in the context of the FY20 GWIRP Overarching Challenges.

• Replication and validation of treatments that have shown positive impact on GWI

• Replication and/or validation of the causes of and treatment targets for dysregulated biological system function. Emphasis should be placed on:

○ Cognitive difficulties to include memory deficits, mood and behavior disturbances

○ Non-restorative sleep or sleep disturbances

○ Chronic wide-spread pain

○ Chronic debilitating fatigue

○ Gastrointestinal effects including dietary intolerances, GERD and FGIDs

○ Sinus and respiratory effects

○ Headaches

○ Dermatological issues

○ Neurological dysfunction (central, peripheral, autonomic, and/or neuromuscular)

○ Immune system dysfunction

○ Endocrine, exocrine, and/or excretory system dysfunction, with special attention to kidney and liver (e.g. Cytochrome P450 abnormalities)

○ Microbiome variants

○ The impact of stresses (e.g. exertion, immune challenge) on the severity and duration of the symptoms

○ Disordered system crosstalk (e.g., immunological dysfunction that alters the nervous system, autonomic dysfunction that impacts functioning of the GI tract) that contributes to malfunction in several physiological systems

• Continued investigation into molecular signatures (e.g. genomic, proteomic, metabolic, and epigenetic) underlying symptoms and the grouping of symptom sets based on common underlying pathobiology

• Investigation of comorbidities, mortality, sex or ethnic differences

Biorepository Contribution Option: In FY17, the GWIRP awarded infrastructure support for a GWI Biorepository. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI has now been established for the retention and distribution of Gulf War Veteran biospecimens and/or data related to GWI research. Applicants to the FY20 GWIRP are encouraged to contribute Gulf War Veteran biospecimens and data to this repository network. The FY20 GWIRP Research Advancement Award offers a nested Biorepository Contribution Option with higher levels of funding for qualified applications as described in Section II.D.5, Funding Restrictions. See Attachment 10, Options Statements for additional submission requirements. For additional details about BBRAIN, refer to the section below titled, Access to Data and/or Previously Collected Biospecimens from Veterans of the 1990-1991 Gulf War.

Activities not supported under this Program Announcement include:

• Investigations involving derivation of GWI diagnostic biomarkers from animal models.

• Trials of FDA-approved drugs in animals if there exists sufficient evidence or rationale to support clinical trials in humans instead.

• Studies focusing on psychiatric disease or psychological stress as the primary cause of GWI.

• Applications focusing on amyotrophic lateral sclerosis (ALS) research. However, applications that focus on GWI symptomatology may include Gulf War Veterans with ALS if the latter disorder is included in the study’s GWI case definition. For those interested in pursuing ALS-focused studies, the CDMRP offers funding opportunities through the Amyotrophic Lateral Sclerosis Research Program (see https://cdmrp.army.mil/alsrp).

• Clinical trials. A clinical trial is defined as a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes. Investigators interested in clinical trials should consider applying under the FY20 GWIRP Clinical Evaluation Award or Therapeutic/Biomarker Trial Award (Funding Opportunity Numbers: W81XWH-20-GWIRP-CEA and W81XWH-20-GWIRP-TBTA, respectively). For information about these award mechanisms, see https://cdmrp.army.mil/funding/gwirp.

The types of awards made under the Program Announcement will be assistance agreements. An assistance agreement is appropriate when the Federal Government transfers a “thing of value” to a “state, local government,” or “other recipient” to carry out a public purpose of support or stimulation authorized by a law of the United States instead of acquiring property or service for the direct benefit and use of the U.S. Government. An assistance agreement can take the form of a grant or cooperative agreement. The level of involvement on the part of the Department of Defense (DoD) during project performance is the key factor in determining whether to award a grant or cooperative agreement. If “no substantial involvement” on the part of the funding agency is anticipated, a grant award will be made (31 USC 6304). Conversely, if substantial involvement on the part of the funding agency is anticipated, a cooperative agreement will be made (31 USC 6305), and the award will identify the specific substantial involvement. Substantial involvement may include, but is not limited to, collaboration, participation, or intervention in the research to be performed under the award. The award type, along with the start date, will be determined during the negotiation process.

The anticipated direct costs budgeted for the entire period of performance for an FY20 GWIRP Research Advancement Award will not exceed $625,000. If applying under the Biorepository Contribution Option, direct costs will not exceed $645,000. Refer to Section II.D.5, Funding Restrictions, for detailed funding information.

Awards will be made no later than September 30, 2021. For additional information refer to Section II.F.1, Federal Award Notices.

The CDMRP expects to allot approximately $3,000,000 to fund approximately three Research Advancement Award applications. Funding of applications received is contingent upon the availability of Federal funds for this program as well as the number of applications received, the quality and merit of the applications as evaluated by scientific and programmatic review, and the requirements of the Government. Funds to be obligated on any award resulting from this funding opportunity will be available for use for a limited time period based on the fiscal year of the funds. It is anticipated that awards made from this FY20 funding opportunity will be funded with FY20 funds, which will expire for use on September 30, 2026.