Department of Defense Grant for Gulf War Illness, Clinical Evaluation

The FY20 GWIRP Clinical Evaluation Award supports translation of validated GWI research, including qualified and replicated preclinical findings, to a Gulf War Veteran population. The Clinical Evaluation Award targets the Verification phase of the research pipeline as outlined in Section II.A.2. Statistically powered biomarker trials with the potential to validate use of biomarkers as clinical endpoints or proof-of-concept intervention trials (e.g., pilot, first in human, Phase I-IIa) are encouraged under this funding opportunity. Large-scale clinical biomarker research and biomarker trials meet the intent of this funding opportunity. While proof-of-concept intervention trials of treatments repurposed from other disorders sharing GWI symptomatology will be considered (with appropriate rationale), the FY20 GWIRP encourages studies that translate qualified results from the GWI research community.

Funding from this award mechanism must support research in a Gulf War Veteran population. Proof of availability and access to necessary cohort(s) and/or critical reagents must be provided.

Gulf War Veteran Recruitment: Applicants are strongly encouraged to consider the outreach and recruitment best practices described online at https://cdmrp.army.mil/gwirp/pdfs/General%20_Guidance_for_Gulf_War_ Veteran_Outreach_and_Recruitment.pdf.

FY20 GWIRP Clinical Evaluation Award Areas of Emphasis: The FY20 GWIRP Clinical Evaluation 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 Overarching Challenges.

 Clinical translation of treatments that have shown positive impact on GWI

 Clinical translation of biological indicators 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 widespread pain

○ Chronic debilitating fatigue

○ Gastrointestinal effects including dietary intolerances, gastroesophageal reflux disease (GERD) and functional gastrointestinal disorders (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 gastrointestinal tract) that contributes to malfunction in several physiological systems

 Clinical validation of molecular signatures (e.g., genomic, proteomic, metabolic, and epigenetic) underlying symptoms and the grouping of symptom sets based on common underlying pathobiology

 Clinical investigation of comorbidities, mortality, sex or ethnic differences

The requested budget must be commensurate with the phase and size of the trial proposed. Refer to Section II.D.5, Funding Restrictions for detailed funding information.

Biorepository Contribution Option: In FY17, the GWIRP awarded infrastructure support for a Gulf War Illness 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 Clinical Evaluation Award offers a 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. Applicants interested in collaborating with this network should refer to the GWIRP Supported Initiatives on the GWIRP website.

Clinical Consortium Collaboration Option: In FY17, the GWIRP awarded a Clinical Consortium Award to create a network of institutions focused on designing and executing Phase I and II clinical trials. The Gulf War Illness Clinical Trials and Interventions Consortium (GWICTIC) has now been established to investigate promising therapeutics for GWI. Applicants to the FY20 GWIRP are encouraged to make use of the established infrastructure of the GWICTIC, such as recruitment networks, existing protocols, Common Data Elements (CDEs), and data management procedures. Clinical Consortium Collaboration Option applications shall adhere to the GWICTIC policies and procedures with respect to biospecimens and data and therefore are not eligible to also submit under the Biorepository Contribution Option. A letter of collaboration from the GWICTIC is required, outlining the services that will be shared to bring value to the Government. The FY20 GWIRP Clinical Evaluation Award offers a Clinical Consortium Collaboration 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.

Activities not supported under this Program Announcement include:

 Studies focusing on psychiatric disease or psychological stress as the primary cause of GWI or implementation of care guidelines placing significant emphasis on psychiatric pathologies or psychiatric remedies.

 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 ALS Research Program (see https://cdmrp.army.mil/alsrp).

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 Clinical Evaluation Award will not exceed $1,500,000. If applying under the Biorepository Contribution Option, direct costs will not exceed $1,520,000. If applying under the Clinical Consortium Collaboration Option, direct costs will not exceed $1,700,000. Clinical Consortium Collaboration Option applications shall adhere to the GWICTIC policies and procedures with respect to biospecimens and data and therefore are not eligible to also submit under the Biorepository Contribution Option. 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 $4,800,000 to fund approximately two Clinical Evaluation 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.