Multimodal Investigation of the Neuroprotective Effects of Resveratrol (MINER)

NCT03665740 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: GW160050
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Since their return from military service in the 1990-1991 Gulf War, many Veterans have been affected by debilitating symptoms that are not easily explained. A leading hypothesis states that the combination of exposure to toxic chemicals and environmental stressors are responsible for a cluster of debilitating symptoms known as Gulf War Illness (GWI). Research has found that over-the-counter antioxidant supplements such as resveratrol may reverse the damage that causes these debilitating symptoms. Resveratrol is a nutrient found abundantly in the skin of red grapes that is known to have robust antioxidant and anti-inflammatory properties. The investigators predict that resveratrol treatment will improve memory issues, difficulties with thinking and mood problems in Veterans with GWI and that resveratrol will do so with minimal risk.

Conditions

Gulf War Illness

Keywords

Gulf War Illness; Chronic Multisymptom Illness; Antioxidants; Resveratrol; Gulf War Syndrome

Outcome Measures

Primary Outcomes (3)

• Change from baseline in Cognitive Function

  CVLT-II: measure of cognitive functioning and memory

  Baseline & Post (week 26)

• Change from baseline in Mood

  Beck Depression Inventory II

  Baseline, Mid (week 13) and Post (week 26)

• Change from baseline in Daily Functioning

  WHODAS 2.0: measure of disability and global health

  Baseline and Post (week 26)

Secondary Outcomes (2)

• Change from baseline in Structural MRI Scans

  Baseline & Post (Week 26)

• Change from baseline in Diffusion Tensor Imaging

  Baseline & Post (Week 26)

Other Outcomes (1)

• Change from baseline in Pro-inflammatory cytokines

  Baseline & Post (Week 26)

Study Arms (2)

Resveratrol

EXPERIMENTAL

Doses of resveratrol at 500 mg will begin with a dose titration period. In order to reach a maximum dose of 2000 mg for the resveratrol, titration will begin at 500 mg for 6 weeks, then increased to 1000 mg for 6 weeks and increased to 1500 mg for 6 weeks and increased to 2000 mg for the remaining 6 weeks on treatment.

Drug: Resveratrol

Placebo

PLACEBO COMPARATOR

Doses of placebo at 500 mg will begin with a dose titration period. In order to reach a maximum dose of 2000 mg for the placebo, titration will begin at 500 mg for 6 weeks, then increased to 1000 mg for 6 weeks and increased to 1500 mg for 6 weeks and increased to 2000 mg for the remaining 6 weeks on treatment

Drug: Resveratrol

Interventions

Resveratrol DRUG

resveratrol is an OTC supplement

Placebo; Resveratrol

Eligibility Criteria

• Age: 44 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Served on active military duty and deployed to the Persian Gulf region August 1990 - July 1991;
• English speaking and able to understand the consent form and study questionnaires;
• Willing and able to be randomized to treatment and to commit to a 26-week study;
• Men and women between the ages of 44 to 68 (the number of 1990-1991 Gulf War Veterans who are older than 68 dramatically decreases because many of those with GWI have died prematurely);
• Meet the Kansas case definition for the diagnosis of GWI as well as the more inclusive CDC definition
• Stabilization on any psychiatric medication (≥3 months on selective serotonin reuptake inhibitor or monoamine oxidase inhibitor, ≥1 month on anxiolytic or beta-blockers);

You may not qualify if:

• Unstable or poorly controlled diabetes type II (HbA1C \>9.0);
• Cancer;
• Lifetime diagnosis of schizophrenia or bipolar disorder or a history of psychiatric hospitalization for, or current diagnosis (i.e., the past 6 months) of substance dependence;
• Major depressive disorder or posttraumatic stress disorder requiring hospitalization;
• Significant CNS disease including TIAs or stroke, dementia, syncopal episodes, severe head trauma, multiple sclerosis;
• Serious or advanced heart disease or clinically relevant abnormal electrocardiogram (ECG) or postural hypotension;
• Untreated sleep apnea or body mass index (BMI) placing patients at risk for undiagnosed sleep apnea (BMI≥35 kg/m2);
• Subjects with renal insufficiency or chronic renal disease defined by national Kidney Foundation Disease Outcome Quality Initiative criteria (2000) with a GFR less than or equal to 90 mL/min/1.73m2. Laboratory monitoring of CR and Bun and eGFR will be obtained at baseline and prior to each titration and at study end or early termination. If Cr and Bun increase above upper limit of normal and eGFR drops to \<45 or more than 35% the study drug will be discontinued and a nephrology consult will be ordered;
• Liver enzymes \>3 times normal on 3 consecutive laboratory tests; evidence of significant hepatocellular injury as evidenced by elevated serum levels of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal (ULN); total or indirect bilirubin greater than 1.2 x ULN; alkaline phosphatase greater than 1.5 x ULN; prothrombin time (PT) as INR greater than 2.4 x ULN; or albumin less than 1 times the lower limit of normal (LLN) at baseline. Resveratrol is only anticipated to affect LFTs indirectly, by slowing statin metabolism. Persistent significant elevation of amino transferases are defined as \>3x normal of normal upper limit on 2 consecutive measurements. Under the conditions of high dose statin therapy, it is typically addressed by temporarily stopping statin administration, then slowly titrating the dose back up under careful observation. Failure to reduce aminotransferase levels after the temporary cessation of statins (and a third LFT measurement is taken) would necessitate cessation of resveratrol treatment.
• Use of cytochrome P450 3A4 substrates with high risk of toxicity (e.g., terfenadine, cisapride, astemizole, disopyramide, amiodarone, dronedarone, colchicine, cyclosporine, quinidine, pimozide, cisapride, amlodipine, felodipine, nicardipine, nifedipine, nisoldipine, nitrendipin, nimodipine and verapamil);
• Use of blood thinners (e.g., Coumadin);
• Use of resveratrol-containing supplements.
• General medical conditions that would prevent the participant from completing MRI scanning (active seizure disorder, dementia, active back or muscle spasms);
• Positive MRI safety screen for metal or history of penetrating head or eye wound without subsequent radiological evidence that the wound is metal-free;
• Participants that are (were) welders or that have had metal surgically removed from their eyes without radiological evidence that the wound is metal-free;

Sponsors & Collaborators

• VISN 17 Center of Excellence: lead
• Texas A&M University: collaborator
• Baylor University: collaborator
• KR Love Quantitative Consulting and Collaboration: collaborator

Study Sites (1)

VISN 17 Center of Excellence for Research on Returning War Veterans

Waco, Texas, 76711, United States

RECRUITING

Related Links

• Website for the VISN 17 Center of Excellence for Research on Returning War Veterans

MeSH Terms

Conditions

Persian Gulf Syndrome

Interventions

Resveratrol

Condition Hierarchy (Ancestors)

Occupational Diseases; War-Related Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Stilbestrols; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polyphenols; Phenols

Study Officials

• Dena Davidson, Ph.D.

  VISN 17 Center of Excellence

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tabitha Alverio, M.A.

CONTACT

254.297.3259; Tabitha.Alverio@va.gov

Laura Constable, M.A.

CONTACT

254.297.3954; Laura.Constable@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Model Details: Randomized Double-blind Placebo controlled, intent-to-treat

Study Record Dates

• First Submitted: August 8, 2018
• First Posted: September 11, 2018
• Study Start: August 1, 2018
• Primary Completion: August 31, 2022
• Study Completion: August 31, 2022
• Last Updated: September 11, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)