Development of a Polyphenol-rich Dietary Preparation for Treating Veterans With Gulf War Illness

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Completed

CT.gov ID

NCT02915237

Collaborator

United States Department of Defense (U.S. Fed), Department of Veterans Affairs, New Jersey (U.S. Fed)

Enrollment

Location

Arms

29.5

Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Gulf War Illness (GWI) is a multi-symptom disorder that is characterized by complex traits such as fatigue, headaches, joint pain, insomnia, and memory problems. With no treatment for GWI currently available, there is an urgent need to develop novel interventions to alleviate major GWI clinical complications. Recent evidence highlights the potential value of flavonoids, a subclass of organic chemical called polyphenols abundantly found in some plants and common dietary preparations, in helping relieve clinical complications in Veterans with GWI. The overall goal is to test whether daily consumption of commercially available Concord grape juice, which is very Flavonoid-rich, is effective for treating cognitive deficits and chronic fatigue in Veterans with GWI.

Condition or Disease	Intervention/Treatment	Phase
Gulf War Illness	Dietary Supplement: Concord grape juice Dietary Supplement: Placebo Beverage	Phase 1/Phase 2

Detailed Description

Gulf War Illness (GWI) is a multi-symptom disorder that is characterized by complex traits. Clinical complications of GWI typically persist over long-term, cause significant pain and suffering, and interfere with the ability of affected Veterans to successfully integrate back into civilian society. There is no treatment for GWI and there is an urgent need to develop novel interventions either to resolve underlying GWI mechanisms, or to alleviate major GWI clinical complications.

Recent Evidence highlights the potential value of flavonoids, a subclass of organic chemical called polyphenols that are abundantly found in some plants and common dietary preparations may help alleviate chronic fatigue and preserve cognitive functions. Based on this, the overall goal is to test whether the potential efficacy of dietary supplementation with a commercially available flavonoid-rich product, alleviates clinical complications in Veterans with GWI. In particular, the researchers propose a randomized, double-blind, placebo-controlled Phase I/IIA study to test the feasibility and potential efficacy of Concord grape juice dietary supplementation to treat cognitive deficits and chronic fatigue in Veterans with GWI.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Development of a Polyphenol-rich Dietary Preparation for Treating Veterans With Gulf War Illness

Study Start Date :

Aug 1, 2016

Actual Primary Completion Date :

Jan 17, 2019

Actual Study Completion Date :

Jan 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low Dose - Concord grape juice Daily dietary supplementation with 4 oz. of a commercially available Concord grape juice.	Dietary Supplement: Concord grape juice Daily dietary supplementation with a commercially available Concord grape juice.
Experimental: Moderate Dose - Concord grape juice Daily dietary supplementation with 8 oz. of a commercially available Concord grape juice.	Dietary Supplement: Concord grape juice Daily dietary supplementation with a commercially available Concord grape juice.
Experimental: High Dose - Concord grape juice Daily dietary supplementation with 16 oz. of a commercially available Concord grape juice.	Dietary Supplement: Concord grape juice Daily dietary supplementation with a commercially available Concord grape juice.
Placebo Comparator: Low dose - placebo beverage Daily dietary supplementation with 4 oz. of a placebo beverage	Dietary Supplement: Placebo Beverage Daily dietary supplementation with a placebo beverage consisting of water, sugar, artificial flavoring and color that is formulated to look and taste like grape juice and have the same carbohydrate composition and energy load.
Placebo Comparator: Moderate Dose - placebo beverage Daily dietary supplementation with 8 oz. of a placebo beverage	Dietary Supplement: Placebo Beverage Daily dietary supplementation with a placebo beverage consisting of water, sugar, artificial flavoring and color that is formulated to look and taste like grape juice and have the same carbohydrate composition and energy load.
Placebo Comparator: High Dose - placebo beverage Daily dietary supplementation with 16 oz. of a placebo beverage	Dietary Supplement: Placebo Beverage Daily dietary supplementation with a placebo beverage consisting of water, sugar, artificial flavoring and color that is formulated to look and taste like grape juice and have the same carbohydrate composition and energy load.

Outcome Measures

Primary Outcome Measures

Brief Symptom Inventory (BSI) [6 months]
to assess safety and tolerability to treatment. The test is a 53-item self report scale that uses the 5 point Likert scale.
Patient Health Questionnaire-15 (PHQ-15) [6 months]
to assess safety and tolerability to treatment. The Patient Health Questionnaire 15 (PHQ 15) is a validated measure of somatic symptom severity in functional somatic syndromes (FSS). Scale ranges from 0-30 (mild to severe).
California Verbal Learning Test-Second Edition (CVLT-II) [6 months]
This test looks at cognitive functioning by assessing immediate recall and long-delayed recall.
The Chalder Fatigue Questionnaire [6 months]
The Chalder Fatigue Questionnaire assess chronic fatigue. Each of the 11 items are answered on a 4-point scale ranging from the asymptomatic to maximum symptomology

Secondary Outcome Measures

Wechsler Adult Intelligence Scale (WAIS-IV) [6 months]
The Digit Span subtest is a widely used measure of auditory attention that is well-normed and sensitive. The subtest has three parts - digits forward, backward, and sequencing.
the Conner's Continuous Performance Test-3 (CPT-3) [6 months]
The CPT-3 assist in clinical assessment of attention problems. The patient is instructed to press the space bar (or mouse button) immediately following the presentation of specific letters on screen. The test normally takes 14 minutes to administer.
the Trail Making Test (TMT) [6 months]
The TMT consists of two forms, parts A and B. This measure taps both simple graphomotor speed (Part A) and adds in a rapid set-shifting paradigm that taps executive functioning (Part B).
Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Block Design Subtest [6 months]
A tool for testing adult intelligence level.
the Stroop Test [6 months]
The Stroop Color and Word Test consists of a Word Page with color words printed in black ink, a Color Page with 'Xs' printed in color, and a color-Word Page with words from the first page printed in colors from the second page (the color and the word do not match). The respondent goes down each sheet reading words or naming the ink colors as quickly as possible within a time limit. The test yields three scores based on the number of items completed on each of the three stimulus sheets. An Interference score, which is useful in determining the individual's cognitive flexibility, creativity, and reaction to cognitive pressures also can be calculated.
Halstead Category Test [6 months]
This test takes approximately 30 minutes and consists of 120 items, presented visually. The participant must decipher the underlying principle of the stimulus set. Total number of errors will be used.
Brief Visuospatial Memory Test-Revised (BVMT-R) [6 months]
A tool to measure visuospatial learning and memory abilities.
Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) Digit Span Subtest [6 months]
Digit Span measures short-term auditory memory and attention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Gulf War Veterans deployed to the Persian Gulf theatre between August 1990 and August

GWI will be defined according to the Kansas Case Definition. The Kansas Case Definition identifies 6 symptom domains and requires endorsement of moderately severe and/or multiple symptoms in at least 3 of those domains. To meet the case definition, the Veterans must also indicate that each symptom first became problematic during or within one year of the Gulf War.

Exclusion Criteria:

Individuals not meeting the inclusion criteria for Gulf War deployment and definition of GWI, or with conditions that might interfere with their ability to report their symptoms (e.g., drug use) are excluded.
Additional exclusion criteria are current medical conditions that may explain the symptoms (diabetes, heart disease, among others) or significant current (in the past six months) unstable (requiring significant medication adjustments or hospitalization) psychiatric conditions, including suicidal or homicidal ideation, schizophrenia or bipolar disorder according to subject responses to the interview and review by the principal investigator.
Subjects who usually consume abnormally high contents of dietary polyphenol based on a self-reported diet diary will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA- New Jersey Health Care System	East Orange	New Jersey	United States	07018

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai
United States Department of Defense
Department of Veterans Affairs, New Jersey

Investigators

Principal Investigator: Giulio Maria Pasinetti, MD, PhD, Icahn School of Medicine at Mount Sinai
Study Director: Brett Chaney, MD, United States Department of Defense