Confirmation of Diet as a Treatment for Gulf War Illness

This clinical trial aims to confirm previous findings from a smaller study which demonstrated significant improvements in all symptoms among veterans with Gulf War Illness after one month on the dietary intervention. The main objectives of this study are: 1) to confirm previous findings of treatment response to the diet in a larger and more diverse group; 2) to examine how changes in the nervous system may be the reason for improvement; and 3) to identify markers which change in the blood after one month on the diet. Participants will have baseline measures collected and then will be randomized into the intervention or wait-listed control group, which they will follow for one month before being reassessed.

Study Overview

• Status: Recruiting
• Conditions: Gulf War Syndrome; Gulf War Illness
• Intervention / Treatment: Behavioral: Dietary Intervention

Detailed Description

The rationale for the proposed research comes from observations from a smaller study which demonstrated profound widespread symptom improvements in veterans with Gulf War Illness (GWI) after one month on the diet. Improvements were noted in every symptom domain and included significant reductions in overall symptom number (with an average of 9 symptoms going away), reduced pain, fatigue, depression, anxiety, and post-traumatic stress disorder (PTSD); and concurrent significant improvements in cognitive function and quality of life. Results also demonstrated that those who improved on the diet had a significant reduction in peripheral inflammation, as compared to those who did not improve on the diet. These benefits have been observed without any negative side effects and the majority of participants continued to follow the diet three months after study completion, suggesting continued improvement and good feasibility. The objectives of this study are: 1) to evaluate whether or not the substantial benefits observed in the recently completed clinical trial hold in a larger group of more diverse veterans with GWI, and 2) to identify blood and/or brain measures which predict improvement on the diet. By recruiting a large group of veterans which are representative of those with GWI, the findings of this research should be applicable to the larger GWI community. The impact of this research could be quite profound, with the diet being a no-risk, low-cost treatment option with no side effects, which allows each individual veteran to take back control of his/her health. There are no direct risks to following the diet since it is a healthy whole-food dietary approach which provides all necessary nutrients. The potential benefits of the diet include improvement in GWI symptoms; improvement in quality of life, potential for improvement in other health markers related to diet (such as obesity, diabetes, cardiovascular disease, high blood pressure) and the possibility of benefit to the larger community. If positive results are confirmed in the proposed study, then the next step would be to teach all Veterans Administration (VA) dietitians how to administer the low glutamate diet so that all veterans have access to it, which should be possible within 1-2 years of the completion of this study.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Houra Taheri, PhD; Phone Number: 202- 885-3810; Email: htaheri@american.edu
• Study Contact Backup: Name: Kathleen F Holton, PhD, MPH; Phone Number: 202-885-3797; Email: holton@american.edu

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Recruiting
      • American University
      • Contact: Houra Taheri, PhD; Email: htaheri@american.edu
      • Principal Investigator: Kathleen F Holton, PhD, MPH
  • Florida
    • Fort Lauderdale, Florida, United States, 33314
      • Recruiting
      • Nova Southeastern University
      • Principal Investigator: Amanpreet Cheema, PhD
      • Contact: Oleksandra Shchebet; Phone Number: 954-262-2896; Email: oshchebe@nova.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Recruiting
      • Boston University
      • Principal Investigator: Kimberly Sullivan, PhD
      • Contact: Dylan Keating; Phone Number: 617-358-2230; Email: dmk13@bu.edu
      • Contact: Camryn Isemann; Phone Number: 617-358-1717; Email: camryns@bu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and Females of all races and ethnicities who are ≤75 yrs of age
• Served in the 1990-1991 Persian Gulf War
• Fulfill both Center for Disease Control (CDC) and Kansas definitions of Gulf War Illness
• Stable medication regimen for ≥1 month and willing to keep medications and supplements stable throughout study participation

Exclusion Criteria:

• Recent substance use disorder (past year)
• Unwilling to stop using alcohol, tobacco (including vaping) and/or marijuana; or unwilling to change diet
• Diagnosed seizure disorder or severe asthma requiring past hospitalization
• Currently taking medication which affects glutamatergic or GABAergic neurotransmission (but can work with their physician to wean off of these medications prior to participating)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dietary Intervention Group; Subjects will undergo a 2-hour in-depth training via Zoom on how to follow the diet and will receive a binder with helpful information. They will be give the weekend to prepare and then will start the diet the following Monday, and will continue following it for 4 weeks before being reassessed in the lab.	Behavioral: Dietary Intervention; This is a whole food, nutrient-dense diet that aims to remove exposure to specific food additives thought to have negative neurological effects, while also optimizing micronutrient intake.
No Intervention: Waitlisted Control Group; The waitlisted control group will follow their usual diet for one month and then will be reassessed (as a comparator group) before being trained on the dietary intervention which they will then follow for the next month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Symptom Score	This measure computes the number of symptoms being experienced in this widespread chronic pain condition, and also computes a score based on severity of each symptom. The raw symptom score ranges from 0-32, and the symptom severity score ranges from 0-96, with higher scores indicative of worse outcomes.	1-month
Patient Global Impression of Change Scale (PGIC)	The PGIC is a self-report measure of the amount of change experienced from the treatment using a 7-point scale with the following options: very much worse, much worse, a little worse, no change, a little better, much better, very much better.	1-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
McGill Pain Questionnaire	This pain measure inquires about types of pain sensation ranked on a scale of 0 to 3, with a total score from 0-45. Higher scores indicate worse pain.	1-month
Chalder Fatigue Score	The Chalder Fatigue Scale measures the extent and severity of fatigue. It is a scale with answers to each question based on both bimodal and likert scores, resulting in a total score of 0-11 and 0-33, with higher scores indicating more fatigue.	1-month
Veterans RAND 36 Item Health Survey (VR-36)	This is a 36-item survey used to measure health related quality of life, to estimate disease burden and to evaluate disease-specific impact on general and selected populations. The items on the questionnaire correspond to eight principal health domains including general health perceptions, physical functioning, role limitations due to physical and emotional problems, bodily pain, energy-fatigue, social functioning and mental health. This results in physical and mental health component quality of life scores, each scored from 0-100, with higher scores indicating a better quality of life.	1-month
Brief Irritability Questionnaire (BITe)	This short questionnaire assesses anger and irritability with 5 questions ranked on a 6-point scale. Higher scores indicate more irritability.	1-month
Center for Epidemiological Studies Depression Scale (CES-D)	This is a 20-item measure that asks individuals to rate how often over the past week they experienced symptoms associated with depression, such as restless sleep, poor appetite, and feeling lonely. Response options range from 0 to 3 for each item (0 = Rarely or None of the Time, 1 = Some or Little of the Time, 2 = Moderately or Much of the time, 3 = Most or Almost All the Time). Scores range from 0 to 60, with high scores indicating greater depressive symptoms.	1-month
Generalized Anxiety Disorder Scale (GAD-7)	A brief questionnaire with 7 questions which measure generalized anxiety disorder. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Total scores range from 0-21, with higher scores indicating more anxiety.	1-month
PTSD Checklist for DSM-5 (PCL-5)	The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The self-report rating scale is 0-4 for each symptom, reflecting a change from 1-5 in the DSM-IV version. Rating scale descriptors are the same: "Not at all," "A little bit," Moderately," "Quite a bit," and "Extremely." A total symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items, with higher total scores indicating a higher probability of having PTSD.	1-month
Cognitive Testing	Cognitive function will be measured using computerized cognitive testing software and one administered exam in-person. An overall score, called a neurocognitive index, is computed as the average of 5 domain scores, with higher scores equating to better cognitive function.	1-month
Dolorimetry	Pain threshold will be measured using a dolorimeter, where pressure is applied to 18 points on the body that are typically tender in widespread chronic pain conditions. The participant will report when pain starts and the kilograms of pressure will be recorded. These will be averaged over the 18 sites, with higher scores indicative of having a higher (better) pain threshold.	1-month
Biophotonic scanner	A biophotonic scanner will be used to assess long-term carotenoid intake from the diet. This is a painless test where an infared light is shone through the index finger. This results in a numeric score from 0-800, with a higher score indicative of higher dietary carotenoid intake.	1-month

Collaborators and Investigators

• Sponsor: American University
• Collaborators: Boston University; Massachusetts General Hospital; Georgetown University; Nova Southeastern University
• Investigators: Principal Investigator: Kathleen F Holton, PhD, MPH, American University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 9, 2023

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 5, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Treatment; Gulf War Syndrome; Gulf War Illness; Diet; GWI
• Additional Relevant MeSH Terms: Wounds and Injuries; Occupational Diseases; War-Related Injuries; Persian Gulf Syndrome
• Other Study ID Numbers: 2023-46; CDMRP-GW210080 (Other Grant/Funding Number: Department of Defense)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No