Mechanisms of Gulf War Illness

NCT05972291 | Recruiting DMC

• 2 other identifiers: SPLD-006-22FI01CX001477
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Many veterans with Gulf War Illness developed chronic gastrointestinal symptoms during their deployment to the Persian Gulf. The pathophysiologic mechanisms of these chronic gastrointestinal symptoms are not well understood but cause significant morbidity in veterans. Our proposed studies will provide an innovative and novel treatment trial for chronic gastrointestinal symptoms in veterans with Gulf War Illness that were deployed into war zones. Given that there are currently no specific treatments for these disorders, and that current symptomatic approaches are far from ideal, proof of principle of our trial would be an extremely important advance as it would not only have a beneficial impact on the health of many thousands of our veterans, but also it would substantially reduce the many negative economic effects of this ailment on the VA Health Care System.

Conditions

Gulf War Illness; Irritable Bowel Syndrome; Gastrointestinal Symptoms

Keywords

gastrointestinal; irritable bowel syndrome; glutamine

Outcome Measures

Primary Outcomes (2)

• To determine if oral glutamine supplementation will improve the Symptom Severity Scale in Veterans with GWI and chronic GI Symptoms.

  It's anticipated that veterans with GWI and GI symptoms will show a significant reduction, compared to placebo, in their chronic GI symptoms as reflected by their Symptom Severity Scale Score following glutamine therapy. For each participating subject, the Symptom Severity Scale score will be measured at baseline, and at 4, 8, and 12 weeks after the start of treatment. The investigators will have Symptom Severity Scale scores at 5 time points in each group (glutamine, placebo). These will be explored graphically with time course plots. At each time point, for Symptom Severity Scale scores, the investigators will also calculate descriptive statistics including mean and standard deviation, as well as median, median absolute deviation and inter-quartile range if the distribution of data is skewed. Box plots will be used to graphically demonstrate the distribution of Symptom Severity Scale scores at each time point. This will be done for both the glutamine and the placebo groups.

  3 years

• To determine if oral glutamine supplementation will restore intestinal permeability in Veterans with GWI.

  Following our recent findings, we expect \>75% of veterans will restore normal intestinal permeability, while in the placebo group, this percentage is \~6%. One sample one sided proportion test (PROC FREQ in SAS) will be used to test whether the proportion of restoration is \>75% in each treatment group (glutamine supplementation or placebo) and two sample one sided proportion tests (PROC FREQ in SAS) to compare the difference between the two groups. To examine the association between the Symptom Severity Scale Score and restoration of normal intestinal permeability, Pearson's correlations between the Symptom Severity Scale and intestinal permeability will be calculated at baseline, and at 4, 8, and 12 weeks after the start of treatment, for both oral glutamine and placebo groups.

  3 years

Study Arms (2)

Oral Glutamine

EXPERIMENTAL

You will be asked to consume 5 grams of glutamine three times a day for 12 weeks. At week four, you will be asked to return to the CRC to be assessed, and then to return every four weeks until week 12, which will be the conclusion of the study.

Dietary Supplement: Oral Glutamine

Whey Protein Powder

PLACEBO COMPARATOR

You will be asked to consume 5 grams of whey protein powder three times a day for 12 weeks. At week four, you will be asked to return to the CRC to be assessed, and then to return every four weeks until week 12, which will be the conclusion of the study.

Other: Control Arm

Interventions

Oral Glutamine DIETARY_SUPPLEMENT

You will receive an unmarked packet with either glutamine or whey protein powder. Once the packet is opened, the powder should be mixed completely with 8 oz of water. You should completely drink this mixture within 10 minutes. You will consume one packet three times a day for 12 weeks. One packet 30 minutes before breakfast, one packet 30 minutes before lunch, and one packet 30 minutes before the evening meal.

Oral Glutamine

Control Arm OTHER

You will receive an unmarked packet with either glutamine or whey protein powder. Once the packet is opened, the powder should be mixed completely with 8 oz of water. You should completely drink this mixture within 10 minutes. You will consume one packet three times a day for 12 weeks. One packet 30 minutes before breakfast, one packet 30 minutes before lunch, and one packet 30 minutes before the evening meal.

Whey Protein Powder

Eligibility Criteria

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

You may qualify if:

• Veterans 18-65 years old with GWI and chronic GI symptoms (abdominal pain, diarrhea, bloating) that started during their deployment in the Persian Gulf
• Veterans 18-65 years old with GWI and chronic GI symptoms (abdominal pain, diarrhea, bloating)
• increased intestinal permeability on the lactulose/mannitol permeability test (ratio \>0.07)
• able and willing to cooperate with the study

You may not qualify if:

• current participation in another research protocol or unable to give informed consent
• women with a positive urine pregnancy test or breastfeeding
• history of inflammatory bowel disease, lactose intolerance and/or celiac sprue
• \+ hydrogen breath test for bacterial overgrowth
• \+ anti-endomysial antibody titer
• use of NSAIDs 2 weeks before or during the study
• known allergy to glutamine or whey protein
• abdominal surgery except for removal of gallbladder, uterus, or appendix \>6 months prior to entry into the study
• Abnormal serum BUN and/or creatinine
• Mannitol recovery out of the normal range of 5-25 U/g
• history of kidney disease
• allergies to monosodium glutamate
• current use of anti-seizure medications

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Memphis VA Medical Center, Memphis, TN

Memphis, Tennessee, 38104-2127, United States

RECRUITING

MeSH Terms

Conditions

Irritable Bowel Syndrome

Interventions

Glutamine

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Study Officials

• QiQi Zhou, MD PhD

  Memphis VA Medical Center, Memphis, TN

  PRINCIPAL INVESTIGATOR

• George N Verne

  Memphis VA Medical Center, Memphis, TN

  PRINCIPAL INVESTIGATOR

Central Study Contacts

George N Verne

CONTACT

(901) 523-8990; George.Verne@va.gov

QiQi Zhou, MD PhD

CONTACT

(901) 523-8990; qiqi.zhou@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Each person in this study will receive either glutamine or whey powder to mix in with water. This is done by a random assignment using a computer program for "yes" or "no". All odd numbers of participants will undergo the random choice of the computer program. All even number participants will get the opposite treatment of the previous odd number participant.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: In this study, the investigators will conduct a randomized, double-blind, placebo-controlled clinical trial studying glutamine 5 grams orally three times a day compared to a placebo 5 grams orally three times a day for 12 weeks in 80 Veterans with GWI and GI symptoms. This study will also look at Veterans that have chronic GI symptoms and do not have GWI. The Symptom Severity Scale and intestinal permeability will be measured at baseline, 4, 8, and 12 weeks.

Study Record Dates

• First Submitted: July 24, 2023
• First Posted: August 2, 2023
• Study Start: October 16, 2023
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)