Glutamate Neuro-Excitotoxicity in GWI

NCT03342482 | Completed DMC

• 1 other identifier: IRB-2017-301
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the proposed research is to examine whether dietary exposure to food additives containing glutamate may be contributing to symptoms in Gulf War Illness (GWI). The rationale for proposed study comes from data in the fibromyalgia field which suggests that reducing the consumption of dietary glutamate can reduce over-excitation in the nervous system, leading to symptom improvement. In prior research, a low-glutamate diet (restricting food additive consumption) was tested in fibromyalgia patients. After one-month on the diet, 84% of patients had \>30% of their symptoms go away (with 11 symptoms remitting on average), and 8 subjects had complete remission of all symptoms. Subjects then had a significant return of symptoms upon challenge with monosodium glutamate (MSG) as compared to placebo. Since there is almost complete symptom overlap between fibromyalgia and GWI, it is of utmost importance to test this diet as a low-cost treatment option in GWI patients. The findings from this research will ultimately be applicable to all GWI patients and potentially to other veterans with a similar symptom profile as well. The ultimate impact of this research could be quite profound, as it has the potential to impact all of the symptoms of GWI, as opposed to being a proposed treatment for only one of the symptoms. This dietary treatment has been shown to dramatically affect symptoms like fatigue, cognitive dysfunction, and pain; and thus, has the potential to dramatically improve quality of life for these individuals. Potential benefits of the treatment are great, and risks are minimal, as the treatment involves shifting the diet to a healthier, whole-food approach. First, the study will confirm or negate the idea that abnormal glutamate signaling in the nervous system could be causing symptoms in GWI. Second, if found to be successful, then this will provide a low-cost, easy-to-implement treatment option for the many veterans suffering from this multi-symptom illness. Third, this research could lead to future studies to identify potential causes of this abnormal neurotransmission, to help prevent future illness onset.

Conditions

Gulf War Syndrome

Keywords

MSG; Gulf War Syndrome; Diet; Glutamate

Outcome Measures

Primary Outcomes (1)

• Symptom Score Change

  The number and type of symptoms will be assessed with a symptom score measure

  Baseline, 1 month, 5th week, 6th week

Secondary Outcomes (1)

• Cognitive Function

  Baseline, 1 month, 5th week, 6th week

Other Outcomes (2)

• Change in EEG

  Baseline, 1 month, 5th week, 6th week

• Change in Brain Glutamate Levels

  Baseline, 1-month

Study Arms (2)

Placebo

PLACEBO COMPARATOR

5 g of placebo (sugar and salt) will be administered in veggie capsules

Other: Low-glutamate diet

MSG

EXPERIMENTAL

5 grams of MSG will be administered in veggie capsules

Other: Low-glutamate diet

Interventions

Low-glutamate diet OTHER

The dietary intervention consists of a one-month low-glutamate diet, followed by a randomized crossover challenge with MSG and placebo to measure return of symptoms.

MSG; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males \& Females
• Served (and was deployed) in the Persian Gulf War
• Fulfill both Kansas and CDC definitions of GWI
• Stable medication regimen for 3 or more months

You may not qualify if:

• Active Duty Military
• Current substance use disorder
• Unwilling to change diet for 2 months
• Severe asthma requiring past hospitalization
• Seizure disorder

Sponsors & Collaborators

• American University: lead
• Georgetown University: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

American University

Washington D.C., District of Columbia, 20016, United States

Location

MeSH Terms

Conditions

Persian Gulf Syndrome

Condition Hierarchy (Ancestors)

Occupational Diseases; War-Related Injuries; Wounds and Injuries

Study Officials

• Kathleen F Holton, PhD

  American University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Subjects will be randomized to immediately start a one-month dietary intervention restricting consumption of glutamate, or will be waitlisted as a control group for the first month, and then will begin the one-month dietary intervention period (which will be completed at home). Then subjects will return to DC, will complete all measures again, and then will participate in a double-blind, placebo-controlled, crossover challenge with MSG and placebo.

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 17, 2017
• Study Start: November 14, 2017
• Primary Completion: July 7, 2020
• Study Completion: August 31, 2020
• Last Updated: January 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)