Oral Glutamine for Gulf War Syndrome

Overseen By QiQi Zhou, MD PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Must not be taking: NSAIDs, Anti-seizure

Disqualifiers: Inflammatory bowel disease, Lactose intolerance, Celiac sprue, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop using NSAIDs (non-steroidal anti-inflammatory drugs) two weeks before and during the study, and you cannot participate if you are currently using anti-seizure medications.

What data supports the effectiveness of the treatment Oral Glutamine for Gulf War Syndrome?

The BCG vaccine, part of the treatment, has shown potential benefits in other conditions by enhancing the immune system, such as improving lung function in asthma and reducing the severity of cutaneous leishmaniasis in mice. ^{1 2 3 4 5}

How does the BCG vaccine treatment differ for Gulf War Syndrome?

The BCG vaccine, typically used to prevent tuberculosis, is unique in this trial for Gulf War Syndrome due to its potential to modify immune responses, which is not a standard treatment for this condition. ^{1 6 7 8 9}

Research Team

QiQi Zhou, MD PhD

Principal Investigator

Memphis VA Medical Center, Memphis, TN

George N Verne

Principal Investigator

Memphis VA Medical Center, Memphis, TN

Eligibility Criteria

This trial is for veterans aged 18-65 with Gulf War Illness (GWI) and chronic GI symptoms like abdominal pain, diarrhea, or bloating that began during deployment in the Persian Gulf. Participants must show increased intestinal permeability and abstain from alcohol before and during the study. Pregnant women, those with certain medical conditions or allergies, or on specific medications cannot join.

Inclusion Criteria

Increased intestinal permeability on the lactulose/mannitol permeability test (ratio >0.07)

Able and willing to cooperate with the study

I am a veteran aged 18-65 with chronic GI symptoms from my time in the Persian Gulf.

Exclusion Criteria

I am not pregnant or breastfeeding.

Known allergy to glutamine or whey protein

Current participation in another research protocol or unable to give informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either oral glutamine or placebo for 12 weeks, with assessments at weeks 4, 8, and 12

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Control Arm
• Oral Glutamine

Trial Overview The trial is testing Oral Glutamine against a control arm to treat chronic gastrointestinal symptoms in veterans with GWI. The goal is to find an effective treatment where none currently exists, potentially improving veteran health and reducing economic strain on healthcare systems.

Participant Groups

Group I: Oral Glutamine Experimental Treatment 1 Intervention

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.

Group II: Whey Protein Powder Placebo Group 1 Intervention

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.

Control Arm is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as TICE BCG for:

• Bladder cancer

Approved in United States as TheraCys BCG for:

• Bladder cancer

Approved in European Union as OncoTICE for:

• Bladder cancer

Approved in Canada as ImmuCyst for:

• Bladder cancer

Approved in Japan as BCG Vaccine for:

• Bladder cancer
• Tuberculosis

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study involving 4262 newborns, BCG vaccination showed no severe unexpected adverse reactions, indicating a good safety profile for the vaccine.

However, there was a higher incidence of suppurative lymphadenitis (10 cases) than expected, but all cases were treated successfully without long-term complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial. Nissen, TN., Birk, NM., Kjærgaard, J., et al.[2017]

The Bacille Calmette-Guerin (BCG) vaccine is the only available vaccine for tuberculosis (TB) and has shown variable efficacy, with a long-term study indicating a protective efficacy of 52% among American Indians, highlighting its limitations in different populations.

Due to the waning immunity of BCG, there is a significant push for new TB vaccines, with over 200 candidates currently in development, including live attenuated vaccines and recombinant BCG, which are now entering clinical trials to improve protection against TB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent developments in tuberculosis vaccines. Haile, M., Källenius, G.[2019]

In a large study of over 400,000 individuals, the BCG vaccine was not found to reduce the risk of developing relapsing-remitting multiple sclerosis (RRMS), with hazard ratios indicating no significant association during two follow-up periods.

However, there was a positive association between BCG vaccination and other forms of multiple sclerosis, suggesting that the relationship between BCG and MS may depend on the specific phenotype of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada. Corsenac, P., Parent, MÉ., Wolfson, C., et al.[2022]

In a study with 20 participants (9 receiving repeated BCG vaccinations and 11 previously receiving a placebo), repeated BCG vaccination showed a tendency to improve lung function in asthma patients compared to a single vaccination.

The Repeated BCG group exhibited a significant increase in the interferon gamma/interleukin 4 ratio, indicating enhanced Th1 immune response, which suggests that repeated BCG vaccinations could be a promising therapy for asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of BCG revaccination on asthma. Choi, IS., Koh, YI.[2019]

In a study involving BALB/c mice infected with Leishmania tropica, pretreatment with live Bacillus Calmette-Guerin (BCG) significantly reduced the severity of cutaneous leishmaniasis and decreased mortality rates (p < 0.005).

Mice treated with BCG showed less local inflammation and regional lymphadenopathy, and there was no evidence of the disease spreading to internal organs, indicating a protective effect of BCG against severe disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of BCG on experimental cutaneous leishmaniasis in mice. Weintraub, J., Weinbaum, FI.[2003]

Disseminated BCG disease, a rare but serious complication of the BCG vaccine, primarily affects immunocompromised individuals, particularly infants and those with late-stage AIDS, with a high mortality rate of 71%.

Recent observations indicate that disseminated BCG disease is now occurring in older children and adults, especially those who are HIV-positive, and can also arise after revaccination in individuals who did not respond to the initial vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disseminated bacille Calmette-Guérin disease after vaccination: case report and review. Talbot, EA., Perkins, MD., Silva, SF., et al.[2022]

BCG revaccination significantly increased the immune response in infants, particularly enhancing the production of the cytokine IFN-γ, which is important for fighting infections, with the strongest effects observed shortly after vaccination.

The immunological effects of BCG varied based on factors like sex, prior DTP-booster vaccination, and micronutrient supplementation, suggesting that these factors may influence the overall effectiveness of BCG in improving survival rates in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age. Andersen, A., Roth, A., Jensen, KJ., et al.[2021]

BCG (Bacille Calmette-Guerin) is a well-established adjuvant for vaccines against leprosy and tuberculosis, highlighting its effectiveness in enhancing immune responses.

Recent discussions suggest that BCG may also play a role in controlling parasite infections like leishmaniasis, paving the way for the development of recombinant BCG vaccines specifically targeting parasites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCG: a modifier of immune responses to parasites. Frommel, D., Lagrange, PH.[2019]

In a study of 37 patients with high-risk bladder cancer, 75.7% remained free of disease recurrence after receiving 6 weekly BCG treatments followed by monthly maintenance for one year, indicating strong efficacy of this treatment protocol.

The monthly maintenance approach resulted in only 2.7% of patients experiencing severe toxicity (grade 3/4), which is significantly lower than the 26% toxicity rate reported in a previous study (SWOG 8507) with a different maintenance regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guerin. Is monthly maintenance an option for transitional cell carcinoma of the bladder? Flanigan, RC., DeLaurentis, DA., Waters, WB., et al.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Recent developments in tuberculosis vaccines. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guerin vaccination and multiple sclerosis: A population-based birth cohort study in Quebec, Canada. [2022]

4. Denmark pubmed.ncbi.nlm.nih.gov

Effects of BCG revaccination on asthma. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of BCG on experimental cutaneous leishmaniasis in mice. [2003]

6. United States pubmed.ncbi.nlm.nih.gov

Disseminated bacille Calmette-Guérin disease after vaccination: case report and review. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age. [2021]

8. England pubmed.ncbi.nlm.nih.gov

BCG: a modifier of immune responses to parasites. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Bacillus Calmette-Guerin. Is monthly maintenance an option for transitional cell carcinoma of the bladder? [2019]