Effects of Botanical Microglia Modulators in Gulf War Illness

Not Applicable

Completed

• Conditions: Gulf War Illness
• Interventions: Dietary Supplement: Epimedium; Dietary Supplement: Resveratrol; Dietary Supplement: Luteolin; Dietary Supplement: Reishi Mushroom; Dietary Supplement: Placebo; Dietary Supplement: Fisetin; Dietary Supplement: Pycnogenol; Dietary Supplement: Boswellia Serrata; Dietary Supplement: Curcumin; Dietary Supplement: Nettle

• Registration Number: NCT02909686
• Lead Sponsor: University of Alabama at Birmingham

Brief Summary

The overall objective of this protocol is to test if Gulf War Illness (GWI) involves chronic inflammation that cannot be measured with typical techniques. The investigators will be observing the effects of nine different botanical compounds (supplements) that are known to suppress inflammation. If one of those supplements helps the symptoms of GWI, it will give the investigators information about what is wrong in people with GWI.

Detailed Description

There is still a poor understanding of the pain, fatigue, and other symptoms that affect approximately 250,000 veterans. The precise mechanism of Gulf War Illness (GWI) is not understood, and there is no targeted treatment for the condition. A current model for GWI points to the central nervous system, immune cells, called microglia that may be hyperactive in patients with GWI. Discovering effective treatments for this disorder is a top priority of GWI research.

Given the investigator's preliminary data, it is suspected that GWI is a form of low-level neuroinflammation that involves hypersensitivity of receptors on microglia. In order to help test that hypothesis, the investigators will be administering supplements that have been shown in vitro or animal in vivo to suppress microglia function in a way that is anti-inflammatory and neuroprotective. If any of these agents suppress symptoms in GWI, it will give the investigators important information about the disease that may allow for creation of better diagnostic tools and treatments in future research studies. Observing the effects of the selected nine anti-inflammatory botanical compounds, in this clinical study, is a strong compliment to the ongoing mechanistic GWI research.

Study Timeline

• Study Start: 2016-07
• Study First Submitted: 2016-09-13
• Study First Submitted QC: 2016-09-16
• Study First Posted: 2016-09-21
• Primary Completion: 2019-09
• Study Completion: 2022-09
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-20
• Last Update Posted: 2024-03-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 39

Inclusion Criteria

1. Male
2. Age 39-65, inclusive
3. Veterans who meet the Kansas inclusion criteria for GWI
4. Present in Persian Gulf between 1990 and August 1991
5. Patient completes daily report during 2 week baseline period (at least 80% completion rate)
6. Able to receive a venous blood draw

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Exclusion Criteria

1. Positive rheumatoid factor at screening
2. Positive anti-nuclear antibody at screening
3. C-reactive protein> 3mg/L at screening
4. Erythrocyte Sedimentation Rate> 40mm/hr at screening
5. Auto-immune disorder
6. Diagnosed Rheumatologic Condition
7. Major PTSD symptoms
8. Hypotension (under 90/60 mm Hg) or history of cardiovascular disease
9. Antihypertensive, anticoagulant medication, nitroglycerine, lithium medication use
10. Diabetes with Hemoglobin A1C >9%
11. History of anaphylaxis to study botanical compounds
12. Current daily use of opioid medication
13. Hospital Anxiety and Depression Scale, Depression subscale score of 16 or higher at baseline
14. Current litigation of worker's compensation claim
15. Blood or clotting disorder
16. Acute infection (body temperature over 100 degrees F)
17. Current daily use of confounding-anti-inflammatory medication as part of regular medication regimen
18. Individuals that are not able to read & understand English

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Epimedium	Epimedium	1000-2000mg in capsule form by mouth every day
Resveratrol	Resveratrol	200-600mg in capsule form by mouth every day
Luteolin	Luteolin	200-400mg in capsule form by mouth every day
Reishi Mushroom	Reishi Mushroom	1600-3200mg in capsule form by mouth every day
Placebo	Placebo	in capsule form by mouth every day
Fisetin	Fisetin	200-800mg in capsule form by mouth every day
Pycnogenol	Pycnogenol	200-400mg in capsule form by mouth every day
Boswellia Serrata	Boswellia Serrata	400-800mg in capsule form by mouth every day
Curcumin	Curcumin	1000-2000mg in capsule form by mouth every day
Nettle	Nettle	435-1305mg in capsule form by mouth every day

Primary Outcome Measures

Name	Time	Method
Change from baseline in overall Gulf War Illness disease severity	Average disease severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported Gulf War Illness symptom severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=no symptoms; 100=severe symptoms).

Secondary Outcome Measures

Name	Time	Method
Change from baseline in Dermatological Symptom Severity	Average dermatological symptom severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported dermatological symptom severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=no skin problems at all; 100=severe skin problems).
Change from baseline in Pain Severity	Average pain severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported pain severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=no pain; 100=severe pain).
Change from baseline in Mood Symptom Severity	Average mood severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported mood symptom severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=not good \[mood\] at all; 100=extremely good \[mood\]).
Change from baseline in Gastrointestinal Symptom Severity	Average gastrointestinal symptom severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported gastrointestinal symptom severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=no bowel or GI problems at all; 100=severe bowel or GI problems).
Change from baseline in Respiratory Symptom Severity	Average respiratory symptom severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported respiratory symptom severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=no breathing or respiratory problems at all; 100=severe breathing or respiratory problems).
Change from baseline in Fatigue Severity	Average fatigue severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported fatigue severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=not fatigued at all; 100=severely fatigued).
Change from baseline in Cognitive Symptom Severity	Average cognitive symptom severity during the last two weeks of each treatment, compared to average severity during the last two weeks of placebo, as well as baseline.	Self reported cognitive symptom severity reported twice daily, in the morning and evening, for the duration of the study. Single item scored 0-100 (0=not \[able to think and remember\] clearly at all; 100=\[able to think and remember\] very clearly).

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States