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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 36

Inclusion Criteria

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

Exclusion Criteria

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

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	Week 17	Self reported Gulf War Illness symptom severity evening reports were collected for the duration of the study. Scale= change from baseline in overall GWI Disease severity (-100 to +100, with positive numbers indicating how much the symptom improved).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Dermatological Symptom Severity	Week 17	Self reported Dermatological Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Dermatological Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Change From Baseline in Pain Severity	Week 17	Self reported pain symptom severity evening reports were collected for the duration of the study. Scale= change from baseline in overall GWI pain severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Change From Baseline in Fatigue Severity	Week 17	Self reported fatigue symptom severity evening reports were collected for the duration of the study. Scale= change from baseline in overall GWI fatigue severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Change From Baseline in Cognitive Symptom Severity	Week 17	Self reported Cognitive Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Cognitive Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Change From Baseline in Respiratory Symptom Severity	Week 17	Self reported Respiratory Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Respiratory Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Change From Baseline in Mood Symptom Severity	Week 17	Self reported Mood Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Mood Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).
Change From Baseline in Gastrointestinal Symptom Severity	Week 17	Self reported Gastrointestinal Symptom Severity evening reports were collected for the duration of the study. Scale= change from baseline in overall Gastrointestinal Symptom Severity (-100 to +100, with positive numbers indicating how much the symptom improved).