Effects of Botanical Microglia Modulators in Gulf War Illness

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02909686

Enrollment

Registered

2016-09-21

Start date

2016-07-31

Completion date

2022-09-30

Last updated

2025-01-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gulf War Illness

Keywords

Gulf War Syndrome, Chronic Multisymptom Illnesses, Medically Unexplained Illnesses

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.

Interventions

DIETARY_SUPPLEMENTNettle

DIETARY_SUPPLEMENTPycnogenol

DIETARY_SUPPLEMENTReishi Mushroom

DIETARY_SUPPLEMENTResveratrol

DIETARY_SUPPLEMENTPlacebo

DIETARY_SUPPLEMENTBoswellia Serrata

DIETARY_SUPPLEMENTCurcumin

DIETARY_SUPPLEMENTEpimedium

DIETARY_SUPPLEMENTFisetin

DIETARY_SUPPLEMENTLuteolin

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

OTHER

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

MALE

Age

39 Years to 65 Years

Healthy volunteers

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

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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 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 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 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).
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).

Countries

United States

Participant flow

Recruitment details

All participants took as least one botanical. Some then went on to take a second or even third botanical, but not all participants did this. The order was randomized, so not all participants took the same sequence of botanicals.

Pre-assignment details

Participants also took a placebo for each botanical. The order is as follows for each botanical: 30 +/- 3 days pf baseline symptom reports, followed by 30+/- days of placebo, followed by 30+/- days days of lower-dose botanical, followed by 30+/- days of higher-dose botanical.

Participants by arm

Arm	Count
All Participants Participants enrolled in this study were assigned to receive placebo and up to three botanical agents in a psuedo-randomized order. For each botanical condition, participants first received a placebo, followed by a lower dose of botanical and a higher dose of botanical, for up to three different botanicals. After completing the full protocol of three botanicals, participants were then offered the opportunity to re-enroll to receive up to three additional botanicals	36
Total	36

Arm

Count

All Participants

Participants enrolled in this study were assigned to receive placebo and up to three botanical agents in a psuedo-randomized order. For each botanical condition, participants first received a placebo, followed by a lower dose of botanical and a higher dose of botanical, for up to three different botanicals. After completing the full protocol of three botanicals, participants were then offered the opportunity to re-enroll to receive up to three additional botanicals

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Physician Decision	3
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	All Participants
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	5 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) White	30 Participants
Region of Enrollment United States	36 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	36 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk
deaths Total, all-cause mortality	0 / 10	0 / 10	0 / 11	0 / 11	0 / 11	0 / 12	0 / 11	0 / 10	0 / 10	0 / 96
other Total, other adverse events	0 / 10	0 / 10	0 / 11	0 / 11	0 / 11	1 / 12	0 / 11	0 / 10	0 / 10	0 / 96
serious Total, serious adverse events	0 / 10	0 / 10	0 / 11	0 / 11	0 / 11	0 / 12	0 / 11	0 / 10	0 / 10	0 / 96

Outcome results

Primary

Change From Baseline in Overall Gulf War Illness Disease Severity

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).

Time frame: Week 17