Trial Outcomes & Findings for Effects of Botanical Microglia Modulators in Gulf War Illness (NCT NCT02909686)

NCT ID: NCT02909686

Last Updated: 2025-01-24

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 36 participants
• Primary outcome timeframe: Week 17
• Results posted on: 2025-01-24

Participant Flow

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.

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.

Participant milestones

Measure	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. Dietary Supplement: Boswellia Serrata 400-800mg in capsule form by mouth every day Dietary Supplement: Curcumin 1000-2000mg in capsule form by mouth every day Dietary Supplement: Epimedium 1000-2000mg in capsule form by mouth every day Dietary Supplement: Fisetin 200-800mg in capsule form by mouth every day Dietary Supplement: Luteolin 200-400mg in capsule form by mouth every day Dietary Supplement: Nettle 435-1305mg in capsule form by mouth every day Dietary Supplement: Pycnogenol 200-400mg in capsule form by mouth every day Dietary Supplement: Reishi 1600-3200mg in capsule form by mouth every day Dietary Supplement: Resveratrol 200-600mg in capsule form by mouth every day Dietary Supplement: Placebo in capsule form by mouth every day
Overall Study STARTED	96
Overall Study Boswellia Serrata	10
Overall Study Curcumin	10
Overall Study Epimedium	11
Overall Study Fisetin	11
Overall Study Luteolin	11
Overall Study Nettle	12
Overall Study Pycnogenol	11
Overall Study Reishi Mushroom	10
Overall Study Resveratrol	10
Overall Study Placebo	96
Overall Study COMPLETED	91
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Measure	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. Dietary Supplement: Boswellia Serrata 400-800mg in capsule form by mouth every day Dietary Supplement: Curcumin 1000-2000mg in capsule form by mouth every day Dietary Supplement: Epimedium 1000-2000mg in capsule form by mouth every day Dietary Supplement: Fisetin 200-800mg in capsule form by mouth every day Dietary Supplement: Luteolin 200-400mg in capsule form by mouth every day Dietary Supplement: Nettle 435-1305mg in capsule form by mouth every day Dietary Supplement: Pycnogenol 200-400mg in capsule form by mouth every day Dietary Supplement: Reishi 1600-3200mg in capsule form by mouth every day Dietary Supplement: Resveratrol 200-600mg in capsule form by mouth every day Dietary Supplement: Placebo in capsule form by mouth every day
Overall Study Physician Decision	3
Overall Study Withdrawal by Subject	2

Baseline Characteristics

Effects of Botanical Microglia Modulators in Gulf War Illness

Baseline characteristics by cohort

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

PRIMARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Overall Gulf War Illness Disease Severity	13 units on a scale Standard Error .43	0 units on a scale Standard Error .32	8 units on a scale Standard Error 1.56	-1 units on a scale Standard Error 2.08	12 units on a scale Standard Error .90	19 units on a scale Standard Error 1.08	15 units on a scale Standard Error 1.18	-5 units on a scale Standard Error 2.08	14 units on a scale Standard Error 1.1	7 units on a scale Standard Error 1.37

SECONDARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Pain Severity	13 units on a scale Standard Error 1.12	-1 units on a scale Standard Error .95	8 units on a scale Standard Error 1.15	1 units on a scale Standard Error 1.87	11 units on a scale Standard Error .94	14 units on a scale Standard Error 1.35	13 units on a scale Standard Error 1.07	-2 units on a scale Standard Error 1.53	13 units on a scale Standard Error 1.42	6 units on a scale Standard Error 1.31

SECONDARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Fatigue Severity	6 units on a scale Standard Error 2.01	4 units on a scale Standard Error 1.89	4 units on a scale Standard Error 1.89	-5 units on a scale Standard Error 1.99	11 units on a scale Standard Error 1.81	4 units on a scale Standard Error 2.60	3 units on a scale Standard Error 2.03	3 units on a scale Standard Error 0.67	10 units on a scale Standard Error 1.62	4 units on a scale Standard Error 1.46

SECONDARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Cognitive Symptom Severity	-6 units on a scale Standard Error 2.2	7 units on a scale Standard Error 0.70	0 units on a scale Standard Error 1.94	3 units on a scale Standard Error 2.25	-4 units on a scale Standard Error 1.76	-11 units on a scale Standard Error 1.34	-8 units on a scale Standard Error 1.71	-1 units on a scale Standard Error 2.33	-9 units on a scale Standard Error 1.61	-4 units on a scale Standard Error 1.57

SECONDARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Mood Symptom Severity	7 units on a scale Standard Error 1.84	12 units on a scale Standard Error 1.1	6 units on a scale Standard Error 1.94	0 units on a scale Standard Error 1.42	1 units on a scale Standard Error 1.74	-9 units on a scale Standard Error 0.99	-7 units on a scale Standard Error 1.26	0 units on a scale Standard Error 0.02	-3 units on a scale Standard Error 1.63	1 units on a scale Standard Error 1.53

SECONDARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Dermatological Symptom Severity	3 units on a scale Standard Error 0.38	-4 units on a scale Standard Error 0.29	-3 units on a scale Standard Error 0.29	0 units on a scale Standard Error 0.75	1 units on a scale Standard Error 0.55	1 units on a scale Standard Error 0.48	3 units on a scale Standard Error 0.42	-2 units on a scale Standard Error 1.14	2 units on a scale Standard Error 0.51	0 units on a scale Standard Error 0.57

SECONDARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Respiratory Symptom Severity	-3 units on a scale Standard Error 0.91	-1 units on a scale Standard Error 1.07	-5 units on a scale Standard Error 0.42	0 units on a scale Standard Error 1.15	3 units on a scale Standard Error 0.59	-2 units on a scale Standard Error 0.50	-1 units on a scale Standard Error 0.66	0 units on a scale Standard Error 1.08	1 units on a scale Standard Error 0.67	0 units on a scale Standard Error 0.66

SECONDARY outcome

Timeframe: Week 17

Population: Participants assigned to multiple arms

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).

Outcome measures

Measure	Boswellia Serrata n=10 Participants 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 Participants 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=10 Participants 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=10 Participants 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=10 Participants 200-400mg in capsule form by mouth every day Luteolin	Nettle n=10 Participants 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=10 Participants 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 Participants 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=9 Participants 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=89 Participants in capsule form by mouth every day Placebo
Change From Baseline in Gastrointestinal Symptom Severity	9 units on a scale Standard Error 0.39	-5 units on a scale Standard Error 2.04	-2 units on a scale Standard Error 1.37	8 units on a scale Standard Error 0.85	6 units on a scale Standard Error 0.66	1 units on a scale Standard Error 1.07	4 units on a scale Standard Error 0.84	-12 units on a scale Standard Error 1.20	1 units on a scale Standard Error 1.48	1 units on a scale Standard Error 1.18

Adverse Events

Boswellia Serrata

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Curcumin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Epimedium

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Fisetin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Luteolin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Nettle

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Pycnogenol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Reishi Mushroom

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Resveratrol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Boswellia Serrata n=10 participants at risk 400-800mg in capsule form by mouth every day Boswellia Serrata	Curcumin n=10 participants at risk 1000-2000mg in capsule form by mouth every day Curcumin	Epimedium n=11 participants at risk 1000-2000mg in capsule form by mouth every day Epimedium	Fisetin n=11 participants at risk 200-800mg in capsule form by mouth every day Fisetin	Luteolin n=11 participants at risk 200-400mg in capsule form by mouth every day Luteolin	Nettle n=12 participants at risk 435-1305mg in capsule form by mouth every day Nettle	Pycnogenol n=11 participants at risk 200-400mg in capsule form by mouth every day Pycnogenol	Reishi Mushroom n=10 participants at risk 1600-3200mg in capsule form by mouth every day Reishi Mushroom	Resveratrol n=10 participants at risk 200-600mg in capsule form by mouth every day Resveratrol	Placebo n=96 participants at risk in capsule form by mouth every day Placebo
Hepatobiliary disorders Elevated Liver Enzyme	0.00% 0/10 • 10 months	0.00% 0/10 • 10 months	0.00% 0/11 • 10 months	0.00% 0/11 • 10 months	0.00% 0/11 • 10 months	8.3% 1/12 • Number of events 1 • 10 months	0.00% 0/11 • 10 months	0.00% 0/10 • 10 months	0.00% 0/10 • 10 months	0.00% 0/96 • 10 months

Additional Information

Dr. Jarred Younger

University of Alabama at Birmingham

Phone: 205-975-5821

Email: youngerlab@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place