Curcumin, Resveratrol, and Stinging Nettle as Treatments for GWI

NCT ID: NCT05377242

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 390 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-31
• Study Completion Date: 2026-06-30

Brief Summary

This project's objective is to identify effective treatments for Gulf War Illness (GWI). The project tests three potential treatments: curcumin, stinging nettle, and resveratrol. The project uses a decentralized clinical trial (DCT) design in which individuals can participate from anywhere in the United States. Recruitment efforts will be designed to obtain a geographically and demographically diverse study sample.

Detailed Description

The project is funded by the Congressionally Directed Medical Research Programs (CDMRP) of the U.S. Department of Defense.

The study uses a prospective, pseudo-randomized, placebo-controlled, blinded, within-person clinical trial design. The trials are conducted decentralized, with all protocols performed remotely. Three-hundred individuals will be recruited in the study.

Recruitment for this study will come from a database of participant who have agreed to be contacted about future studies from our previous studies. Participants will also be recruited through the Gulf War Illness Clinical Trials and Intervention Consortium (GWICTIC) through our collaboration with Nova Southeastern University. The Consortium includes a database of individuals with Gulf War Illness who had agreed to be contacted for research studies. No other information will be shared with Nova Southeastern University unless specified and agreed upon. We will also use social media advertisements in partnership with High Level Marketing to recruit for this trial.

In accordance with the Institute of Medicine (IOM) 2014 guidance, participants must meet both the Kansas and CDC (Centers for Disease Control and Prevention) Case Definitions of GWI. Participants must have been deployed to the Persian Gulf Region during the 1990-1991 Gulf War, meet symptom domain criteria, and not have other exclusionary medical conditions.

All potential participants will fill out a online screening survey to assess eligibility. If they are deemed eligible for consent, participants will undergo a zoom meeting with a member of the study staff to sign the consent form. During that meeting, the study staff will explain the consent form in detail and answer any questions about the study or the consent form. The consenting process will follow the same procedure as typically done in face-to-face consenting, and the consent form will be digitally signed during or within 24 hours after the meeting. After providing informed consent, participants will take a post-consent survey to confirm eligibility before entering the study protocol.

Participants will also be required to obtain safety tests via LabCorp or Quest Diagnostics to assess renal and hepatic function, along with collecting C-Reactive Protein readings. Because kidney and liver function are important in the metabolism and excretion of the botanicals, it must be determined that these systems can tolerate the addition of a new daily treatment. All participants will received a baseline and mid-point test of kidney and liver function. Individuals with abnormal results on these tests will not proceed with the study or receive study botanicals. Participants can obtain the tests either at a local LabCorp or Quest Diagnostics site to have blood drawn for standard hepatic and renal panels. The hepatic panel includes measuring protein, albumin, globulin, albumin/globulin ratio, total bilirubin, indirect bilirubin, alkaline phosphatase, aspartate transaminase, and alanine transaminase. Results from the blood test will be sent to the participant at their request and to the study coordinator to confirm eligibility. The information will be de-identified and only associated with the individualized study identifier.

If eligible, participants will be randomly assigned a botanical in a double-blind fashion. Participants will then begin the baseline phase of 30 days. During that time, they will complete all baseline questionnaires and will also begin the weekly symptom severity reports and primary outcome measures. A research team member will speak with the participant to set up their electronic device connections and will verify the information is received. Participants will complete all weekly measures on a computer, tablet, or phone. Individuals without an appropriate device will be sent one by the research team. The VR-12 and PGIC secondary outcomes will be given once per week during the weekly questionnaire. The 30-day period will serve as the baseline phase for all analyses. During the baseline phase and after checking that there were no exclusionary kidney or liver concerns, participants will be sent capsules. Capsules will be sent via FedEx in blister packs that indicate what order to take the botanicals. The first shipment of capsules will contain two months of capsules. On Day 31, individuals will being taking the assigned capsules in the morning and again in the evening. During this time, they will continue completing weekly symptom reports, and weekly primary and secondary outcome reports. Participants will complete one month of baseline, eight months of capsules, and one month of endline. At Day 300, their participation will be successfully completed, and they will be fully debriefed by a member of the study team soon after completion.

Consented individuals will be randomized in a double-blind fashion to either the curcumin, resveratrol, or stinging nettle treatment. The curcumin, resveratrol, and stinging nettle trials all follow the same design and procedures. Participants will be blinded not only to the botanical they receive, but also to the schedule of receiving placebo and dosage changes. The randomization schedule will be held by Dr. Nancy Klimas and Dr. Amanpreet Cheema from Nova Southeastern University.

Placebo capsules will be created to keep the same appearance to treatment capsules. Both placebo (microcrystalline cellulose) and active treatment capsules will be over-encapsulated with the same gel caps. Participants will take the same number of capsules in the morning and night throughout participation so that individuals cannot determine when active treatment is initiated and when dosage is changed. Capsules for each day are stored in well-marked, daily blister packs that ensure the participants are taking the correct capsules.

Treatment adherence is using weekly surveys. All botanicals used in this study are commercially available, and there are no critical reagents to obtain. The botanicals are provided by Pure Encapsulations and Nature's Way. Weekly symptom reports begin during baseline. Participants are not aware of when they change conditions, as the appearance and number of capsules are kept the same throughout participation. Symptom severity reports are provided at the end of each week for the entire duration of participation, and primary outcome assessments (the Veterans Rand 12-Item Health Survey) are also given once per week.

Conditions

Gulf War Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Gulf War Veterans, Curcumin

All GWI Veterans will undergo the same screening and experimental procedures. Participants must meet both the Kansas and CDC (Centers for Disease Control and Prevention) Case Definitions of GWI. Participants must have been deployed to the Persian Gulf Region during the 1990-1991 Gulf War, meet symptom domain criteria, and not have exclusionary medical conditions. This trial tests three interventions, which are all tested independently. Participants will receive only one of the three interventions. The curcumin, resveratrol, and stinging nettle trials all follow the same design and procedures.

Participants will complete one month of baseline, eight months of capsules, and one month of endline measurements.

Group Type: EXPERIMENTAL

Curcumin

Intervention Type: DIETARY_SUPPLEMENT

Curcumin (chemical C21H20O6) is derived from turmeric (Curcuma longa) root extract, standardized to contain 95% curcuminoids. The greatest obstacle with curcumin is its poor natural bioavailability. To help circumvent that issue, a piperazine is included as black pepper 5.3mg (Piper nigrum) fruit extract standardized to 95% piperine. The botanical we are using is provided by Pure Encapsulations. Curcumin being used in this study is a commercially available dietary supplement and is classified as food by the FDA instead of a drug.

100 participants will be randomized to receive curcumin. Participants will receive placebo, low-dose (500 mg/day), medium-dose (1000 mg/day), and/or high dose (2000 mg/day) curcumin in a randomized order.

Gulf War Veterans, Resveratrol

All GWI Veterans will undergo the same screening and experimental procedures. Participants must meet both the Kansas and CDC (Centers for Disease Control and Prevention) Case Definitions of GWI. Participants must have been deployed to the Persian Gulf Region during the 1990-1991 Gulf War, meet symptom domain criteria, and not have exclusionary medical conditions. This trial tests three interventions, which are all tested independently. Participants will receive only one of the three interventions. The curcumin, resveratrol, and stinging nettle trials all follow the same design and procedures.

Participants will complete one month of baseline, eight months of capsules, and one month of endline measurements.

Group Type: EXPERIMENTAL

Resveratrol

Intervention Type: DIETARY_SUPPLEMENT

Resveratrol (chemical C14H12O3) is provided as 99% Pure Trans-Resveratrol (MegaResveratrol) from polygonum cuspidatum root). Resveratrol being used in this study is a commercially available dietary supplement and is classified as food by the FDA instead of a drug.

100 participants will be randomized to receive resveratrol. Participants will receive placebo, low-dose (250 mg/day), medium-dose (500mg/day), and/or high dose (1000mg/day) resveratrol in a randomized order.

Gulf War Veterans, Stinging Nettle

All GWI Veterans will undergo the same screening and experimental procedures. Participants must meet both the Kansas and CDC (Centers for Disease Control and Prevention) Case Definitions of GWI. Participants must have been deployed to the Persian Gulf Region during the 1990-1991 Gulf War, meet symptom domain criteria, and not have exclusionary medical conditions. This trial tests three interventions, which are all tested independently. Participants will receive only one of the three interventions. The curcumin, resveratrol, and stinging nettle trials all follow the same design and procedures.

Participants will complete one month of baseline, eight months of capsules, and one month of endline measurements.

Group Type: EXPERIMENTAL

Stinging Nettle

Intervention Type: DIETARY_SUPPLEMENT

Stinging nettle is derived from nettle (Urtica spp) leaf. The botanical we are using is provided by Pure Encapsulations. Stinging Nettle being used in this study is a commercially available dietary supplement and is classified as food by the FDA instead of a drug.

100 participants will be randomized to receive stinging nettle. Participants will receive placebo, low-dose (435mg/day), medium-dose (870mg/day), and/or high dose (2610mg/day) stinging nettle in a randomized order.

Interventions

Curcumin

Curcumin (chemical C21H20O6) is derived from turmeric (Curcuma longa) root extract, standardized to contain 95% curcuminoids. The greatest obstacle with curcumin is its poor natural bioavailability. To help circumvent that issue, a piperazine is included as black pepper 5.3mg (Piper nigrum) fruit extract standardized to 95% piperine. The botanical we are using is provided by Pure Encapsulations. Curcumin being used in this study is a commercially available dietary supplement and is classified as food by the FDA instead of a drug.

100 participants will be randomized to receive curcumin. Participants will receive placebo, low-dose (500 mg/day), medium-dose (1000 mg/day), and/or high dose (2000 mg/day) curcumin in a randomized order.

Intervention Type: DIETARY_SUPPLEMENT

Resveratrol

Resveratrol (chemical C14H12O3) is provided as 99% Pure Trans-Resveratrol (MegaResveratrol) from polygonum cuspidatum root). Resveratrol being used in this study is a commercially available dietary supplement and is classified as food by the FDA instead of a drug.

100 participants will be randomized to receive resveratrol. Participants will receive placebo, low-dose (250 mg/day), medium-dose (500mg/day), and/or high dose (1000mg/day) resveratrol in a randomized order.

Intervention Type: DIETARY_SUPPLEMENT

Stinging Nettle

Stinging nettle is derived from nettle (Urtica spp) leaf. The botanical we are using is provided by Pure Encapsulations. Stinging Nettle being used in this study is a commercially available dietary supplement and is classified as food by the FDA instead of a drug.

100 participants will be randomized to receive stinging nettle. Participants will receive placebo, low-dose (435mg/day), medium-dose (870mg/day), and/or high dose (2610mg/day) stinging nettle in a randomized order.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Urtica dioica

Eligibility Criteria

Inclusion Criteria

• Meets Kansas GWI Case Definition
• Meets CDC GWI Case Definition
• Able to commit to a 10-month study

Exclusion Criteria

• Currently involved in an experimental treatment study
• Abnormal liver function values
• Abnormal kidney function values
• Currently pregnant
• Blood clotting disorder (contraindicated with all three botanicals)
• Reported diagnosis of diabetes with an A1C greater than 9
• The use of contraindicated medications (see below):
• Anticoagulant medications (such as warfarin, heparin, etc.)
• Lithium
• Tacrolimus (Prograf)
• Cancer medications (Alkylating agents, antitumor antibiotics, Topoisomerase I inhibitors, Tamoxifen)

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Congressionally Directed Medical Research Programs

FED

Sponsor Role: collaborator

Responsible Party

Jarred Younger

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jarred Younger, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

Donovan EK, Kekes-Szabo S, Lin JC, Massey RL, Cobb JD, Hodgin KS, Ness TJ, Hangee-Bauer C, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Curcumin (Curcuma longa), Boswellia (Boswellia serrata), and French Maritime Pine Bark (Pinus pinaster). Int J Environ Res Public Health. 2021 Mar 3;18(5):2468. doi: 10.3390/ijerph18052468.

Reference Type: BACKGROUND

PMID: 33802272 (View on PubMed)

Hodgin KS, Donovan EK, Kekes-Szabo S, Lin JC, Feick J, Massey RL, Ness TJ, Younger JW. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), Luteolin, and Fisetin (Rhus succedanea). Int J Environ Res Public Health. 2021 Mar 3;18(5):2483. doi: 10.3390/ijerph18052483.

Reference Type: BACKGROUND

PMID: 33802381 (View on PubMed)

Younger J, Donovan EK, Hodgin KS, Ness TJ. A Placebo-Controlled, Pseudo-Randomized, Crossover Trial of Botanical Agents for Gulf War Illness: Reishi Mushroom (Ganoderma lucidum), Stinging Nettle (Urtica dioica), and Epimedium (Epimedium sagittatum). Int J Environ Res Public Health. 2021 Apr 1;18(7):3671. doi: 10.3390/ijerph18073671.

Reference Type: BACKGROUND

PMID: 33915962 (View on PubMed)

Other Identifiers

W81XWH-22-1-0420

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

GW210009

Identifier Type: -

Identifier Source: org_study_id