Clinical trial NCT05377242: Curcumin, Resveratrol, and Stinging Nettle as Treatments for GWI
Official title: Curcumin, Resveratrol, and Stinging Nettle as Treatments for Gulf War Illness
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Gulf War Illness
Keywords: Gulf War Illness
Botanicals
Remote
Clinical Trial
Curcumin
Resveratrol
Stinging Nettle
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Congressionally Directed Medical Research Programs
First posted: 2022-05-17
Enrollment: 300
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: The study uses a prospective, pseudo-randomized, placebo-controlled, blinded, within-person clinical trial design. Individuals will be randomized in a double-blind fashion to either the curcumin, resveratrol, or stinging nettle treatment.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusionary medical conditions. The case definitions will be used for inclusionary screening purposes.

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)

Primary outcomes:
measure: Average Veterans Rand 12-Item Health Survey (VR-12) Physical Functioning Score
timeFrame: This outcome will be assessed weekly, for up to 44 weeks.
measure: Average Veterans Rand 12-Item Health Survey (VR-12) Mental Functioning Score
timeFrame: This outcome will be assessed weekly, for up to 44 weeks.
Secondary outcomes:
measure: Patient Global Impression of Change (PGIC)
timeFrame: This outcome will be assessed weekly, for up to 44 weeks.
measure: Number needed to treat (NNT)
timeFrame: This outcome will be assessed once, through study completion, an average of 44 weeks.
Other outcomes:
measure: Weekly Symptom Reports
timeFrame: This outcome will be assessed weekly, for up to 44 weeks.
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Jarred Younger, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.