Natural Supplements for Gulf War Syndrome

Overseen By Catherine Burley

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Anticoagulants, Lithium, Tacrolimus, Cancer meds

Disqualifiers: Pregnancy, Diabetes, Blood clotting, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 32 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications to join this trial. Specifically, if you are on anticoagulants (blood thinners), lithium, tacrolimus, or certain cancer medications, you cannot participate.

Is turmeric (Curcuma longa) safe for human use?

Turmeric, particularly its active component curcumin, is generally considered safe for human use. It is well-tolerated with common side effects being mild, such as nausea and diarrhea. Studies have shown that certain turmeric extracts are safe at specific doses, but caution is advised when used with chemotherapy agents. ^{1 2 3 4 5}

How is the treatment for Gulf War Syndrome using natural supplements unique?

This treatment is unique because it uses natural supplements like curcumin, resveratrol, and stinging nettle, which have anti-inflammatory and antioxidant properties. These supplements target multiple pathways in the body, potentially offering a broader approach to managing symptoms compared to conventional treatments that may focus on a single target. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment for Gulf War Syndrome?

Curcumin, a key component of the treatment, has shown anti-inflammatory and antioxidant properties, which have been beneficial in treating various chronic diseases, including diabetes and cancer. These properties suggest potential effectiveness in managing symptoms of Gulf War Syndrome, which may involve inflammation and oxidative stress. ^{6 7 11 12 13}

Who Is on the Research Team?

Jarred Younger, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for individuals with Gulf War Illness who can commit to a 10-month study and meet specific GWI case definitions. It's not suitable for those in other experimental studies, with abnormal liver or kidney function, pregnant women, or people with blood clotting disorders or on antiplatelet/anticoagulant medications.

Inclusion Criteria

Meets CDC GWI Case Definition

Meets Kansas GWI Case Definition

Able to commit to a 10-month study

Exclusion Criteria

I have a blood clotting disorder.

Currently involved in an experimental treatment study

Currently pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Online screening survey and Zoom meeting

Baseline

Participants complete baseline questionnaires and begin weekly symptom severity reports and primary outcome measures

4 weeks

Remote setup and baseline assessments

Treatment

Participants take assigned botanical capsules and complete weekly symptom reports and outcome assessments

32 weeks

Remote monitoring and weekly online surveys

Endline

Participants complete endline measurements and are debriefed

4 weeks

Remote endline assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Curcumin
• Resveratrol
• Stinging Nettle

Trial Overview The trial is testing the effectiveness of curcumin, resveratrol, and stinging nettle as treatments for GWI. Participants from across the U.S. can join this decentralized study without geographic restrictions.

How Is the Trial Designed?

Group I: Gulf War Veterans, Stinging Nettle Experimental Treatment 1 Intervention

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 II: Gulf War Veterans, Resveratrol Experimental Treatment 1 Intervention

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 III: Gulf War Veterans, Curcumin Experimental Treatment 1 Intervention

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.

Curcumin is already approved in United States, European Union, India, China for the following indications:

Approved in United States as Curcumin for:

• Dietary Supplement

Approved in European Union as Curcuma for:

• Herbal Medicinal Product

Approved in India as Haldi for:

• Traditional Medicine

Approved in China as Jiang Huang for:

• Traditional Chinese Medicine

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Published Research Related to This Trial

Curcumin, the active compound in turmeric, has shown significant therapeutic properties, including anti-inflammatory, antioxidant, and cancer preventive effects, making it a promising treatment for chronic diseases like diabetes mellitus.

Despite its potential benefits, curcumin's low solubility in water limits its bioavailability, which poses challenges for its use as a therapeutic agent; ongoing research aims to improve its solubility and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CURCUMA LONGA AS MEDICINAL HERB IN THE TREATMENT OF DIABET- IC COMPLICATIONS. Karlowicz-Bodalska, K., Han, S., Freier, J., et al.[2018]

Curcumin, a compound found in turmeric, has been shown to effectively reduce inflammation by targeting key inflammatory factors and enzymes, making it a potential treatment for various chronic diseases.

Research has explored the pharmacodynamics and pharmacokinetics of curcumin in both animals and humans, highlighting its broad therapeutic potential across multiple health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Aggarwal, BB., Sung, B.[2022]

FITOPROT, a mucoadhesive formulation containing curcuminoids and extracts from Bidens pilosa, effectively protects HaCaT cells from toxicity induced by the chemotherapy drug 5-FU, demonstrating its potential as a chemopreventive agent.

The formulation works by reducing oxidative stress and inflammation, preventing mitochondrial damage, and restoring cell proliferation, indicating its mechanism of action involves antioxidant and anti-inflammatory pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemopreventive effects of FITOPROT against 5-fluorouracil-induced toxicity in HaCaT cells. Dos Santos Filho, EX., da Silva, ACG., de Ávila, RI., et al.[2018]

Spice-derived nutraceuticals, such as curcumin and capsaicin, have shown potential in preventing and treating cancer by targeting multiple gene products and modulating various biological pathways, including transcription factors and inflammatory mediators.

These natural products, traditionally used for culinary and preservative purposes, are gaining recognition for their therapeutic benefits against chronic diseases, particularly cancer, highlighting their role in both prevention and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer cell signaling pathways targeted by spice-derived nutraceuticals. Sung, B., Prasad, S., Yadav, VR., et al.[2021]

In a pilot study involving 74 head and neck cancer patients undergoing radiotherapy, a 0.1% curcumin mouthwash significantly delayed the onset of radiation-induced oral mucositis (RIOM) by about 2 weeks compared to a 0.15% benzydamine mouthwash, with a 50% lower risk of developing RIOM.

While both mouthwashes were found to be equally effective in preventing severe forms of RIOM, neither was able to completely prevent its onset, indicating that curcumin may offer some benefits in managing this common side effect of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of curcumin mouthwash on radiation-induced oral mucositis among head and neck cancer patients: A triple-blind, pilot randomised controlled trial. Shah, S., Rath, H., Sharma, G., et al.[2022]

Quercetin-decorated liposomes containing curcumin showed improved effectiveness in increasing the lifespan and body weight of mice with Dalton's ascites lymphoma compared to liposomes without quercetin, indicating enhanced therapeutic potential.

The study demonstrated that these liposomes, with a particle size of approximately 261.8 nm, not only improved the cytotoxicity against cancer cells (HT-29 and HCT-15) but also addressed curcumin's limitations like poor solubility and short biological half-life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quercetin-Decorated Curcumin Liposome Design for Cancer Therapy: In-Vitro and In-Vivo Studies. Ravichandiran, V., Masilamani, K., Senthilnathan, B., et al.[2018]

Turmeric, particularly its active component curcumin, exhibits a wide range of beneficial biological activities, including anti-inflammatory, antioxidant, and anticancer effects, making it a promising candidate for clinical research.

The review highlights the safety profile of turmeric, suggesting it has low toxicity, which supports its use as a natural treatment option for various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemistry, Safety, Pharmacological Activities, and Clinical Applications of Turmeric: A Mechanistic Review. Ahmad, RS., Hussain, MB., Sultan, MT., et al.[2020]

Tetrahydrocurcuminoids from turmeric have been evaluated and deemed safe for consumption at a maximum level of 140 mg/day for adults, which is lower than the proposed dose of 300 mg/day.

The evaluation included a 90-day oral toxicity study and showed no concerns regarding genotoxicity, indicating that tetrahydrocurcuminoids do not pose significant health risks when consumed within the established safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2022]

CuminUP60®, a curcumin complex derived from Curcuma longa L., demonstrated no mutagenic effects in various safety studies, indicating it is safe for use.

In toxicity studies involving Sprague-Dawley rats, a single dose of 5000 mg was well tolerated, and the no observed adverse effect level (NOAEL) was established at 1000 mg/kg bw/day over a 4-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of CuminUP60® - A novel curcumin complex. Dziwenka, M., Li, X., Li, W., et al.[2022]

Curcumin, the active component of turmeric, has shown promising anti-inflammatory and antineoplastic effects in preclinical studies, with early human trials indicating potential benefits for various conditions such as inflammatory bowel disease and rheumatoid arthritis.

Curcumin is generally well-tolerated, with mild side effects like nausea and diarrhea, but caution is advised regarding its interactions with chemotherapy agents, highlighting the need for further late-phase clinical trials to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of curcumin extract. Asher, GN., Spelman, K.[2013]

Curcumin, the active component of turmeric, has been shown to effectively modulate various molecular targets involved in inflammation and disease, making it a potential treatment for conditions like cancer, arthritis, and diabetes.

The safety and cost-effectiveness of curcumin and its analogs, such as 6-gingerol from ginger, support their use in traditional medicine and modern therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin: getting back to the roots. Shishodia, S., Sethi, G., Aggarwal, BB.[2022]

Curcuma longa, commonly known as turmeric, is a medicinal herb with a long history of use in traditional Chinese and Ayurvedic medicine for its anti-inflammatory properties and treatment of various ailments.

Current research highlights turmeric's potential health benefits, including its antioxidant, hepatoprotective, and antimicrobial effects, making it relevant for conditions like cardiovascular disease and gastrointestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcuma longa (turmeric). Monograph. [2022]

Curcumin, the active compound in turmeric, has demonstrated a wide range of therapeutic effects, including antioxidant, anti-inflammatory, and anticancer properties, making it potentially beneficial for various chronic diseases such as diabetes, arthritis, and Alzheimer's disease.

Research indicates that curcumin's effects are mediated through the regulation of key biological pathways, similar to those targeted by modern medications like tumor necrosis factor blockers and growth factor inhibitors, suggesting its role as a multitargeted therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin: the Indian solid gold. Aggarwal, BB., Sundaram, C., Malani, N., et al.[2022]

Citations

1. Poland pubmed.ncbi.nlm.nih.gov

CURCUMA LONGA AS MEDICINAL HERB IN THE TREATMENT OF DIABET- IC COMPLICATIONS. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Chemopreventive effects of FITOPROT against 5-fluorouracil-induced toxicity in HaCaT cells. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Cancer cell signaling pathways targeted by spice-derived nutraceuticals. [2021]

5. India pubmed.ncbi.nlm.nih.gov

Effectiveness of curcumin mouthwash on radiation-induced oral mucositis among head and neck cancer patients: A triple-blind, pilot randomised controlled trial. [2022]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Quercetin-Decorated Curcumin Liposome Design for Cancer Therapy: In-Vitro and In-Vivo Studies. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Biochemistry, Safety, Pharmacological Activities, and Clinical Applications of Turmeric: A Mechanistic Review. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Safety evaluation of CuminUP60® - A novel curcumin complex. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical utility of curcumin extract. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Curcumin: getting back to the roots. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Curcuma longa (turmeric). Monograph. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Curcumin: the Indian solid gold. [2022]