Nicotinamide Riboside for Gulf War Syndrome

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Nancy Klimas, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Roskamp Institute Inc.

Trial Summary

What is the purpose of this trial?

This trial tests whether taking Nicotinamide Riboside (NR), a form of vitamin B3, can help veterans with Gulf War Illness (GWI). GWI causes symptoms like fatigue and pain, possibly due to low energy levels in cells. NR aims to increase a molecule called NAD+ in the blood, which is crucial for cell energy production. The goal is to see if this can improve the health and well-being of these veterans. Nicotinamide Riboside (NR) is a newly discovered nicotinamide adenine dinucleotide (NAD+) precursor vitamin, recognized as safe for use in foods and dietary supplements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use any NR supplement products like nicotinamide or vitamin B3 within 30 days of screening.

What data supports the idea that Nicotinamide Riboside for Gulf War Syndrome is an effective drug?

The available research does not provide any data supporting the effectiveness of Nicotinamide Riboside for Gulf War Syndrome. The studies mentioned focus on other conditions like Guillain-Barré syndrome and do not mention Nicotinamide Riboside. Therefore, there is no evidence from the provided information to suggest that Nicotinamide Riboside is an effective treatment for Gulf War Syndrome. ^{1 2 3 4 5}

What safety data exists for Nicotinamide Riboside?

Nicotinamide Riboside (NR) has been studied for safety in various contexts. In a clinical trial with healthy overweight adults, NR was found to significantly increase NAD+ levels without significant adverse events compared to placebo. Animal studies showed NR is not genotoxic and has a similar toxicity profile to nicotinamide, with target organs of toxicity being the liver, kidney, ovaries, and testes. The no observed adverse effect level (NOAEL) was 300 mg/kg/day in rats. The European Food Safety Authority (EFSA) considers NR safe for certain uses but notes potential adverse effects at high intakes, suggesting further investigation is needed. ^{6 7 8 9 10}

Is the drug Nicotinamide Riboside a promising treatment for Gulf War Syndrome?

The provided research articles do not mention Nicotinamide Riboside as a treatment for Gulf War Syndrome, so there is no information to suggest it is promising. ^{11 12 13 14 15}

Research Team

Nancy Klimas, MD

Principal Investigator

Nova Southeastern University

Laila Abdullah, PhD

Principal Investigator

The Roskamp Institute

Michael Hoffmann, MD

Principal Investigator

The Roskamp Institute

Amanpreet Cheema, PhD

Principal Investigator

Nova Southeastern University

Eligibility Criteria

This trial is for Gulf War veterans aged 47-70 with Gulf War Illness, who are medically stable and not on certain supplements. Women must use birth control if of childbearing potential. Those with allergies to the study drug or significant health issues can't participate.

Inclusion Criteria

I am a veteran diagnosed with Gulf War Illness according to CDC or Kansas criteria.

My weight is between 110 lbs and 440 lbs.

Veterans deployed to the Gulf War between August 1990 and August 1991

Exclusion Criteria

Poor venous access

Clinically significant lab values for clinical laboratory assessments, as per investigator discretion

I am allergic to NR, vitamin B3, or certain pill ingredients.

Treatment Details

Interventions

• Nicotinamide Riboside (Vitamin)
• Placebo (Dietary Supplement)

Trial Overview The trial tests if Nicotinamide Riboside (NR) increases plasma NAD+ levels in GWI patients using a double-blind method where neither participants nor researchers know who gets NR or placebo until after results are collected.

Participant Groups

Group I: Study Supplement: NR Active Control 1 Intervention

26 subjects will take the supplement (nicotinamide riboside) during the first phase of the study. 300mg will be taken once a day for the 10-week period in phase one.

Group II: Control Placebo Group 1 Intervention

26 subjects will take the placebo during the first phase of the study (10 weeks).

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Nova Southeastern University Fort Lauderdale, FL

The Roskamp Institute Sarasota, FL

Who Is Running the Clinical Trial?

Roskamp Institute Inc.

Lead Sponsor

Trials

8

Recruited

930+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Nova Southeastern University

Collaborator

Trials

103

Recruited

12,000+

Dr. George L. Hanbury II

Nova Southeastern University

Chief Executive Officer since 2011

PhD in Higher Education Administration from Nova Southeastern University

Dr. Gary S. Margules

Nova Southeastern University

Chief Medical Officer since 2010

MD from University of Miami

Findings from Research

Guillain-Barré syndrome is an autoimmune disease with a standard treatment of intravenous immunoglobulin (0.4 g/kg/day for five days) or plasma exchange, but about 10% of patients still face severe outcomes, highlighting the need for new therapies.

Current research suggests that while targeting the immune response could lead to new treatments, many potential therapies may not be practical due to their broad immunosuppressive effects, and a better understanding of the disease's pathogenesis is necessary for developing specific immune therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic approaches to Guillain-Barré syndrome. Pritchard, J.[2019]

Decitabine (DAC), a drug known for its immunomodulatory effects, showed promise in improving the clinical outcomes of Guillain-Barré syndrome (GBS) in rodent models, suggesting its potential as a treatment option.

Both preventive and therapeutic administration of DAC increased regulatory T cells and decreased pro-inflammatory cytokines, indicating a beneficial mechanism of action in managing GBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis. Fagone, P., Mazzon, E., Chikovani, T., et al.[2019]

In a 12-month study involving 76 patients with chronic neuromuscular diseases, treatment with purified bovine brain gangliosides (Cronassial) at doses of 40 mg and 100 mg did not demonstrate therapeutic efficacy compared to placebo.

The analysis revealed that several measures of neuromuscular function improved during prolonged placebo treatment, indicating a significant placebo effect that may confound the results of objective assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind controlled trials of Cronassial in chronic neuromuscular diseases and ataxia. Bradley, WG., Badger, GJ., Tandan, R., et al.[2019]

In a systematic review of randomized trials involving 585 adults with Guillain-Barré syndrome, plasma exchange (PE) significantly improved disability scores compared to no treatment, indicating its efficacy as an immunotherapy option.

Intravenous immunoglobulin (IVIg) showed similar effectiveness to PE, but corticosteroids did not provide significant benefits over placebo, suggesting that PE and IVIg are more effective treatments for GBS than corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for Guillain-Barré syndrome: a systematic review. Hughes, RA., Swan, AV., Raphaël, JC., et al.[2022]

In a study of 46 Guillain-Barre Syndrome patients, those receiving prednisolone (a corticosteroid) showed slower improvement in disability compared to the placebo group, taking twice as long to improve by one disability grade.

At 6 months, a higher percentage of patients in the placebo group (54.5%) achieved nearly complete recovery compared to those treated with corticosteroids (41.7%), suggesting that corticosteroids may not only be ineffective but could potentially delay recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do corticosteroids influence the disease course or mortality in Guillain-Barre' syndrome? Singh, NK., Gupta, A.[2013]

In a clinical trial involving 29 men with Gulf War Illness, higher doses of stinging nettle significantly reduced symptom severity, while lower doses did not show any benefit.

Reishi mushroom may worsen symptoms in some patients, and epimedium showed no significant effect on symptom severity, indicating that not all botanical treatments are beneficial for GWI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Younger, J., Donovan, EK., Hodgin, KS., et al.[2021]

Chronic exposure to corticosterone (CORT) can significantly enhance the neuroinflammatory response to diisopropyl fluorophosphate (DFP), a nerve agent surrogate, suggesting that stressors experienced by Gulf War veterans may prime the central nervous system (CNS) for exaggerated inflammatory reactions.

Prophylactic treatments like pyridostigmine bromide (PB) and DEET can reduce DFP-induced neuroinflammation, but their protective effects are diminished when combined with high levels of CORT, indicating a complex interaction between stress, medication, and neuroinflammatory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticosterone primes the neuroinflammatory response to DFP in mice: potential animal model of Gulf War Illness. O'Callaghan, JP., Kelly, KA., Locker, AR., et al.[2018]

A pilot study involving 32 Gulf War veterans tested a detoxification intervention that included exercise, sauna sweating, and supplements, showing it was feasible and safe with no serious adverse events reported.

Participants who underwent the intervention experienced significant improvements in quality of life, pain, and fatigue, with many benefits lasting for at least three months after the program ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial. Kerr, K., Morse, G., Graves, D., et al.[2023]

In a trial with 17 subjects suffering from Gulf War Illness, KPAX002, a combination of methylphenidate and a micronutrient formula, led to a significant 25% reduction in overall symptom severity after 12 weeks (p < 0.001).

The treatment also significantly improved specific symptoms such as fatigue, cognitive issues, sleep problems, and pain, while showing an acceptable safety profile, suggesting it could be a promising option for managing GWI symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment for Gulf War Illness (GWI) with KPAX002 (methylphenidate hydrochloride + GWI nutrient formula) in subjects meeting the Kansas case definition: A prospective, open-label trial. Holodniy, M., Kaiser, JD.[2020]

Gulf War illnesses (GWI) and chronic fatigue syndrome (CFS) may share similar underlying mechanisms related to chronic immune system processes, potentially triggered by the drug pyridostigmine bromide (PB) used during the Gulf War.

Pyridostigmine bromide is linked to neuronal damage through reactive oxygen species (ROS), which may lead to autoimmune responses, suggesting that GWI could be an autoimmune condition resulting from ROS-induced modifications of native molecules.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gulf War illnesses are autoimmune illnesses caused by reactive oxygen species which were caused by nerve agent prophylaxis. Moss, JI.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Novel therapeutic approaches to Guillain-Barré syndrome. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis. [2019]

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

Double-blind controlled trials of Cronassial in chronic neuromuscular diseases and ataxia. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Immunotherapy for Guillain-Barré syndrome: a systematic review. [2022]

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

Do corticosteroids influence the disease course or mortality in Guillain-Barre' syndrome? [2013]

6. England pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. [2021]

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

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. [2021]

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

Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

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). [2021]

12. England pubmed.ncbi.nlm.nih.gov

Corticosterone primes the neuroinflammatory response to DFP in mice: potential animal model of Gulf War Illness. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

A Detoxification Intervention for Gulf War Illness: A Pilot Randomized Controlled Trial. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Treatment for Gulf War Illness (GWI) with KPAX002 (methylphenidate hydrochloride + GWI nutrient formula) in subjects meeting the Kansas case definition: A prospective, open-label trial. [2020]

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

Gulf War illnesses are autoimmune illnesses caused by reactive oxygen species which were caused by nerve agent prophylaxis. [2013]