Nicotinamide Riboside for Gulf War Syndrome

Recruiting at 1 trial location

Overseen By Dakota Helgager

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Roskamp Institute Inc.

Must not be taking: NR supplements

Disqualifiers: Pregnancy, Nursing, Hypertension, Renal failure, others

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

52 Participants Needed

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but 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 Nicotinamide Riboside safe for human use?

Nicotinamide Riboside (NR) has been studied in humans and animals, showing it is generally safe at various doses. In human trials, NR did not cause significant side effects compared to a placebo, and in animal studies, it showed no severe toxicity at tested doses. However, more research is needed to confirm its safety at very high doses. ^{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}

How does the drug Nicotinamide Riboside differ from other treatments for Gulf War Syndrome?

Nicotinamide Riboside is unique because it is a form of vitamin B3 that may help boost cellular energy production and repair, which is different from other treatments that focus on detoxification or reducing inflammation. This approach is novel as it targets the underlying cellular processes rather than just alleviating symptoms. ^{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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 300 mg of Nicotinamide Riboside or placebo daily for 10 weeks

10 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotinamide Riboside
• Placebo

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).

Nicotinamide Riboside is already approved in United States, European Union for the following indications:

Approved in United States as Niagen for:

• Dietary supplement for general health and wellness

Approved in European Union as Niagen for:

• Dietary supplement for general health and wellness

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+

Nova Southeastern University

Collaborator

Trials

103

Recruited

12,000+

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 an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.

The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.

NCBI (Pubmed)

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. Conze, D., Brenner, C., Kruger, CL.[2023]

Nicotinamide riboside (NR), a form of vitamin B3, was found to be safe in various toxicity studies, including a 90-day rat study, with no genotoxic effects and no mortality at high doses (5000 mg/kg).

The lowest observed adverse effect level for NR was determined to be 1000 mg/kg/day, indicating that while it is generally safe, higher doses may lead to toxicity in organs such as the liver and kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. Conze, DB., Crespo-Barreto, J., Kruger, CL.[2019]

Nicotinamide riboside (NR) is a promising NAD+ precursor that has shown potential health benefits in treating various conditions, including cardiovascular, neurodegenerative, and metabolic disorders, based on numerous animal and human studies.

Research indicates that NR may also have therapeutic applications against infections, such as SARS-CoV-2, but challenges related to its bioavailability and safety need to be addressed for effective translation into clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Mehmel, M., Jovanović, N., Spitz, U.[2021]

Nicotinamide riboside (NR) is a form of vitamin B3 that effectively increases NAD+ levels, which may help counteract age-related declines in this important metabolite.

In a 90-day safety study on Sprague Dawley rats, NR-E showed no significant adverse effects at doses up to 1,200 mg/kg/d, establishing a no-observed-adverse-effect-level (NOAEL) of 500 mg/kg/d for males and 1,200 mg/kg/d for females.

NCBI (Pubmed)

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. Marinescu, AG., Chen, J., Holmes, HE., et al.[2021]

The EFSA Panel concluded that the safety of nicotinamide riboside chloride (NRC) has not been established for use in meal replacement products and nutritional drink mixes at proposed levels of 300 mg/day, due to concerns about potential adverse effects, especially in infants.

For food for special medical purposes and total diet replacement for weight control, NRC is considered as safe as pure nicotinamide at a maximum intake of 210 mg/day, which is below the established upper limit of 900 mg/day for adults, but further research is needed to assess long-term safety and potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extension of use of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2021]

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]