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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Nicotinamide Riboside (NR), a supplement, can boost NAD+ levels in the blood of people with Gulf War Illness (GWI). Participants will receive either NR or a placebo for 10 weeks to assess any differences. The trial targets veterans who served in the Gulf War from 1990 to 1991 and experience chronic GWI symptoms. Ideal candidates are medically stable and have not recently used NR or similar supplements. As an unphased trial, this study provides veterans a unique opportunity to contribute to research that could lead to new insights and potential treatments for GWI.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Nicotinamide Riboside (NR), a type of vitamin B3, is generally safe for people. One study found that participants who took 250 mg of NR daily for 12 weeks tolerated it well, with no major safety issues. The FDA also considers NR safe for certain uses, meaning it meets safety standards when used correctly. Overall, NR has a strong safety record for human use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Nicotinamide Riboside (NR) is unique because it's a form of vitamin B3 that targets cellular energy production and repair, which is different from traditional treatments for Gulf War Syndrome that mainly focus on symptom management, like pain relief or psychological therapy. Researchers are excited about NR because it may address the underlying biological issues by boosting NAD+ levels, potentially improving energy metabolism and reducing inflammation. This novel approach could offer a more comprehensive and direct way to tackle the root causes of the condition, rather than just alleviating symptoms.

What evidence suggests that Nicotinamide Riboside might be an effective treatment for Gulf War Syndrome?

Research has shown that Nicotinamide Riboside (NR) is being explored for its potential to help with Gulf War Illness (GWI) by increasing NAD+ levels in the body. NAD+ plays a crucial role in energy production and cell repair. Some studies suggest that boosting NAD+ might alleviate GWI symptoms, but solid proof remains insufficient. In this trial, one group of participants will receive NR to evaluate its effects on GWI symptoms. NR is known to improve metabolism and protect against certain metabolic issues. While more research is needed to confirm its benefits for GWI, there is hope it could help improve symptoms. ^{1 3 6 7 8}

Who Is on the Research Team?

Nancy Klimas, MD

Principal Investigator

Nova Southeastern University

Amanpreet Cheema, PhD

Principal Investigator

Nova Southeastern University

Laila Abdullah, PhD

Principal Investigator

The Roskamp Institute

Michael Hoffmann, MD

Principal Investigator

The Roskamp Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0161813X20300656

Targeting sirtuin activity with nicotinamide riboside reduces ... Targeting sirtuin activity with NR may represent a new avenue for treating GWI. Abstract. Gulf War Illness (GWI) affects 30% of veterans from the 1991 Gulf War ...

2. withpower.com withpower.com/trial/phase-gulf-war-illness-3-2022-bc3b4

Nicotinamide Riboside for Gulf War Syndrome Therefore, there is no evidence from the provided information to suggest that Nicotinamide Riboside is an effective treatment for Gulf War Syndrome.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10459282/

Nicotinamide Riboside, a Promising Vitamin B3 Derivative for ... Among NAD+ precursors, NR is often suggested as a dietary supplement to enhance oxidative metabolism and protect against HFD-induced obesity and deficient MT ...

4. clinconnect.io clinconnect.io/trials/NCT05243290

Nicotinamide Riboside Clinical Trial for GWI - ClinConnect The goal is to see if taking 300 mg of NR can increase levels of a substance in the blood called NAD+, which may help improve symptoms related to GWI. The trial ...

5. va.gov va.gov/RAC-GWVI/meetings/sep2015/A-Pres2BeatriceGolomb.pdf

Gulf War Illness: Some BioMarker Findings Q100 vs Placebo Benefited Symptoms and Function in GWI. Participants: 46 GWV met Kansas & CDC criteria for GWI.

6. fda.gov fda.gov/files/food/published/GRAS-Notice-000635--Nicotinamide-riboside-chloride.pdf

GRAS Notice 635: Nicotinamide riboside chloride The intake of Niagen from the intended uses specified above has been shown to be safe and GRAS based on generally available and accepted ...

7. mdpi.com mdpi.com/2072-6643/14/19/3889

Emerging Role of Nicotinamide Riboside in Health and ... This recently discovered vitamin, B3, has demonstrated excellent safety and efficacy profiles and is orally bioavailable in humans.

8. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/nicotinamide-riboside

Nicotinamide Riboside - an overview The dietary supplement nicotinamide riboside (NR), a precursor of NAD+ involved in cellular bioenergetics, can cross the BBB following systemic administration.