Nicotinamide Riboside for Ulcerative Colitis

Overseen By Min Shi

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Pittsburgh

Must not be taking: Steroids, Antibiotics

Disqualifiers: Severe ulcerative colitis, Crohn's, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6-12 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether Nicotinamide Riboside, a supplement, can help treat pediatric-onset ulcerative colitis, which causes inflammation in the digestive tract. The study compares the effects of this supplement against a placebo, both administered alongside standard therapy. Suitable candidates for this trial include children and teens with mild to moderate ulcerative colitis who haven't recently used steroids or antibiotics. As an unphased trial, it offers patients the chance to contribute to groundbreaking research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, patients on biologic medications can join if their dose has been stable for at least three months. After starting the study, you can continue any medication as advised by your doctor.

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

Research has shown that Nicotinamide Riboside (NR) is generally safe for people. Studies have found that taking up to 300 mg of NR daily by mouth is likely safe. Side effects are usually mild, such as nausea or fatigue. Importantly, other human studies with NR have reported no serious problems, indicating that NR is well-tolerated and considered safe for healthy adults at certain doses. However, pregnant women should exercise caution. Overall, based on current data, NR appears to be a safe choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for ulcerative colitis, which typically involve anti-inflammatory drugs, immunosuppressants, or biologics, Nicotinamide Riboside Chloride (Niagen) acts by boosting cellular energy production through its role in NAD+ metabolism. This unique mechanism can potentially enhance cellular repair and reduce inflammation in a novel way. Researchers are excited about this treatment because it offers a different approach to managing ulcerative colitis, potentially with fewer side effects and improved gut health.

What evidence suggests that Nicotinamide Riboside might be an effective treatment for Ulcerative Colitis?

Research suggests that Nicotinamide Riboside (NR), which participants in this trial may receive, might help treat Ulcerative Colitis (UC) by boosting the body's natural defenses. Studies have found that NR enhances the function of neutrophils, a type of white blood cell that fights bacteria. This boost might reduce gut inflammation, a key issue in UC. Additionally, animal studies have shown that NR can alter gut bacteria, which might also help manage UC symptoms. These early findings indicate that NR could be a promising treatment for UC by addressing inflammation and improving gut health. ^{4 6 7 8 9}

Who Is on the Research Team?

Kevin Mollen

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

This trial is for children and teenagers (≤18 years old) with mild to moderate ulcerative colitis. It's open to those newly diagnosed or with established disease, but not if they have severe UC, other gastrointestinal infections, Crohn's disease, certain other inflammatory conditions, recent steroid/antibiotic use, or kidney/liver problems.

Inclusion Criteria

Although the investigators will target newly diagnosed patients (therefore, treatment naïve), patients with established disease will also be enrolled

I have been diagnosed with mild to moderate ulcerative colitis.

Exclusion Criteria

I have kidney or liver problems.

My condition is diagnosed as indeterminate colitis or IBD-U.

I am not pregnant and will use contraception if of childbearing age.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 years

Treatment

Participants receive daily oral therapy with either Nicotinamide Riboside Chloride or placebo, alongside standard therapy

6-12 months

Colonoscopic evaluations at enrollment and after 6-12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside Chloride
• Placebo
• Standard of Care

Trial Overview The study tests Nicotinamide Riboside Chloride in young patients with Ulcerative Colitis against a placebo while maintaining standard care. Participants are randomly assigned to either the test drug or placebo without knowing which one they receive.

How Is the Trial Designed?

Group I: Daily oral therapy with placebo + Standard Therapy Experimental Treatment 2 Interventions

Placebo 75mg or 250mg capsules provided by ChromaDex, Inc. Dosing is recommended at 12.5mg/kg/day. The dosing plan is as follows (in mg po qD): 20-25 kg 250mg; 25-30 kg 325mg; 30-35 kg 400mg; 35-40 kg 475mg; 40-45 kg 500mg; 45-50 kg 575mg; 50-55 kg 650mg; 55-60 kg 725mg; 60-65 kg 750mg; 65-70 kg 825mg; \>70 kg 900mg (max dosing).

Group II: Daily oral therapy with Nicotinamide Riboside Chloride (Niagen) + Standard Therapy Experimental Treatment 2 Interventions

Nicotinamide Riboside Chloride (Niagen) 75mg or 250mg capsules provided by ChromaDex, Inc. Dosing is recommended at 12.5mg/kg/day. The dosing plan is as follows (in mg po qD): 20-25 kg 250mg; 25-30 kg 325mg; 30-35 kg 400mg; 35-40 kg 475mg; 40-45 kg 500mg; 45-50 kg 575mg; 50-55 kg 650mg; 55-60 kg 725mg; 60-65 kg 750mg; 65-70 kg 825mg; \>70 kg 900mg (max dosing).

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

Approved in European Union as Nicotinamide Riboside Chloride for:

• Food supplements
• Foods for special medical purposes (FSMP)
• Total Diet Replacements Products for Weight Control (TDRWC)

Approved in United States as Nicotinamide Riboside Chloride for:

• Dietary supplements

Approved in Canada as Nicotinamide Riboside Chloride for:

• Licensed Natural Health Products

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Crohn's and Colitis Foundation

Collaborator

Trials

44

Recruited

27,500+

Published Research Related to This Trial

A novel class of NAMPT inhibitors, particularly compound 30c, has shown strong potential as an antitumoral drug in both xenograft and allograft models, indicating its efficacy in targeting cancer cells.

Compound 30c also significantly improved outcomes in a mouse model of colitis, suggesting that NAMPT inhibitors could have new therapeutic applications beyond cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of Novel Triazole-Based Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors Endowed with Antiproliferative and Antiinflammatory Activity. Travelli, C., Aprile, S., Rahimian, R., et al.[2018]

Mesalamine has been shown to effectively induce remission in patients with active ulcerative colitis, with doses of 2 g/d and 4 g/d outperforming placebo, and rectal mesalamine achieving a 78% remission rate in patients with prior steroid treatment.

In contrast, while mesalamine reduced the relapse rate in inactive Crohn's disease from 71% to 55%, nicotine was found to have adverse effects on Crohn's disease and is not recommended for treatment, indicating that mesalamine is the more reliable option for managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mesalamine and nicotine in the treatment of inflammatory bowel disease. Bonapace, CR., Mays, DA.[2017]

Nicotinamide (NAM) significantly reduced bacterial invasion and histological damage in mice with colitis, showing up to a 600-fold increase in fecal clearance of the bacteria Citrobacter rodentium.

The beneficial effects of NAM were linked to enhanced antimicrobial activity in neutrophils, as it improved bacterial clearance and increased the expression of antimicrobial peptides, indicating its potential for treating intestinal infections and inflammatory bowel disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance. Bettenworth, D., Nowacki, TM., Ross, M., et al.[2014]

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]

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) and its new derivatives, NRTBCl and NRTOCl, were tested in vivo in chickens, showing that NRCl significantly increased beneficial gut bacteria like Bifidobacterium and Lactobacillus, which could enhance gut health.

The treatments also upregulated the expression of important proteins in the intestine, suggesting that NR and its derivatives may improve digestive function and alter gut microbiota composition, warranting further research into their effects on inflammation and specific bacterial populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in Intestinal Brush Border Membrane Functionality and Bacterial Populations Following Intra-Amniotic Administration (Gallus gallus) of Nicotinamide Riboside and Its Derivatives. Kolba, N., Zarei, A., Cheng, J., et al.[2022]

Nicotinamide mononucleotide (NMN) treatment in mice with colitis led to improved intestinal health, including better morphology, reduced inflammation, and enhanced barrier function, indicating its potential efficacy in treating inflammatory bowel disease (IBD).

NMN also positively influenced the gut microbiome by increasing beneficial bacteria like Firmicutes and Lactobacillus while decreasing harmful bacteria, suggesting it may help restore gut flora balance in IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of inflammatory bowel disease: Potential effect of NMN on intestinal barrier and gut microbiota. Huang, P., Wang, X., Wang, S., et al.[2022]

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 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 treatment significantly improved antioxidant enzyme activities and reduced oxidative stress markers in rats with sepsis, indicating its protective effects against oxidative damage.

The treatment also preserved ovarian tissue integrity and reduced inflammation, suggesting that nicotinamide riboside could be a promising therapeutic strategy to prevent sepsis-induced ovarian injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Preserves Ovarian Injury in Experimental Sepsis Model in Rats. Selli, J., Vural Keles, D., Keles, ON., et al.[2023]

Nicotinamide riboside chloride is considered safe for use in food supplements at levels up to 300 mg/day for healthy adults, with no safety concerns raised from human studies or animal data.

The substance effectively contributes to the body's nicotinamide levels and is bioavailable, making it a viable source of niacin, although caution is advised for pregnant and lactating women due to insufficient safety data for these groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nicotinamide riboside chloride as a novel food pursuant to Regulation (EU) 2015/2283 and bioavailability of nicotinamide from this source, in the context of Directive 2002/46/EC. Turck, D., Castenmiller, J., de Henauw, S., et al.[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05561738?term=nicotinamide%20riboside&viewType=Table&rank=4

NCT05561738 | Nicotinamide Riboside in Ulcerative Colitis This is a randomized, double-blind pilot study of Nicotinamide Riboside (NR) in Pediatric-onset Ulcerative Colitis (UC). Detailed Description. The investigators ...

2. withpower.com withpower.com/trial/phase-colitis-2023-d9074

Nicotinamide Riboside for Ulcerative Colitis The beneficial effects of NAM were linked to enhanced antimicrobial activity in neutrophils, as it improved bacterial clearance and increased the expression of ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10070358/

Oral supplementation of nicotinamide riboside alters intestinal ... In conclusion, oral NR altered the gut microbiota in rats and mice, but not in humans. In addition, NR attenuated body fat mass gain in rats, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9385040/

Metabolic analyses reveal dysregulated NAD+ metabolism ... These findings suggest a link between mitochondrial dysfunction, inflammation, and NAD + metabolism in UC.

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05561738/

Trial | NCT05561738 This is a randomized, double-blind pilot study of Nicotinamide Riboside (NR) in Pediatric-onset Ulcerative Colitis (UC). The investigators hypothesize that NR ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05561738

NCT05561738 | Nicotinamide Riboside in Ulcerative Colitis This is a randomized, double-blind pilot study of Nicotinamide Riboside (NR) in Pediatric-onset Ulcerative Colitis (UC). Detailed Description. The investigators ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-1560/nicotinamide-riboside

NICOTINAMIDE RIBOSIDE – Uses, Side Effects, and More When taken by mouth: Nicotinamide riboside chloride is possibly safe when used in doses up to 300 mg daily. Side effects are usually mild and might include ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6611812/

Safety and Metabolism of Long-term Administration of ... NIAGEN is generally recognized as safe, with no significant adverse events reported. It does not elevate LDL cholesterol, and doses up to 1 ...

9. 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 ...