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

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind pilot study of Nicotinamide Riboside (NR) in Pediatric-onset Ulcerative Colitis (UC).

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.

What data supports the effectiveness of the drug Nicotinamide Riboside Chloride for treating ulcerative colitis?

Research on a similar compound, nicotinamide mononucleotide (NMN), shows it can improve intestinal inflammation and gut health in mice with colitis, suggesting potential benefits for similar conditions. Additionally, Nicotinamide Riboside (NR) is known to increase NAD+ levels, which may support cellular health and repair. ^{1 2 3 4 5}

Is nicotinamide riboside safe for human use?

Nicotinamide riboside, a form of vitamin B3, has been studied for safety and is generally recognized as safe for use in foods and supplements. Human studies show no significant safety concerns, and it is considered safe for healthy adults at certain doses, though caution is advised for pregnant and lactating women. ^{4 6 7 8 9}

How does the drug Nicotinamide Riboside Chloride differ from other treatments for ulcerative colitis?

Nicotinamide Riboside Chloride is unique because it is a form of vitamin B3 that boosts NAD+ levels, which is important for various metabolic processes. Unlike traditional treatments for ulcerative colitis, which often focus on reducing inflammation directly, this drug may offer benefits by enhancing cellular energy and metabolism, potentially impacting inflammation indirectly. ^{4 6 10 11 12}

Research Team

Kevin Mollen

Principal Investigator

University of Pittsburgh

Eligibility Criteria

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 am 18 years old or younger.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 (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]

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 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]

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]

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]

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]

References

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

The effect of mesalamine and nicotine in the treatment of inflammatory bowel disease. [2017]

2. Turkey pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Preserves Ovarian Injury in Experimental Sepsis Model in Rats. [2023]

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

Treatment of inflammatory bowel disease: Potential effect of NMN on intestinal barrier and gut microbiota. [2022]

4. 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]

5. Germany pubmed.ncbi.nlm.nih.gov

Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil-specific antibacterial clearance. [2014]

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

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

7. United States 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. [2020]

8. 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]

9. 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]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Identification of Novel Triazole-Based Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors Endowed with Antiproliferative and Antiinflammatory Activity. [2018]

12. Switzerland 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. [2022]