- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05561738
Nicotinamide Riboside in Ulcerative Colitis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The investigators hypothesize that NR will alleviate mitochondrial dysfunction and restore metabolic homeostasis in the intestinal epithelium in pediatric patients with UC.
The purpose of the study are:
- To establish the feasibility of an Randomized Clinical Trial (RCT) investigating the effects of NR in pediatric patients with UC.
- To evaluate the effects of Nicotinamide adenine dinucleotide (NAD)+ repletion on intestinal epithelial mitochondrial structure and function in human UC patients. The investigators hypothesize that daily NR supplementation will restore NAD+ levels, enhancing Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) activity and mitochondrial structure/function.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Min Shi
- Phone Number: 412-692-6272
- Email: shim@upmc.edu
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15224
- Recruiting
- UPMC Children's Hospital of Pittsburgh
-
Contact:
- Min Shi
- Email: shim@upmc.edu
-
Principal Investigator:
- Kevin P Mollen, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Pediatric patients (≤18yo);
- Diagnosis of mild to moderate ulcerative colitis as determined by Pediatric Ulcerative Colitis Activity Index (PUCAI) and endoscopic scoring (Mayo) at the time of colonoscopy;
- Although the investigators will target newly diagnosed patients (therefore, treatment naïve), patients with established disease will also be enrolled.
Exclusion Criteria:
- Patients with acute severe ulcerative colitis;
- Concurrent gastrointestinal infection (ie. Clostridium difficile, Cytomegalovirus, etc.);
- A diagnosis of Crohn's disease;
- Indeterminate colitis/IBD-U;
- In general, patients that have been treated with steroids or antibiotics in the past three months. Patients on Biologic medications may be enrolled if their dose has been stable for at least three months. Final determination of eligibility will be at the discretion of the treating investigator. After the initiation of the study, subjects may receive any medication to treat their disease as dictated by their care providers;
- Patients who have other chronic inflammatory/autoimmune disorders or prior malignancy;
- Pregnant women (All women of childbearing age will be required to use contraception at the time of inclusion).
- Patients with existing renal or hepatic dysfunction;
- Per standard of care guidance, subjects with platelets <50,000 do not undergo endoscopy and, therefore, are not eligible.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Daily oral therapy with Nicotinamide Riboside Chloride (Niagen) + Standard Therapy
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). |
Standard of Care
The intervention consists of 6 months to 1 year of daily oral therapy with Nicotinamide Riboside Chloride (Niagen) in addition to standard therapy.
|
Experimental: Daily oral therapy with placebo + Standard Therapy
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). |
Standard of Care
The intervention consists of 6 months to 1 year of daily oral therapy with placebo (Maltodextran capsules of similar size, shape and color as Niagen) in addition to standard therapy.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients screened
Time Frame: 2 years
|
The investigators will report the number of overall patients screened for enrollment.
|
2 years
|
Proportion of patients screened who meet inclusion/exclusion criteria
Time Frame: 2 years
|
The investigators will report the number of patients screened who meet inclusion/exclusion criteria.
|
2 years
|
Enrollment percentage
Time Frame: 2 years
|
The investigators will report the proportion of eligible patients who enroll in the study per month.
|
2 years
|
Completion percentage
Time Frame: 2 years
|
The investigators will report the proportion of enrolled subjects who complete the study.
|
2 years
|
Reasons for exclusion
Time Frame: 2 years
|
The investigators will report the reasons that patients are excluded from the study.
|
2 years
|
Dropout rate
Time Frame: 2 years
|
The investigators will report the percentage of subjects who drop out per month.
|
2 years
|
Reasons for dropout
Time Frame: 2 years
|
The investigators will log reasons for dropout.
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in mitochondrial structure from baseline to 6-12 months
Time Frame: Baseline 6-12 months
|
Subjects will undergo colonoscopic evaluation at enrollment and after 6-12 months of treatment (per standard treatment protocols).
Investigators will perform a qualitative analysis of mitochondrial structure using scanning electron microscopy and/or immunofluorescence at both timepoints.
|
Baseline 6-12 months
|
Changes in mitochondrial function from baseline to 6-12 months
Time Frame: Baseline 6-12 months
|
Subjects will undergo colonoscopic evaluation at enrollment and after 6-12 months of treatment (per standard treatment protocols).
Investigators will evaluate mitochondrial function (Complex 1 and 2) via the Oroboros 2K Analyzer [oxygen consumption [(pmol/(s × mL)/μg protein] at both timepoints.
|
Baseline 6-12 months
|
Changes in the PGC1α-Sirt1 axis from baseline to 6-12 months
Time Frame: Baseline 6-12 months
|
Subjects will undergo colonoscopic evaluation at enrollment and after 6-12 months of treatment (per standard treatment protocols).
PGC1α and Sirt1 levels will be evaluated in tissue biopsies using western blot (qualitative analysis of protein levels) and qRT-PCR analysis (quantitative gene expression in fold change) at both timepoints.
|
Baseline 6-12 months
|
Changes in cellular metabolism from baseline to 6-12 months
Time Frame: Baseline 6-12 months
|
Subjects will undergo colonoscopic evaluation at enrollment and after 6-12 months of treatment (per standard treatment protocols).
An untargeted metabolomic analysis of the intestinal epithelium will be performed at these time points (fold change) at both timepoints.
|
Baseline 6-12 months
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kevin Mollen, University of Pittsburgh
Publications and helpful links
General Publications
- Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948. doi: 10.1038/ncomms12948.
- Novak EA, Mollen KP. Mitochondrial dysfunction in inflammatory bowel disease. Front Cell Dev Biol. 2015 Oct 1;3:62. doi: 10.3389/fcell.2015.00062. eCollection 2015.
- Cunningham KE, Vincent G, Sodhi CP, Novak EA, Ranganathan S, Egan CE, Stolz DB, Rogers MB, Firek B, Morowitz MJ, Gittes GK, Zuckerbraun BS, Hackam DJ, Mollen KP. Peroxisome Proliferator-activated Receptor-gamma Coactivator 1-alpha (PGC1alpha) Protects against Experimental Murine Colitis. J Biol Chem. 2016 May 6;291(19):10184-200. doi: 10.1074/jbc.M115.688812. Epub 2016 Mar 11.
- Haberman Y, Karns R, Dexheimer PJ, Schirmer M, Somekh J, Jurickova I, Braun T, Novak E, Bauman L, Collins MH, Mo A, Rosen MJ, Bonkowski E, Gotman N, Marquis A, Nistel M, Rufo PA, Baker SS, Sauer CG, Markowitz J, Pfefferkorn MD, Rosh JR, Boyle BM, Mack DR, Baldassano RN, Shah S, Leleiko NS, Heyman MB, Grifiths AM, Patel AS, Noe JD, Aronow BJ, Kugathasan S, Walters TD, Gibson G, Thomas SD, Mollen K, Shen-Orr S, Huttenhower C, Xavier RJ, Hyams JS, Denson LA. Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response. Nat Commun. 2019 Jan 3;10(1):38. doi: 10.1038/s41467-018-07841-3.
- Larmonier CB, Shehab KW, Laubitz D, Jamwal DR, Ghishan FK, Kiela PR. Transcriptional Reprogramming and Resistance to Colonic Mucosal Injury in Poly(ADP-ribose) Polymerase 1 (PARP1)-deficient Mice. J Biol Chem. 2016 Apr 22;291(17):8918-30. doi: 10.1074/jbc.M116.714386. Epub 2016 Feb 24.
- Santos L, Escande C, Denicola A. Potential Modulation of Sirtuins by Oxidative Stress. Oxid Med Cell Longev. 2016;2016:9831825. doi: 10.1155/2016/9831825. Epub 2015 Dec 14.
- Gerner RR, Klepsch V, Macheiner S, Arnhard K, Adolph TE, Grander C, Wieser V, Pfister A, Moser P, Hermann-Kleiter N, Baier G, Oberacher H, Tilg H, Moschen AR. NAD metabolism fuels human and mouse intestinal inflammation. Gut. 2018 Oct;67(10):1813-1823. doi: 10.1136/gutjnl-2017-314241. Epub 2017 Sep 6.
- Mehmel M, Jovanovic N, Spitz U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients. 2020 May 31;12(6):1616. doi: 10.3390/nu12061616.
- Jiang Y , Liu Y , Gao M , Xue M , Wang Z , Liang H . Nicotinamide riboside alleviates alcohol-induced depression-like behaviours in C57BL/6J mice by altering the intestinal microbiota associated with microglial activation and BDNF expression. Food Funct. 2020 Jan 29;11(1):378-391. doi: 10.1039/c9fo01780a.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Gastrointestinal Diseases
- Gastroenteritis
- Colonic Diseases
- Intestinal Diseases
- Inflammatory Bowel Diseases
- Ulcer
- Colitis
- Colitis, Ulcerative
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Antimetabolites
- Micronutrients
- Hypolipidemic Agents
- Lipid Regulating Agents
- Vitamins
- Vitamin B Complex
- Nicotinic Acids
- Niacinamide
- Niacin
Other Study ID Numbers
- STUDY22060104
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
Prior to any sharing of any data, the research data/documents will be coded and all subject identifiers will be completely removed. Only the PI and co-investigators will have access to the coding. All others will have access to the completely deidentified data only.
A data use agreement will be obtained and finalized prior to any of the data leaving the institution, and prior to any access by outside entities.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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