Clinical trial NCT05561738: Nicotinamide Riboside in Ulcerative Colitis
Official title: Nicotinamide Riboside in Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ulcerative Colitis
Keywords: NAD
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Crohn's and Colitis Foundation
First posted: 2022-09-30
Enrollment: 40
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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

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:

1. To establish the feasibility of an Randomized Clinical Trial (RCT) investigating the effects of NR in pediatric patients with UC.
2. 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients screened
timeFrame: 2 years
measure: Proportion of patients screened who meet inclusion/exclusion criteria
timeFrame: 2 years
measure: Enrollment percentage
timeFrame: 2 years
measure: Completion percentage
timeFrame: 2 years
measure: Reasons for exclusion
timeFrame: 2 years
measure: Dropout rate
timeFrame: 2 years
measure: Reasons for dropout
timeFrame: 2 years
Secondary outcomes:
measure: Changes in mitochondrial structure from baseline to 6-12 months
timeFrame: Baseline 6-12 months
measure: Changes in mitochondrial function from baseline to 6-12 months
timeFrame: Baseline 6-12 months
measure: Changes in the PGC1α-Sirt1 axis from baseline to 6-12 months
timeFrame: Baseline 6-12 months
measure: Changes in cellular metabolism from baseline to 6-12 months
timeFrame: Baseline 6-12 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Kevin Mollen
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
citation: 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.
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