This is a randomized, double-blind pilot study of Nicotinamide Riboside (NR) in Pediatric-onset Ulcerative Colitis (UC).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE
Enrollment
19
The intervention consists of 6 months to 1 year of daily oral therapy with Nicotinamide Riboside Chloride (Niagen) in addition to standard therapy.
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.
Standard of Care
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
Number of patients screened
The investigators will report the number of overall patients screened for enrollment.
Time frame: 2 years
Proportion of patients screened who meet inclusion/exclusion criteria
The investigators will report the number of patients screened who meet inclusion/exclusion criteria.
Time frame: 2 years
Enrollment percentage
The investigators will report the proportion of eligible patients who enroll in the study per month.
Time frame: 2 years
Completion percentage
The investigators will report the proportion of enrolled subjects who complete the study.
Time frame: 2 years
Reasons for exclusion
The investigators will report the reasons that patients are excluded from the study.
Time frame: 2 years
Dropout rate
The investigators will report the percentage of subjects who drop out per month.
Time frame: 2 years
Reasons for dropout
The investigators will log reasons for dropout.
Time frame: 2 years
Changes in mitochondrial structure from baseline to 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.
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Time frame: Baseline 6-12 months
Changes in mitochondrial function from baseline to 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.
Time frame: Baseline 6-12 months
Changes in the PGC1α-Sirt1 axis from baseline to 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.
Time frame: Baseline 6-12 months
Changes in cellular metabolism from baseline to 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.
Time frame: Baseline 6-12 months