Nicotinamide Riboside in Ulcerative Colitis

Обзор

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

Подробное описание

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.

Вмешательства

• Пищевая добавка Nicotinamide Riboside Chloride
  The intervention consists of 6 months to 1 year of daily oral therapy with Nicotinamide Riboside Chloride (Niagen) in addition to standard therapy.
• Пищевая добавка Placebo
  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.
• Другое Standard of Care
  Standard of Care

Первичные конечные точки

• Number of patients screened [Срок оценки: 2 years]
• Proportion of patients screened who meet inclusion/exclusion criteria [Срок оценки: 2 years]
• Enrollment percentage [Срок оценки: 2 years]
• Completion percentage [Срок оценки: 2 years]
• Reasons for exclusion [Срок оценки: 2 years]
• Dropout rate [Срок оценки: 2 years]
• Reasons for dropout [Срок оценки: 2 years]

Вторичные конечные точки (4)

• Changes in mitochondrial structure from baseline to 6-12 months [Срок оценки: Baseline 6-12 months]
• Changes in mitochondrial function from baseline to 6-12 months [Срок оценки: Baseline 6-12 months]
• Changes in the PGC1α-Sirt1 axis from baseline to 6-12 months [Срок оценки: Baseline 6-12 months]
• Changes in cellular metabolism from baseline to 6-12 months [Срок оценки: Baseline 6-12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Поддерживающая терапия

Центры проведения

США · 1 центр

• UPMC Children's Hospital of Pittsburgh — Pittsburgh

Публикации

• 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. PMID 26484345
• 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. PMID 26969166
• 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, PMID 30604764
• 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. PMID 26912654
• 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. PMID 26788256
• 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. PMID 28877980
• 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. PMID 32486488
• 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. PMID 27721479

Идентификаторы

NCT: NCT05561738 · STUDY22060104

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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