A Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of (Thetanix) <i>Bacteroides thetaiotaomicron</i> in Adolescent Crohn's Disease



Hansen, Richard, Sanderson, Ian R, Muhammed, Rafeeq, Allen, Stephen ORCID: 0000-0001-6675-249X, Tzivinikos, Christos, Henderson, Paul, Gervais, Lisa, Jeffery, Ian B, Mullins, David P, O'Herlihy, Eileen A
et al (show 4 more authors) (2021) A Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of (Thetanix) <i>Bacteroides thetaiotaomicron</i> in Adolescent Crohn's Disease. CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY, 12 (1). e00287-.

[img] PDF
A Double-Blind, Placebo-Controlled Trial to Assess Safety and Tolerability of (Thetanix) Bacteroides thetaiotaomicron in Ado.pdf - Other

Download (398kB) | Preview

Abstract

<h4>Introduction</h4>Thetanix (gastroresistant capsules containing lyophilized Bacteroides thetaiotaomicron) is a live biotherapeutic, under development for Crohn's disease, that antagonizes transcription factor nuclear factor kappa B, reducing proinflammatory cytokines, particularly tumor necrosis factor alpha. We aimed to assess safety and tolerability in adolescents with Crohn's disease in remission.<h4>Methods</h4>Subjects who were 16-18 years with Crohn's in remission (weighted pediatric Crohn's disease activity index <12.5) were recruited. Each active dose comprised ∼108.2±1.4 colony forming units of B. thetaiotaomicron (randomized 4:1 active:placebo). Part A was single dose. Part B involved 7.5 days twice daily dosing. Serial stools were analyzed for calprotectin, 16S rRNA sequencing, and B. thetaiotaomicron real-time polymerase chain reaction. Bloods were taken serially. Subjects reported adverse events and recorded temperature twice daily.<h4>Results</h4>Fifteen subjects were treated-8 in part A (75% men, median 17.1 years) and 10 in part B, including 3 from part A (80% men, median 17.1 years); all 18 completed. Seventy percent took concurrent immunosuppression. Reported compliance was >99% in part B. Two subjects reported adverse events deemed related-one in part A with eructation, flatulence, and reflux; one in part B with dizziness, abdominal pain, and headache. No serious adverse events were reported. There was no significant change in median calprotectin across part B (87.8 [4.4-447] to 50.5 [5.3-572], P = 0.44 by the Fisher exact test in the active group). No significant differences were found in microbiota profiles, but diversity seemed to increase in treated subjects.<h4>Discussion</h4>Thetanix, after single and multiple doses, was well tolerated. Although the numbers in this study were small, the safety profile seems good. Future studies should explore efficacy.

Item Type: Article
Uncontrolled Keywords: Humans, Crohn Disease, DNA, Bacterial, RNA, Ribosomal, 16S, Placebos, Freeze Drying, Treatment Outcome, Biological Therapy, Remission Induction, Follow-Up Studies, Double-Blind Method, Adolescent, Female, Male, Gastrointestinal Microbiome, Bacteroides thetaiotaomicron
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Faculty Management Office
Depositing User: Symplectic Admin
Date Deposited: 23 Dec 2022 08:28
Last Modified: 17 Oct 2023 21:29
DOI: 10.14309/ctg.0000000000000287
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3166762