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CLINICAL RESEARCH CASE STUDY Video Camera Endoscopy (VCE) Clinical Trials How to asset the ability of the probiotic strain to attenuate NSAIDs effect in deterioration of small intestinal mucosa tissue
Presented by:
Video Camera Endoscopy (VCE) Clinical Trials
Executive Summary
Non-Steroidal Drugs (NSAIDs) are commonly used worldwide, both as prescription-only medicines and as “over-the-counter” preparations. However, low dose use of NSAIDS, is associated with gastrointestinal (GI) injury. Strategies to prevent GI complications associated with NSAID use included are generally associated with undesired side effects, whereas live bacteria formulated as probiotics may offer a safe alternative to prevent or at least decrease negative side effects of NSAIDS such as Aspirin. The present clinical trial is aiming to bring a product containing a probiotic strain able to attenuate and/or reverse Aspirin-induced small intestinal damage and GI symptoms in Aspirin users. Challenges and Objectives Anti-Inflammatory
We established a clinical challenge model aiming at investigating the ability of the probiotic strain in attenuating and/or reversing deterioration in the healthy human gastrointestinal tract
The Sponsor needed a highly experienced research partner able to assess the deterioration of small intestinal mucosa tissue however they needed a method not too invasive in order to overcome the Ethical burdens. The main objectives were: • To investigate the ability of the probiotic strain to attenuate and/or reverse low-dose, long-term Aspirin-induced deterioration of small intestinal mucosa tissue as assessed by capsule endoscopy in healthy volunteers • To investigate the ability of the probiotic strain to attenuate and reverse low-dose, long termAspirin-induced GI symptoms as assessed AUC ulcer number as well as assessed by AUC of pain syndrome score for GSRS. • To investigate co-administration of the probiotic strain to low-dose, long term Aspirin on changes in multiple biomarkers of general intestinal barrier function in blood and faecal samples. How Atlantia’s Solution Helped Consequently, we established a clinical challenge model aiming at investigating the ability of the probiotic strain in attenuating and/or reversing deterioration in the healthy human gastrointestinal tract. Thedeteriorationwas inducedby a chemical agent commonlyusedand with well-established deteriorating effects on the small intestine. For the primary endpoint, we used the method capsule endoscopy (CE) to assess the small intestinal damage. Capsule endoscopy has been reviewed in a technology status evaluation report by the American society for gastrointestinal endoscopy and it is now the gold standard for assessing occult gastrointestinal bleeding, and indications for its use are continuing to expand. Current uses include exploration and surveillance of bowel pathology such as in Crohn’s disease, polyps, small bowel malignancy and drug-induced mucosal injury. Capsule endoscopy (CE) is generally a safe and well tolerated procedure. Atlantia has a highly expert team on managing these technologies when conducting trials and was a perfect fit for the sponsor.
atlantiaclinicaltrials.com
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Video Camera Endoscopy (VCE) Clinical Trials
About the Study This trial was a single-site, randomised, double-blind, placebo-controlled, two-armed, parallel-group trial in healthy, adult volunteers. It investigated the effect of daily intake of the probiotic strain or placebo when co-administered with daily intake of 300mg of Aspirin.
DESIGN
The trial was conducted in accordance with the ethical principles set forth in the current version of the Declaration of Helsinki (seventh revision; October 2013), the International Conference on Harmonization E6 Good Clinical Practice (ICH-GCP, 10 June 1996) and all applicable local regulatory requirements. The trial included a run-in period of two weeks duration followed by a six-week intervention period where the probiotic/placebo and Aspirin were co-administered. After the 6-weeks, the probiotic/placebo was given for two additional weeks to investigate the potential effects of the probiotic on intestinal healing after long-time Aspirin use. Subjects participated in the trial for a total duration of 10-weeks including the run-in phase. The trial consisted of 6 visits following screening. The primary efficacy variable was to investigate the effect of 8-weeks oral supplement of the probiotic strain versus placebo on small intestinal mucosa damage when co-administered with an Aspirin challenge for 6-weeks measured as the area-under-the-curve (AUC) for Lewis Score obtained by capsule endoscopy. The sample size of 30 completing participants in each arm was estimated based on a power calculation performed on intervention on percent difference of AUC between two normalized curves (active vs. placebo) as an approximation. To account for a potential drop-out rate of approximately 15%, a total of 35 subjects were randomized in each group. A decrease of 30% in the AUC following treatment of the probiotic compared to placebo was considered to be clinically relevant and detected as significant.
ETHICS
RECRUITMENT
CONDUCT
ANALYSIS
REPORTING
Throughout the entire trial, subjects were instructed to maintain their habitual life style with regard to diet, physical activity level and sleep habits. Intake of probiotic products aswell as food and food supplements containing probiotics were not allowed from the screening visit and until the end of the intervention period. Subjects were not withdrawn from the trial due to single violations, but violations were recorded as protocol deviations. Small intestine mucosa deterioration was evaluated using capsule endoscopy as well as indirect biomarkers in feaces and blood samples At these visits, subjects also filled out the GSRS questionnaire which assessed GI symptoms and pain. Each subject underwent video capsule endoscopy after 1-week and 4-weeks of taking aspirin and omeprazole, along with either investigational product or placebo therapy. The primary endpoint was to evaluate small bowel damage in healthy subjects before and after taking low-dose aspirin for 4-week16. Capsule endoscopy was deemed to be a relevant and acceptable method to evaluate both mild and severe intestinal damage caused by low dosage of Aspirin measured as area-under-the-curve for damage observed by capsule endoscopy over the 8 week trial intervention period.
atlantiaclinicaltrials.com
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CLINICAL RESEARCH CASE STUDY Video Camera Endoscopy (VCE) Clinical Trials How to asset the ability of the probiotic strain to attenuate NSAIDs effect in deterioration of small intestinal mucosa tissue
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