Canakinumab for the treatment of postprandial hypoglycaemia: study protocol for a randomised, placebo-controlled, parallel-group, double-blind, multicentric, superiority trial-the CanpHy study.

Abstract

Introduction Postbariatric hypoglycaemia (PBH) is a complex medical condition with a significant impact on patients' quality of life. The underlying mechanisms remain to be elucidated. We have shown that food ingestion increases IL-1β and subsequently stimulates insulin secretion. We therefore hypothesised that overactivation of the IL-1β pathway could lead to PBH by promoting excessive insulin secretion after a meal. In a proof-of-concept study, we have shown that acute treatment with the IL-1 receptor antagonist anakinra can attenuate PBH after a single liquid mixed meal. This study aims to validate this therapeutic approach over a longer period of time using the long-acting anti-IL-1β antibody canakinumab. Methods And Analysis In this prospective, randomised, double-blind, placebo-controlled, multicentre trial, we plan to enrol 62 adult patients after bariatric surgery with frequent, postprandial hypoglycaemia (ie, <3.0 mmol/L and at least five hypoglycaemic episodes per week). Eligible subjects will be randomised to receive either single-dose 150 mg canakinumab (Ilaris, Novartis) subcutaneously (s.c.) or matched placebo (1.0 mL physiologic saline). For 28 days, patients are required to wear a blinded continuous glucose monitoring device (CGMS, Dexcom G6) and use a diary to track their hypoglycaemic episodes. Primary outcomes include health-related quality of life, measured by the SF-36, as well as postprandial hypoglycaemic events (glucose <3.0 mmol/L). A significant improvement in any one of these outcomes will be considered sufficient to demonstrate the clinical superiority of canakinumab over placebo. Secondary outcomes include patient-oriented measures such as postprandial hypoglycaemic symptoms, hypoglycaemia unawareness, fear of hypoglycaemia, as well as metabolic measures and safety assessments. Ethics And Dissemination The trial was approved by the Cantonal Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' in January 2022 (#2021-02325), as well as by Swissmedic in April 2022 (#701280). Current, approved protocol version 1.3 of 28.03.2023. The study is actively recruiting. Results will be published in a relevant scientific journal and communicated to participants and relevant institutions through dissemination activities. Individual data are accessible on request. Trial Registration The study is registered with the www. Clinicaltrials gov registry (NCT05401578) and the Swiss National Clinical Trials Portal (SNCTP) on www.kofam.ch (SNCTP000004838).