Randomisation to Endobarrier Alone Versus With Incretin Analogue in SustainEd Diabesity (REVISE-Diabesity)

Phase 4

• Conditions: Obesity; Type 2 Diabetes; Diabesity
• Interventions: Device: Duodenal-jejunal bypass liner - Endobarrier device; Drug: Liraglutide

• Registration Number: NCT02055014
• Lead Sponsor: Sandwell & West Birmingham Hospitals NHS Trust

Brief Summary

New effective non-surgical treatments are needed for patients whose obesity and type 2 diabetes (T2DM) do not respond to current medical therapies. We propose a randomised controlled trial of Endobarrier, an implantable intestinal device that separates ingested food from contacting the first 60cm of intestine where sited and that mimics some of the clinical effects of bariatric surgery (improved metabolic control with weight loss) with or without continued use of the GLP-1 receptor agonist (GLP-1RA) Liraglutide 1.2mg vs Liraglutide 1.8mg without the device in obese patients with T2DM who remain with suboptimal glycaemic control despite current conventional diabetes treatment, in an NHS setting.

Seventy-two patients with T2DM and obesity (HbA1c≥7.5%, BMI≥35kg/m2) despite previous GLP-1RA therapy will be studied over 24 months and randomised to receive Endobarrier with continued Liraglutide 1.2mg for 12 months; Endobarrier alone for 12 months; or Liraglutide 1.8mg without Endobarrier.

We will investigate potential mechanisms of action and their time course as part of the study by repeated measures of: 1. insulin resistance measures, gut peptides, bile acids; 2. energy intake and nutritional composition; 3. liver fat stores, 4. intestinal inflammation and permeability measures.

The data will inform clinical use of the device and development of new treatments for T2DM and obesity.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07
• Study First Submitted: 2014-02-03
• Study First Submitted QC: 2014-02-03
• Study First Posted: 2014-02-04
• Status Verified: 2016-04
• Last Update Submitted: 2016-04-25
• Last Update Posted: 2016-04-26
• Primary Completion: 2017-03
• Study Completion: 2017-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

• type 2 diabetes with latest HbA1c ≥7.5% (≥58mmol/mol)
• obesity with latest BMI ≥35 Kg/m2 (≥30 Kg/m2 for those of South Asian origin)
• liraglutide therapy for at least 6 months - HbA1c and weight trend data should be available
• stable weight and HbA1c in preceding 3 months (<3 Kg reduction in weight and <0.3% reduction in HbA1c)

Exclusion Criteria

• <18 years of age
• abnormal intestinal anatomy e.g. Crohn's disease
• contraindication to oesophago-gastroduodenoscopy
• previous bariatric surgery or bowel surgery
• active infection
• anticoagulation therapy which cannot be discontinued/ coagulopathy INR >1.3
• eGFR <30
• known portal hypertension
• previous pancreatitis or amylase > 3 times the upper limit of normal
• uncontrolled cardiovascular disease
• lactating or pregnant females
• patients taking aspirin in whom it should continue (e.g. active ischaemic heart disease or cerebrovascular disease)
• excess anaesthetic risk as identified by the anaesthetist or investigator (e.g. uncontrolled obstructive sleep apnoea)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Endobarrier alone	Duodenal-jejunal bypass liner - Endobarrier device	Duodenal-jejunal bypass liner (Endobarrier) device implantation without additional GLP-1RA therapy
Endobarrier and Liraglutide	Duodenal-jejunal bypass liner - Endobarrier device	Duodenal-jejunal bypass liner (Endobarrier) device with combined liraglutide 1.2mg once daily subcutaneous injection
Liraglutide alone	Liraglutide	Liraglutide 1.8mg once daily subcutaneous injection
Endobarrier and Liraglutide	Liraglutide	Duodenal-jejunal bypass liner (Endobarrier) device with combined liraglutide 1.2mg once daily subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Glycated haemoglobin (HbA1c)	24 months	HbA1c (mmol/mol; %) at end of follow-up period compared to baseline. This will be 12 months following Endobarrier device removal which will usually be 24 months after initial the device has first been implanted (for 12 months) or 24 months from Liraglutide 1.8mg initiation.

Secondary Outcome Measures

Name	Time	Method
Weight	24 months	Weight (Kg) measured at end of follow-up period compared to baseline. This will be 12 months following Endobarrier device removal which will usually be 24 months after the device has first been implanted (for 12 months) or 24 months from Liraglutide 1.8mg initiation.

Trial Locations

Locations (4)

Department of Diabetes, Guy's and St Thomas' Hospitals; 🇬🇧 London, United Kingdom

Glasgow Royal Infirmary; 🇬🇧 Glasgow, United Kingdom

Department of Diabetes, City Hospital; 🇬🇧 Birmingham, United Kingdom

Diabetes Research Group, King's College London; 🇬🇧 London, United Kingdom