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

NCT02055014 | Unknown Phase 4 DMC

• 3 other identifiers: 12DIAB15ISRCTN001510532012-004988-42
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 4

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.

Conditions

Type 2 Diabetes; Obesity; Diabesity

Keywords

Endobarrier; Duodenal-jejunal bypass liner; Glucagon-like peptide-1 receptor agonist; Liraglutide; Diabesity; Type 2 diabetes; Obesity

Outcome Measures

Primary Outcomes (1)

• Glycated haemoglobin (HbA1c)

  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.

  24 months

Secondary Outcomes (1)

• Weight

  24 months

Study Arms (3)

Liraglutide alone

ACTIVE COMPARATOR

Liraglutide 1.8mg once daily subcutaneous injection

Drug: Liraglutide

Endobarrier alone

EXPERIMENTAL

Duodenal-jejunal bypass liner (Endobarrier) device implantation without additional GLP-1RA therapy

Device: Duodenal-jejunal bypass liner - Endobarrier device

Endobarrier and Liraglutide

EXPERIMENTAL

Duodenal-jejunal bypass liner (Endobarrier) device with combined liraglutide 1.2mg once daily subcutaneous injection

Drug: Liraglutide; Device: Duodenal-jejunal bypass liner - Endobarrier device

Interventions

Liraglutide DRUG

Also known as: Victoza

Endobarrier and Liraglutide; Liraglutide alone

Duodenal-jejunal bypass liner - Endobarrier device DEVICE

Also known as: EC Certificate Full Quality Assurance System: Certificate US08/5323

Endobarrier alone; Endobarrier and Liraglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• \<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)

Sponsors & Collaborators

• Sandwell & West Birmingham Hospitals NHS Trust: lead
• Association of British Clinical Diabetologists: collaborator

Study Sites (4)

Department of Diabetes, City Hospital

Birmingham, B18 7QH, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, G0, United Kingdom

Location

Department of Diabetes, Guy's and St Thomas' Hospitals

London, SE1, United Kingdom

Location

Diabetes Research Group, King's College London

London, SE5 9RS, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Diabesity

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Complications

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Bob Ryder, MD FRCP

  Sandwell and West Birmingham Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator, Consultant Physician (Diabetes)

Study Record Dates

• First Submitted: February 3, 2014
• First Posted: February 4, 2014
• Study Start: July 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: April 26, 2016

Record last verified: 2016-04

Locations

GB (4)