Clinical Trials Register

Summary
EudraCT Number:	2012-004988-42
Sponsor's Protocol Code Number:	12DIAB15
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2013-01-04
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2012-004988-42

A.3

Full title of the trial

REVISE-Diabesity: Randomisation to Endoluminal intestinal liner alone Versus with Incretin analogue in SustainEd Diabesity

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical trial of patients with type 2 diabetes and obesity randomly allocated to be implanted with an intestinal liner device with or without standard diabetes liraglutide medical therapy or liraglutide alone.

A.3.2

Name or abbreviated title of the trial where available

REVISE-Diabesity

A.4.1

Sponsor's protocol code number

12DIAB15

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sandwell and West Birmingham Hospitals NHS Trust
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Association of British Clinical Diabetologists
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	City Hospital, Birmingham
B.5.2	Functional name of contact point	Dr Bob Ryder
B.5.3	Address:
B.5.3.1	Street Address	Department of Diabetes, Dudley Road
B.5.3.2	Town/ city	Birmingham
B.5.3.3	Post code	B18 7QH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01215074191
B.5.6	E-mail	bob.ryder@nhs.net

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Victoza
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Liraglutide
D.3.2	Product code	n/a
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Liraglutide
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Combined Type 2 diabetes mellitus and obesity.

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes, a disorder of insulin resistance resulting associated with high glucose 'sugar' levels with associated short and long-term complications; Obesity.

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10063624
E.1.2	Term	Type II diabetes mellitus inadequate control
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10029883
E.1.2	Term	Obesity
E.1.2	System Organ Class	10027433 - Metabolism and nutrition disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

In an NHS setting, what is the impact of Endobarrier (a device inserted into the intestine to coat its inside and prevent absorption of food where it is sited) alone versus combined Endobarrier-Liraglutide therapy (a daily injectable medication for type 2 diabetes) in patients with obesity and type 2 diabetes mellitus who have not yet met national treatment targets despite at least 6 months of Liraglutide treatment alone?

E.2.2

Secondary objectives of the trial

What are the mechanisms of action by which Endobarrier exerts its effect of weight reduction and improved diabetes control?

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients will be eligible to be included in this randomised clinical trial if they meet the following inclusion criteria: 1. participation in ABCD Nationwide Liraglutide Audit with data for at least 6 months, 2. HbA1c ≥7.5% after at least 6 months’ Liraglutide treatment, 3. BMI ≥35 Kg/m2 (≥30 Kg/m2 for Asian origin patients), 4. stable weight and HbA1c in preceding 3 months (<3 Kg reduction in weight and <0.3% reduction in HbA1c).

E.4

Principal exclusion criteria

Exclusion criteria will include the following: abnormal intestinal anatomy; contraindication to oesophago-gastroduoenoscopy; previous bariatric surgery or bowel surgery; active infection or CRP >10; anticoagulation therapy; 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 with active ischaemic heart disease or cerebrovascular disease or those in whom aspirin treatment should continue. Patients taking regular aspirin will need to discontinue it for the duration of the Endobarrier implantation if randomised to that arm and so for those in whom it is taken for primary prevention, the potential risks and benefits of deciding to discontinue aspirin will be weighed up by the clinician concerned in consultation with the patient.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome measure for the study will be participant weight and HbA1c in the two Endobarrier-treated groups at the last follow-up visit, which will be at 12 months after Endobarrier removal (equivalent to 12 months after Endobarrier implantation).

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months post-explant of the Endobarrier device, which will usually be inserted for 1 year. Therefore 24 months from implant of the Endobarrier.

E.5.2

Secondary end point(s)

The secondary end points are: fasting insulin, glucose, c-peptide to calculate HOMA-IR and bile acids; hepatic and pancreatic triacylglycerol stores; quality of life scores; gut microbiota and faecal calprotectin changes over time in Endobarrier-treated patients.

E.5.2.1

Timepoint(s) of evaluation of this end point

Insulin resistance (HOMA-IR) to be evaluated at days 2, 4 and 7 post Endobarrier placement and days 2,4 and 7 post Endobarrier removal and compared to baseline. Hepatic and pancreatic triacylglycerol stores compared at 3 months post Endobarrier placement to baseline.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Endobarrier device

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1