Clinical Trials Register

Summary
EudraCT Number:	2011-003572-36
Sponsor's Protocol Code Number:
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2011-12-06
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

2011-003572-36

A.3

Full title of the trial

The role of GLP-1 analogues in reducing reperfusion injury after acute stroke in patients with impaired swallowing.

A.3.1

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

The role of gut hormones replacement in improving blood flow to the brain after stroke that affects swallowing.

A.3.2

Name or abbreviated title of the trial where available

Liraglutide after Acute Stroke Trial (LAST).

A.4.1

Sponsor's protocol code number

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	Royal Devon & Exeter NHS Foundation 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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Diabetes & Vascular Research Centre
B.5.2	Functional name of contact point	David Strain
B.5.3	Address:
B.5.3.1	Street Address	Peninsula College of Medicine & Dentistry, Barrack Road
B.5.3.2	Town/ city	Exeter
B.5.3.3	Post code	EX2 5DW
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01392403017
B.5.6	E-mail	david.strain@pms.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	University of Exeter
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	University of Exeter
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	Diabetes & Vascular Research Centre, Peninsula College of Medicine & Dentistry
B.5.2	Functional name of contact point	Dr. David Strain
B.5.3	Address:
B.5.3.1	Street Address	Barrack Road
B.5.3.2	Town/ city	Exeter
B.5.3.3	Post code	Ex2 5AX
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	01392403058
B.5.5	Fax number	01392403027
B.5.6	E-mail	david.strain@pms.ac.uk

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	Liraglutide
D.2.1.1.2	Name of the Marketing Authorisation holder	Novo Nordisk
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	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.3.11 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

We plan to give a synthetic form of GLP-1 (Liraglutide) that is already available and licensed for use in patients with diabetes in the UK, to patients who have had an acute stroke, in order to determine whether increased levels protect the brain during its recovery, resulting in better recovery.

E.1.1.1

Medical condition in easily understood language

Investigating the effect of GLP-1 analogues (Liraglutide) to protect the brain during its recovery from an acute stroke.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
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

This is a pilot study to inform and guide the processes needed for a larger multicentre trial, to estimate the cost and to prepare for an HTA/NIHR grant application. GLP-1 (Glucagon like peptide) is a gut hormone that is known to regulate blood flow in vessels and prevents cell-death. After a stroke, patients are often placed "Nil by Mouth" due to concerns over swallowing safely. This will reduce the levels of GLP-1. We wish to replace this GLP-1 using the preparation widely used for the treatment of Diabetes to determine if this benefits the blood supply to the brain and preservation of healthy brain. This pilot study will guide the processes required to organise the definitive study to determine the benefit of liraglutide after a stroke on clinical outcomes. Study Objectives: 1-To recruit 40 consecutive stroke patients presenting within 6 hours who are put nil by mouth. 2-To record basic data on patients who were eligible for recruitment but were not recruited..

E.2.2

Secondary objectives of the trial

Our secondary objective: 1- To record MRI volumetric infarction size after 1 week of treatment with liraglutide in addition to usual care vs. 1 week of standard care only. 2- To assess the benefit to clinical outcome after a stroke using the NIHSS scoring system (at 1 week and a 1 month) after 7 days of treatment with liraglutide, compared to usual care only. 3- To explore the effects of liraglutide treatment on systemic microvascular function and vascular autoregulation after an acute stroke and its impact on recovery from stroke. To assess the feasibilty of performing those microvascular assessments in a large multi centre trial.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients over the age of 18 years, presenting within 6 hours of an acute stroke who are able to consent or have next of kins who can provide assent and are planned to be placed nil by mouth for at least 12 hours.

E.4

Principal exclusion criteria

Inability to provide informed consent or inability to contact a relative or carer who can provide assent. Stroke as a result of an intra-cerebral bleed. Pregnancy and breast feeding. Liver impairment, Type I diabetes, Patients who are on insulin, Sulphonylurea therapy or other GLP-1 treatment, Hypersensitivity to Liraglutide Other contraindication for the use of Liraglutide (as per SmPC).

E.5 End points

E.5.1

Primary end point(s)

To pilot the processes required to organise a definitive study to determine the benefit of liraglutide after a stroke on clinical outcomes. As part of this aim we will assess the feasibility of the study, for example, rate of participant recruitment, cost of running the study and the practicalities of performing the microvascular assessments in an acute setting

E.5.1.1

Timepoint(s) of evaluation of this end point

NIHSS score(National Institute of Health Stroke Scale)will be assessed at admission and at 1 week and 1 month after stroke as a measure of clinical outcome.

E.5.2

Secondary end point(s)

i) To compare the brain infarction size using MRI volumetric measurements after 1 week of treatment with Liraglutide in addition to usual care vs. 1 week of standard care only. ii) To assess the benefit to clinical outcome after a stroke using the NIHSS scoring system (at 1 week and 1 month) after 7 days of treatment with Liraglutide, compared to usual care only. iii) To assess the effect of Liraglutide treatment on microvascular function to determine whether improvement in microvascular function have detrimental effect on clinical outcome.

E.5.2.1

Timepoint(s) of evaluation of this end point

It is anticipated this study will recruit on average only one patient every 2 weeks. It is estimated therefore that the first interim analysis (12 patients) will take place after six months.

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

standard medical care

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

The end of study will be defined as the collection of last data set (whether it is NIHSS, MRI or unfeasibility of collection of data set for any reason).

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