LIMIT-1: Lowering the Incidence of vascular complications with Metformin in patients with Impaired glucose Tolerance and a recent transient ischaemic attack or minor ischaemic stroke: a phase II randomised, controlled trial

ISRCTN	ISRCTN54960762
DOI	https://doi.org/10.1186/ISRCTN54960762
Protocol serial number	N/A
Sponsor	Erasmus Medical Centre (The Netherlands)
Funder	Erasmus Medical Centre (The Netherlands)

Submission date: 11/04/2007
Registration date: 11/04/2007
Last edited: 20/03/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Ms Esther van der Heijden
Scientific

Stroke Research Assistant
Erasmus Medical Centre
Room Ee 22.42
P.O. Box 1738
Rotterdam
3000 DR
Netherlands

Phone	+31 (0)10 408 7818
Email	stroke-research@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Randomised, open-label, multicentre, controlled, parallel group trial
Secondary study design	Non randomised controlled trial
Scientific title
Study acronym	LIMIT-1
Study objectives	Metformin will be tolerated in patients with Transient Ischaemic Attack (TIA) or minor ischaemic stroke and will result in blood glucose lowering.
Ethics approval(s)	Received from the Medical Ethics Committee of Erasmus Medical Centre on the 5th December 2006 (ref: NL15011.078.06 [local METC number MEC-2006-303]).
Health condition(s) or problem(s) studied	Transient ischaemic attack or minor ischaemic stroke
Intervention	Patients will be randomised for metformin or no oral anti-diabetic drug (open-label) on top of optimal standard treatment, including lifestyle advice aimed at weight reduction and regular physical exercise. Patients allocated to metformin will be treated with metformin for three months from the day of randomisation until study end. They will start with a daily dose of 500 mg that will be slowly increased in one-month time to a daily dose of 2,000 mg in two gifts. All patients will be followed for three months.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Metformin
Primary outcome measure(s)	1. Tolerability of metformin treatment (measured as number of patients still on treatment after three months) 2. The safety of metformin treatment (which will be continuously monitored) 3. The adjusted difference in two-hour post-load glucose levels at three months Primary outcomes will be measured at three months for feasability (safety will be continuously monitored). Primary outcome on effect on post-load glucose level will be measured at three months, expressed as a for baseline adjusted difference in mean two-hour post-load glucose levels at three months between treatment groups.
Key secondary outcome measure(s)	1. Differences in fasting glucose levels 2. Insulin resistance 3. Body mass index 4. Percentage of patients with a normal glucose tolerance at three months Secondary outcomes will be measured at three months, as a for baseline adjusted difference between groups.
Completion date	01/02/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	40
Key inclusion criteria	1. Men or women 18 years and over 2. TIA/minor ischaemic stroke (modified Rankin Score three or less) within six months 3. Impaired fasting glucose (fasting glucose level of 5.6 to 6.9 mmol/L) and/or impaired glucose tolerance (two-hour post-load glucose level of 7.8 to 11.0 mmol/L) 4. Informed consent
Key exclusion criteria	1. Known or newly diagnosed diabetes mellitus 2. Contraindication for metformin: 2.1. Renal impairment (serum creatinine greater than 135 micromol/L for men, and greater than 110 micromol/L for women) 2.2. Hepatic disease (liver enzymes increased twice the upper limit of normal) 2.3. A past history of lactic acidosis 2.4. Cardiac failure requiring pharmacological therapy 2.5. Chronic hypoxic lung disease 2.6. Pregnancy 2.7. Breast feeding 3. Severe comorbidity interfering with follow-up
Date of first enrolment	01/02/2007
Date of final enrolment	01/02/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

Stroke Research Assistant

Rotterdam
3000 DR
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan