REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)

NCT ID: NCT01483560

Last Updated: 2019-06-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

493 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-31

Study Completion Date

2017-04-18

Brief Summary

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The trial is conducted in the United Kingdom (UK), Australia, Canada, Denmark and the Netherlands. The aim is to test whether 3 years treatment with metformin added to titrated insulin therapy (towards target HbA1c 7.0%/53 mmol/mol) reduces atherosclerosis, as measured by progression of carotid intima-media thickness (cIMT), in adults with confirmed type 1 diabetes aged 40 years and over at increased risk for cardiovascular disease.

Detailed Description

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Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Metformin

Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

3 years treatment duration

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

3 years duration

Interventions

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Metformin

3 years treatment duration

Intervention Type DRUG

Placebo

3 years duration

Intervention Type DRUG

Other Intervention Names

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Glucophage

Eligibility Criteria

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Inclusion Criteria

* Type 1 Diabetes for five years or more\*
* Age 40 years or above
* 7.0 =\< HbA1c \<10.0% (53 - 86 mmol/mol)

AND 3 or more of the following ten CardioVascular Disease (CVD) risk factors:

* BMI \>27 kg/m\^2
* Current HbA1c \>8.0% (64 mmol/mol)
* Known CVD/peripheral vascular disease
* Current smoker
* Estimated glomerular filtration rate (eGFR) \<90 ml/min per 1.73 m\^3
* Confirmed micro- or macroalbuminuria \[according to local assays and reference ranges\]
* Hypertension (BP \>=140/90 millimeters of mercury (mmHg) or established on antihypertensive treatment)
* Dyslipidaemia \[total cholesterol \>=5.0 mmol/L (200 mg/dL);OR HDL cholesterol \<1.20 mmol/L (46mg/dL) \[MEN\]; OR \<1.30 mmol/L (50 mg/dL) \[WOMEN\]; or triglycerides \>=1.7 mmol/L (150mg/dL); or established on lipid-lowering treatment)\]
* Strong family history of CVD (at least one parent, biological aunt/ uncle, or sibling with myocardial infarction or stroke aged \<60 years)
* Duration of diabetes \> 20 years

Exclusion Criteria

* eGFR \< 45 ml/min/1.73m2
* woman of childbearing age not on effective contraception
* Pregnancy and/or lactation
* Acute coronary syndrome or Stroke/Transient Ischaemic Attack within the last three months
* NYHA stage 3 or 4 heart failure
* Significant hypoglycaemia unawareness
* Impaired cognitive function/ unable to give informed consent
* Previous carotid surgery/ inability to capture adequate carotid images
* Estimated glomerular filtration \< 45ml/min/1.73m\^2 (MDRD)
* Gastroparesis
* History of lactic acidosis
* Other contraindications to metformin (hepatic impairment, known hypersensitivity to metformin, acute illness such as dehydration, severe infection, shock, acute cardiac failure or suspected tissue hypoxia)
* Any coexistent life threatening condition including prior diagnosis of cancer within two years
* History of alcohol problem or drug abuse
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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NHS Greater Glasgow and Clyde

OTHER

Sponsor Role collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role collaborator

Imperial College London

OTHER

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role collaborator

University of Dundee

OTHER

Sponsor Role collaborator

Merck Serono S.A., Geneva

INDUSTRY

Sponsor Role collaborator

Itamar-Medical, Israel

INDUSTRY

Sponsor Role collaborator

University of Western Ontario, Canada

OTHER

Sponsor Role collaborator

University of Melbourne

OTHER

Sponsor Role collaborator

Steno Diabetes Center Copenhagen

OTHER

Sponsor Role collaborator

Maastricht University Medical Center

OTHER

Sponsor Role collaborator

University of Glasgow

OTHER

Sponsor Role lead

Responsible Party

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Prof John Petrie

Clinical Professor in Diabetic Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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John Petrie, Prof

Role: PRINCIPAL_INVESTIGATOR

University of Glasgow

Helen Colhoun, Prof

Role: STUDY_DIRECTOR

University of Dundee

Locations

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Royal Melbourne Hospital

Melbourne, , Australia

Site Status

St Vincent's Hospital

Melbourne, , Australia

Site Status

Royal Prince Albert Hospital

Sydney, , Australia

Site Status

St Joseph's Health Care

London, Ontario, Canada

Site Status

Ottawa Hospital Riverside Campus

Ottawa, , Canada

Site Status

Steno Diabetes Centre

Gentofte Municipality, , Denmark

Site Status

Maastricht University Medical Centre

Maastricht, , Netherlands

Site Status

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

Ayr Hospital

Ayr, , United Kingdom

Site Status

University Hospitals Bristol

Bristol, , United Kingdom

Site Status

Diabetes Support Unit, Ninewells Hospital and Medical School

Dundee, , United Kingdom

Site Status

University Hospital North Durham

Durham, , United Kingdom

Site Status

Edinburgh Royal Infirmary

Edinburgh, , United Kingdom

Site Status

Edinburgh Western Infirmary

Edinburgh, , United Kingdom

Site Status

Peninsula NIHR Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust

Exeter, , United Kingdom

Site Status

Stobhill Hospital, Diabetes Clinic

Glasgow, , United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, , United Kingdom

Site Status

Michael White Diabetes Centre, Hull Royal Infirmary

Hull, , United Kingdom

Site Status

Clinical Sciences Centre, University Hospital

Liverpool, , United Kingdom

Site Status

Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status

Wellcome Trust Clinical Research Facility, Manchester Royal Infirmary

Manchester, , United Kingdom

Site Status

Newcastle NIHR Clinical Research Facility, Royal Victoria Hospital

Newcastle, , United Kingdom

Site Status

Diabetes Clinical Research Centre, Plymouth

Plymouth, , United Kingdom

Site Status

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Site Status

Countries

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Australia Canada Denmark Netherlands United Kingdom

References

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El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.

Reference Type DERIVED
PMID: 38837240 (View on PubMed)

Petrie JR, Chaturvedi N, Ford I, Brouwers MCGJ, Greenlaw N, Tillin T, Hramiak I, Hughes AD, Jenkins AJ, Klein BEK, Klein R, Ooi TC, Rossing P, Stehouwer CDA, Sattar N, Colhoun HM; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Aug;5(8):597-609. doi: 10.1016/S2213-8587(17)30194-8. Epub 2017 Jun 11.

Reference Type DERIVED
PMID: 28615149 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2011-000300-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GN10DI406

Identifier Type: -

Identifier Source: org_study_id

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