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Trial record 1 of 1 for:    Reducing with Metformin Vascular Adverse Lesions
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REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL) (REMOVAL)

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ClinicalTrials.gov Identifier: NCT01483560
Recruitment Status : Completed
First Posted : December 1, 2011
Last Update Posted : April 27, 2017
NHS Greater Glasgow and Clyde
Juvenile Diabetes Research Foundation
Imperial College London
University of Wisconsin, Madison
University of Dundee
Merck Serono S.A., Geneva
Itamar-Medical, Israel
University of Western Ontario, Canada
University of Melbourne
Steno Diabetes Center
Maastricht University Medical Center
Information provided by (Responsible Party):
Prof John Petrie, University of Glasgow

Brief Summary:
The trial is conducted in the 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 HbA1c7.0%/53 mmol/mol) reduces atherosclerosis, as measured by progression of carotid IMT, in adults with confirmed type 1 diabetes aged 40 years and over at increased risk for cardiovascular disease.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: Metformin Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 502 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Phase 3 Study of Metformin in Adults With Type 1 Diabetes
Study Start Date : December 2011
Primary Completion Date : March 19, 2017
Study Completion Date : April 18, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Metformin
Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily
Drug: Metformin
3 years treatment duration
Other Name: Glucophage
Placebo Comparator: Placebo Drug: Placebo
3 years duration

Primary Outcome Measures :
  1. Change in averaged mean far wall common carotid artery IMT [ Time Frame: 0, 12 months, 24 months, 36 months ]

Secondary Outcome Measures :
  1. Change in HbA1c [ Time Frame: Baseline, Year 1, Year 2, Year 3 ]
  2. Change in LDL Cholesterol [ Time Frame: Baseline, Year 1, Year 2, Year 3 ]
  3. Change in albuminuria & estimated glomerular filtration rate [ Time Frame: Baseline, Year 1, Year 2, Year 3 ]
    Number of participants developing new microalbuminuria; change in absolute concentration

  4. Change in retinopathy stage [ Time Frame: Baseline, Year 3 ]
    ETDRS grade

  5. Change in weight [ Time Frame: Baseline, Year 1, Year 2, Year 3 ]
  6. Change in insulin dose [ Time Frame: Baseline, Year 1, Year 2, Year 3 ]
  7. Change in endothelial function [ Time Frame: Baseline, Year 1, Year 3 ]
    RHI units

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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 <90 ml/min per 1.73 m^3
  • Confirmed micro- or macroalbuminuria [according to local assays and reference ranges]
  • Hypertension (BP >=140/90mmHg 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01483560

Royal Melbourne Hospital
Melbourne, Australia
St Vincent's Hospital
Melbourne, Australia
Royal Prince Albert Hospital
Sydney, Australia
St Joseph's Health Care
Ontario, Canada
Ottawa Hospital Riverside Campus
Ottawa, Canada
Steno Diabetes Centre
Gentofte, Denmark
Maastricht University Medical Centre
Maastricht, Netherlands
United Kingdom
Aberdeen Royal Infirmary
Aberdeen, United Kingdom
Ayr Hospital
Ayr, United Kingdom, KA6 6DX
University Hospitals Bristol
Bristol, United Kingdom, BS2 8HW
Diabetes Support Unit, Ninewells Hospital and Medical School
Dundee, United Kingdom
University Hospital North Durham
Durham, United Kingdom
Edinburgh Royal Infirmary
Edinburgh, United Kingdom
Edinburgh Western Infirmary
Edinburgh, United Kingdom
Peninsula NIHR Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust
Exeter, United Kingdom
Stobhill Hospital, Diabetes Clinic
Glasgow, United Kingdom
Gloucestershire Royal Hospital
Gloucester, United Kingdom, GL1 3NN
Michael White Diabetes Centre, Hull Royal Infirmary
Hull, United Kingdom
Clinical Sciences Centre, University Hospital
Liverpool, United Kingdom
Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College Healthcare NHS Trust
London, United Kingdom
Wellcome Trust Clinical Research Facility, Manchester Royal Infirmary
Manchester, United Kingdom
Newcastle NIHR Clinical Research Facility, Royal Victoria Hospital
Newcastle, United Kingdom
Diabetes Clinical Research Centre, Plymouth
Plymouth, United Kingdom
Salford Royal NHS Foundation Trust
Salford, United Kingdom
Sponsors and Collaborators
University of Glasgow
NHS Greater Glasgow and Clyde
Juvenile Diabetes Research Foundation
Imperial College London
University of Wisconsin, Madison
University of Dundee
Merck Serono S.A., Geneva
Itamar-Medical, Israel
University of Western Ontario, Canada
University of Melbourne
Steno Diabetes Center
Maastricht University Medical Center
Principal Investigator: John Petrie, Prof University of Glasgow
Study Director: Helen Colhoun, Prof University of Dundee

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof John Petrie, Clinical Professor in Diabetic Medicine, University of Glasgow
ClinicalTrials.gov Identifier: NCT01483560     History of Changes
Other Study ID Numbers: GN10DI406
2011-000300-18 ( EudraCT Number )
First Posted: December 1, 2011    Key Record Dates
Last Update Posted: April 27, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Site specific participant data will be made available to the site PIs later in 2017, after the main publications.

Keywords provided by Prof John Petrie, University of Glasgow:
carotid IMT
LDL Cholesterol
endothelial function

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs