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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT01483560
First received: November 23, 2011
Last updated: May 20, 2015
Last verified: May 2015
  Purpose

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 Intervention Phase
Diabetes Mellitus, Type 1
Drug: Metformin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Phase 3 Study of Metformin in Adults With Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Glasgow:

Primary Outcome Measures:
  • Change in averaged mean far wall common carotid artery IMT [ Time Frame: 0, 12 months, 24 months, 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in HbA1c [ Time Frame: Baseline, Year 1, Year 2, Year 3 ] [ Designated as safety issue: No ]
  • Change in LDL Cholesterol [ Time Frame: Baseline, Year 1, Year 2, Year 3 ] [ Designated as safety issue: No ]
  • Change in albuminuria & estimated glomerular filtration rate [ Time Frame: Baseline, Year 1, Year 2, Year 3 ] [ Designated as safety issue: No ]
    Number of participants developing new microalbuminuria; change in absolute concentration

  • Change in retinopathy stage [ Time Frame: Baseline, Year 3 ] [ Designated as safety issue: No ]
    ETDRS grade

  • Change in weight [ Time Frame: Baseline, Year 1, Year 2, Year 3 ] [ Designated as safety issue: No ]
  • Change in insulin dose [ Time Frame: Baseline, Year 1, Year 2, Year 3 ] [ Designated as safety issue: No ]
  • Change in endothelial function [ Time Frame: Baseline, Year 1, Year 3 ] [ Designated as safety issue: No ]
    RHI units


Enrollment: 502
Study Start Date: December 2011
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01483560

Locations
Australia
Royal Melbourne Hospital
Melbourne, Australia
St Vincent's Hospital
Melbourne, Australia
Royal Prince Albert Hospital
Sydney, Australia
Canada
St Joseph's Health Care
Ontario, Canada
Ottawa Hospital Riverside Campus
Ottawa, Canada
Denmark
Steno Diabetes Centre
Gentofte, Denmark
Netherlands
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
Investigators
Principal Investigator: John Petrie, Prof University of Glasgow
Study Director: Helen Colhoun, Prof University of Dundee
  More Information

No publications provided

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
Study First Received: November 23, 2011
Last Updated: May 20, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
Canada: Canadian Institutes of Health Research
Australia: National Health and Medical Research Council
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Denmark: Danish Medicines Agency

Keywords provided by University of Glasgow:
REMOVAL
metformin
carotid IMT
LDL Cholesterol
endothelial function
retinopathy
HbA1c

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

ClinicalTrials.gov processed this record on May 29, 2015