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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by University of Glasgow
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: April 1, 2013
Last verified: April 2013

November 23, 2011
April 1, 2013
December 2011
October 2016   (final data collection date for primary outcome measure)
Change in averaged mean far wall common carotid artery IMT [ Time Frame: 0, 12 months, 24 months, 36 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01483560 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
Phase 3 Study of Metformin in Adults With Type 1 Diabetes

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Diabetes Mellitus, Type 1
  • Drug: Metformin
    3 years treatment duration
    Other Name: Glucophage
  • Drug: Placebo
    3 years duration
  • Experimental: Metformin
    Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily
    Intervention: Drug: Metformin
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
500
December 2016
October 2016   (final data collection date for primary outcome measure)

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
Both
40 Years and older
No
Contact: John Petrie 00 44 141 330 3325 john.petrie@glasgow.ac.uk
United Kingdom,   Netherlands,   Canada,   Australia,   Denmark
 
NCT01483560
GN10DI406, 2011-000300-18
Yes
Prof John Petrie, University of Glasgow
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
University of Glasgow
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP