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
  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


Estimated Enrollment: 500
Study Start Date: December 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: October 2016 (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

Contacts
Contact: John Petrie 00 44 141 330 3325 john.petrie@glasgow.ac.uk

Locations
Australia
St Vincent's Hospital Recruiting
Melbourne, Australia
Contact: Alicia Jenkins       jenkinsa@medstv.unimelb.edu.au   
Principal Investigator: Alicia Jenkins         
Sub-Investigator: David O'Neal         
Royal Melbourne Hospital Recruiting
Melbourne, Australia
Contact: Peter Colman       peter.colman@mh.org.au   
Principal Investigator: Peter Colman         
Royal Prince Albert Hospital Recruiting
Sydney, Australia
Contact: Stephen Twigg       stwigg@med.usyd.edu.au   
Principal Investigator: Stephen Twigg         
Canada
St Joseph's Health Care Recruiting
Ontario, Canada
Contact: Irene Hramiak       irene.hramiak@sjhc.london.on.ca   
Principal Investigator: Irene Hramiak         
Ottawa Hospital Riverside Campus Not yet recruiting
Ottawa, Canada
Contact: TC Ooi       tcooi@toh.on.ca   
Principal Investigator: TC Ooi         
Denmark
Steno Diabetes Centre Not yet recruiting
Gentofte, Denmark
Contact: Peter Rossing       ltar@steno.dk   
Principal Investigator: Peter Rossing         
Netherlands
Maastricht University Medical Centre Recruiting
Maastricht, Netherlands
Contact: Coen Stehouwer       cda.stehouwer@mumc.nl   
Principal Investigator: Coen Stehouwer         
Sub-Investigator: Martijn Brouwers         
United Kingdom
Aberdeen Royal Infirmary Not yet recruiting
Aberdeen, United Kingdom
Contact: Donald Pearson       donald.pearson@nhs.net   
Principal Investigator: Donald Pearson         
Diabetes Support Unit, Ninewells Hospital and Medical School Recruiting
Dundee, United Kingdom
Contact: Graham Leese       graham.leese@nhs.net   
Principal Investigator: Graham Leese         
University Hospital North Durham Recruiting
Durham, United Kingdom
Contact: Kamal Abouglilia       kamal.abouglila@cddft.nhs.uk   
Principal Investigator: Kamal Abouglilia         
Edinburgh Western Infirmary Not yet recruiting
Edinburgh, United Kingdom
Contact: John McKnight       john.mcknight@nhs.net   
Principal Investigator: John McKnight         
Edinburgh Royal Infirmary Not yet recruiting
Edinburgh, United Kingdom
Contact: Alan Jaap       alan.jaap@nhslothian.scot.nhs.uk   
Principal Investigator: Alan Jaap         
Peninsula NIHR Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust Recruiting
Exeter, United Kingdom
Contact: Roderick Warren       roderick.warren@nhs.net   
Principal Investigator: Roderick Warren         
Sub-Investigator: Angela Shore         
Stobhill Hospital, Diabetes Clinic Recruiting
Glasgow, United Kingdom
Contact: John Petrie    0044 141 330 3325    john.petrie@glasgow.ac.uk   
Principal Investigator: Gerard McKay         
Michael White Diabetes Centre, Hull Royal Infirmary Recruiting
Hull, United Kingdom
Contact: Steve Atkin       stephen.atkin@hyms.ac.uk   
Principal Investigator: Steve Atkin         
Clinical Sciences Centre, University Hospital Not yet recruiting
Liverpool, United Kingdom
Contact: John Wilding       j.p.h.wilding@liverpool.ac.uk   
Principal Investigator: John Wilding         
Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College Healthcare NHS Trust Recruiting
London, United Kingdom
Contact: Nick Oliver       nick.oliver@imperial.ac.uk   
Principal Investigator: Nick Oliver         
Wellcome Trust Clinical Research Facility, Manchester Royal Infirmary Recruiting
Manchester, United Kingdom
Contact: Rob Davies       rob.davies@cmft.nhs.uk   
Principal Investigator: Martin Gibson         
Newcastle NIHR Clinical Research Facility, Royal Victoria Hospital Recruiting
Newcastle, United Kingdom
Contact: Mark Walker       mark.walker@newcastle.ac.uk   
Principal Investigator: Mark Walker         
Diabetes Clinical Research Centre, Plymouth Recruiting
Plymouth, United Kingdom
Contact: Ann Millward       ann.millward@pms.ac.uk   
Principal Investigator: Ann Millward         
Sub-Investigator: Mike Eaton         
Salford Royal NHS Foundation Trust Recruiting
Salford, United Kingdom
Contact: Martin Gibson       martin.gibson@manchester.ac.uk   
Principal Investigator: Martin Gibson         
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: April 1, 2013
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
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014