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

Overview[ - collapse ][ - ]

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.
ConditionDiabetes Mellitus, Type 1
InterventionDrug: Metformin
Drug: Placebo
PhasePhase 3
SponsorUniversity of Glasgow
Responsible PartyUniversity of Glasgow
ClinicalTrials.gov IdentifierNCT01483560
First ReceivedNovember 23, 2011
Last UpdatedApril 1, 2013
Last verifiedApril 2013

Tracking Information[ + expand ][ + ]

First Received DateNovember 23, 2011
Last Updated DateApril 1, 2013
Start DateDecember 2011
Estimated Primary Completion DateDecember 2016
Current Primary Outcome MeasuresChange in averaged mean far wall common carotid artery IMT [Time Frame: 0, 12 months, 24 months, 36 months] [Designated as safety issue: No]
Current 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

Descriptive Information[ + expand ][ + ]

Brief TitleREducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
Official TitlePhase 3 Study of Metformin in Adults With Type 1 Diabetes
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
ConditionDiabetes Mellitus, Type 1
InterventionDrug: Metformin
3 years treatment duration
Other Names:
GlucophageDrug: Placebo
3 years duration
Study Arm (s)
  • Experimental: Metformin
    Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily
  • Placebo Comparator: Placebo

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment500
Estimated Completion DateDecember 2016
Estimated Primary Completion DateOctober 2016
Eligibility 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
GenderBoth
Ages40 Years
Accepts Healthy VolunteersNo
ContactsContact: John Petrie
00 44 141 330 3325
john.petrie@glasgow.ac.uk
Location CountriesAustralia, Canada, Denmark, Netherlands, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT01483560
Other Study ID NumbersGN10DI406
Has Data Monitoring CommitteeYes
Information Provided ByUniversity of Glasgow
Study SponsorUniversity of Glasgow
CollaboratorsNHS Greater Glasgow and Clyde
Juvenile Diabetes Research Foundation
Imperial College London
University of Wisconsin School of Medicine and Public Health
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 GlasgowStudy Director: Helen Colhoun, Prof University of Dundee
Verification DateApril 2013

Locations[ + expand ][ + ]

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