NCT01483560

Brief Summary

The trial is conducted in the United Kingdom (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 HbA1c 7.0%/53 mmol/mol) reduces atherosclerosis, as measured by progression of carotid intima-media thickness (cIMT), in adults with confirmed type 1 diabetes aged 40 years and over at increased risk for cardiovascular disease.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
493

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Dec 2011

Longer than P75 for phase_3

Geographic Reach
5 countries

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 23, 2011

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 1, 2011

Completed
Same day until next milestone

Study Start

First participant enrolled

December 1, 2011

Completed
5.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 19, 2017

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

April 18, 2017

Completed
2.1 years until next milestone

Results Posted

Study results publicly available

June 3, 2019

Completed
Last Updated

June 19, 2019

Status Verified

June 1, 2019

Enrollment Period

5.3 years

First QC Date

November 23, 2011

Results QC Date

September 20, 2018

Last Update Submit

June 4, 2019

Conditions

Diabetes Mellitus, Type 1

Keywords

REMOVALmetformincarotid IMTLDL Cholesterolendothelial functionretinopathyHbA1c

Outcome Measures

Primary Outcomes (1)

  • Change in Averaged Mean Far Wall Common Carotid Artery Intima-media Thickness (cIMT)

    Progression of averaged mean far wall common carotid artery intima media thickness IMT (mean cIMT) measured using B mode ultrasonography with a 7.0 MHz or higher broadband linear array transducer and concurrent recording of 3-lead electrocardiogram (ECG). Longitudinal images of the common carotid artery will be obtained at anterior, lateral and posterior angles at baseline, 12, 24 and 36 months using Meijer's arc to standardize the transducer angle.

    0, 12 months, 24 months, 36 months

Secondary Outcomes (7)

  • Change in HbA1c

    Baseline, Year 3

  • Change in LDL Cholesterol

    Baseline, Year 3

  • Change in Estimated Glomerular Filtration Rate

    Baseline, Year 1, Year 2, Year 3

  • Number of Participants With Retinopathy and at Least a 2 Stage Progression in Retinopathy From Baseline to 36 Months

    Baseline, Year 3

  • Change in Weight

    Baseline, Year 1, Year 2, Year 3

  • +2 more secondary outcomes

Study Arms (2)

Metformin

EXPERIMENTAL

Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily

Drug: Metformin

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

MetforminDRUG

3 years treatment duration

Also known as: Glucophage
Metformin
PlaceboDRUG

3 years duration

Placebo

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Type 1 Diabetes for five years or more\*
  • Age 40 years or above
  • =\< HbA1c \<10.0% (53 - 86 mmol/mol)
  • AND 3 or more of the following ten CardioVascular Disease (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 (eGFR) \<90 ml/min per 1.73 m\^3
  • Confirmed micro- or macroalbuminuria \[according to local assays and reference ranges\]
  • Hypertension (BP \>=140/90 millimeters of mercury (mmHg) 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Royal Melbourne Hospital

Melbourne, Australia

Location

St Vincent's Hospital

Melbourne, Australia

Location

Royal Prince Albert Hospital

Sydney, Australia

Location

St Joseph's Health Care

London, Ontario, Canada

Location

Ottawa Hospital Riverside Campus

Ottawa, Canada

Location

Steno Diabetes Centre

Gentofte Municipality, Denmark

Location

Maastricht University Medical Centre

Maastricht, Netherlands

Location

Aberdeen Royal Infirmary

Aberdeen, United Kingdom

Location

Ayr Hospital

Ayr, KA6 6DX, United Kingdom

Location

University Hospitals Bristol

Bristol, BS2 8HW, United Kingdom

Location

Diabetes Support Unit, Ninewells Hospital and Medical School

Dundee, United Kingdom

Location

University Hospital North Durham

Durham, United Kingdom

Location

Edinburgh Royal Infirmary

Edinburgh, United Kingdom

Location

Edinburgh Western Infirmary

Edinburgh, United Kingdom

Location

Peninsula NIHR Clinical Research Facility, Royal Devon and Exeter NHS Foundation Trust

Exeter, United Kingdom

Location

Stobhill Hospital, Diabetes Clinic

Glasgow, United Kingdom

Location

Gloucestershire Royal Hospital

Gloucester, GL1 3NN, United Kingdom

Location

Michael White Diabetes Centre, Hull Royal Infirmary

Hull, United Kingdom

Location

Clinical Sciences Centre, University Hospital

Liverpool, United Kingdom

Location

Clinical Investigation Unit, International Centre for Circulatory Health, Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Wellcome Trust Clinical Research Facility, Manchester Royal Infirmary

Manchester, United Kingdom

Location

Newcastle NIHR Clinical Research Facility, Royal Victoria Hospital

Newcastle, United Kingdom

Location

Diabetes Clinical Research Centre, Plymouth

Plymouth, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, United Kingdom

Location

Related Publications (2)

  • El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.

    PMID: 38837240DERIVED

  • Petrie JR, Chaturvedi N, Ford I, Brouwers MCGJ, Greenlaw N, Tillin T, Hramiak I, Hughes AD, Jenkins AJ, Klein BEK, Klein R, Ooi TC, Rossing P, Stehouwer CDA, Sattar N, Colhoun HM; REMOVAL Study Group. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017 Aug;5(8):597-609. doi: 10.1016/S2213-8587(17)30194-8. Epub 2017 Jun 11.

    PMID: 28615149DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Retinal Diseases

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System DiseasesEye Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Results Point of Contact

Title
Prof John Petrie
Organization
University of Glasgow
John.Petrie@glasgow.ac.uk
+44 141 330

Study Officials

  • John Petrie, Prof

    University of Glasgow

    PRINCIPAL INVESTIGATOR

  • Helen Colhoun, Prof

    University of Dundee

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Clinical Professor in Diabetic Medicine

Study Record Dates

First Submitted

November 23, 2011

First Posted

December 1, 2011

Study Start

December 1, 2011

Primary Completion

March 19, 2017

Study Completion

April 18, 2017

Last Updated

June 19, 2019

Results First Posted

June 3, 2019

Record last verified: 2019-06

Data Sharing

IPD Sharing
Will share

Site specific participant data will be made available to the site PIs later in 2017, after the main publications.

Locations

GB(17)NL(1)CA(2)AU(3)DK(1)