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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000300-18 | EudraCT Number |
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| Name | Class |
|---|---|
| NHS Greater Glasgow and Clyde | OTHER |
| Juvenile Diabetes Research Foundation | OTHER |
| Imperial College London | OTHER |
| University of Wisconsin, Madison |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metformin | Experimental | Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily |
|
| Placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metformin | Drug | 3 years treatment duration |
|
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in HbA1c | Measured in accredited local laboratories participating in DCCT-aligned quality control programmes. | Baseline, Year 3 |
| Change in LDL Cholesterol | mmol/L Centrally assayed at the University of Glasgow |
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Inclusion Criteria:
AND 3 or more of the following ten CardioVascular Disease (CVD) risk factors:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Petrie, Prof | University of Glasgow | Principal Investigator |
| Helen Colhoun, Prof | University of Dundee | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Melbourne Hospital | Melbourne | Australia | ||||
| St Vincent's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38837240 | Derived | 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. | |
| 28615149 | Derived |
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Site specific participant data will be made available to the site PIs later in 2017, after the main publications.
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493 participants where enrolled and consented. All participants entered a 3 month Run In phase with placebo. Participants who remained eligible were randomly assigned to receive metformin or placebo for 3 years. 65 participants where ineligible to be randomized.
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| ID | Title | Description |
|---|---|---|
| FG000 | Metformin | Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily Metformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 9, 2015 | Sep 12, 2018 |
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| OTHER |
| University of Dundee | OTHER |
| Merck Serono S.A., Geneva | INDUSTRY |
| Itamar-Medical, Israel | INDUSTRY |
| University of Western Ontario, Canada | OTHER |
| University of Melbourne | OTHER |
| Steno Diabetes Center Copenhagen | OTHER |
| Maastricht University Medical Center | OTHER |
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| Placebo | Drug | 3 years duration |
|
| Baseline, Year 3 |
| Change in Estimated Glomerular Filtration Rate | Number of participants developing new microalbuminuria; change in absolute concentration Calculated using the MDRD equation1 based on creatinine measured in accredited local laboratories | 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 | Two color 45° field retinal photographs (fields 1 and 2) from each eye at 0 and 36 months graded at the University of Wisconsin Ocular Epidemiology Reading Center (OERC) using the modified Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Severity scale. | Baseline, Year 3 |
| Change in Weight | Measured at sites using calibrated weighing scales | Baseline, Year 1, Year 2, Year 3 |
| Change in Insulin Dose | Units/ kg body weight Extracted by study nurses from the Study Diary and reported on the study CRF using dedicated fields | Baseline, Year 1, Year 2, Year 3 |
| Change in Endothelial Function | In some centres (Arbitrary units) Reactive Hyperaemia Index using the ENDOPAT device (Itamar, Israel) | Baseline, Year 1, Year 3 |
| Melbourne |
| Australia |
| Royal Prince Albert Hospital | Sydney | Australia |
| St Joseph's Health Care | London | Ontario | Canada |
| Ottawa Hospital Riverside Campus | Ottawa | Canada |
| Steno Diabetes Centre | Gentofte Municipality | Denmark |
| Maastricht University Medical Centre | Maastricht | Netherlands |
| Aberdeen Royal Infirmary | Aberdeen | United Kingdom |
| Ayr Hospital | Ayr | KA6 6DX | United Kingdom |
| University Hospitals Bristol | Bristol | BS2 8HW | United Kingdom |
| 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 | GL1 3NN | United Kingdom |
| 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 |
| 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. |
Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Metformin | Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily Metformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group |
| BG001 | Placebo | Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| |||||||||||||||
| Region of Enrollment | Number | participants |
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| Diabetes Diagnosis Duration | Mean | Standard Deviation | years |
| |||||||||||||||
| Existing Cardiovascular Disease | Number | participants |
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| Baseline HbA1c | Number | mmol/mol |
| ||||||||||||||||
| Daily Insulin Dose | Number | units/kg |
| ||||||||||||||||
| BMI | Mean | Standard Deviation | kg/m2 |
| |||||||||||||||
| Blood Pressure | Mean | Standard Deviation | Systolic BP (mmHg) |
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| Total Cholesterol | Mean | Standard Deviation | mmol/L |
| |||||||||||||||
| eGFR | Mean | Standard Deviation | ml/min/1.73m2 |
| |||||||||||||||
| Diabetic Retinopathy | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | mm | 0, 12 months, 24 months, 36 months |
|
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Change in HbA1c | Measured in accredited local laboratories participating in DCCT-aligned quality control programmes. | Posted | Mean | Standard Deviation | %units | Baseline, Year 3 |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change in LDL Cholesterol | mmol/L Centrally assayed at the University of Glasgow | Posted | Mean | Standard Deviation | mmol/L | Baseline, Year 3 |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change in Estimated Glomerular Filtration Rate | Number of participants developing new microalbuminuria; change in absolute concentration Calculated using the MDRD equation1 based on creatinine measured in accredited local laboratories | Posted | Mean | Standard Deviation | ml/min/1.73m2 | Baseline, Year 1, Year 2, Year 3 |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Retinopathy and at Least a 2 Stage Progression in Retinopathy From Baseline to 36 Months | Two color 45° field retinal photographs (fields 1 and 2) from each eye at 0 and 36 months graded at the University of Wisconsin Ocular Epidemiology Reading Center (OERC) using the modified Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Severity scale. | Posted | Count of Participants | Participants | Baseline, Year 3 |
|
| ||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Weight | Measured at sites using calibrated weighing scales | Posted | Mean | Standard Deviation | kg | Baseline, Year 1, Year 2, Year 3 |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change in Insulin Dose | Units/ kg body weight Extracted by study nurses from the Study Diary and reported on the study CRF using dedicated fields | Posted | Mean | Standard Deviation | units/kg | Baseline, Year 1, Year 2, Year 3 |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Change in Endothelial Function | In some centres (Arbitrary units) Reactive Hyperaemia Index using the ENDOPAT device (Itamar, Israel) | Posted | Mean | Standard Deviation | RHI (Arbitrary units) | Baseline, Year 1, Year 3 |
|
|
Adverse event data collected from the date of consent until 30 days post last IMP dose, an average of 3 years.
Definition used same as clinical trials.gov
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Metformin | Oral Metformin (as Glucophage 500mg x 2 bd) titrated from initial 500mg to target 2000mg daily Metformin: 3 years treatment duration 219 of 428 randomised were assigned to Metformin Group | 5 | 219 | 34 | 219 | 112 | 219 |
| EG001 | Placebo | Placebo: 3 years duration 209 of the 428 randomised were assigned to Placebo | 2 | 209 | 31 | 209 | 52 | 209 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Metabolic and nutrition | Metabolism and nutrition disorders | Systematic Assessment |
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| Infections and Infestations | Infections and infestations | Systematic Assessment |
| ||
| Neoplasms | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Cerebral haemorrhage | Nervous system disorders | Systematic Assessment |
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| Gastrointestinal | Gastrointestinal disorders | Systematic Assessment |
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| Respiratory | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cardiac | Cardiac disorders | Systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | Systematic Assessment |
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| Coronary artery bypass graft | Surgical and medical procedures | Systematic Assessment |
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| Musculoskeletal | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Sudden Death | General disorders | Systematic Assessment |
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| Angiogram | Investigations | Systematic Assessment |
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| Circulatory collapse | Vascular disorders | Systematic Assessment |
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| Blood and Lymphatic | Blood and lymphatic system disorders | Systematic Assessment |
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| Immune System Disorder | Immune system disorders | Systematic Assessment |
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| Cerebrovascular accident | Nervous system disorders | Systematic Assessment |
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| hypoglycaemic coma | Nervous system disorders | Systematic Assessment |
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| Transient Ischaemic Attack | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| lung lobectomy | Surgical and medical procedures | Systematic Assessment |
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| coronary stent insertion | Surgical and medical procedures | Systematic Assessment |
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| Amputation revision | Surgical and medical procedures | Systematic Assessment |
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| Surgery (unspecified) | Surgical and medical procedures | Systematic Assessment |
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| Coronary angioplasty | Surgical and medical procedures | Systematic Assessment |
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| Spinal fusion Surgery | Surgical and medical procedures | Systematic Assessment |
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| Aortic valve repair | Surgical and medical procedures | Systematic Assessment |
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| Chest Pain | General disorders | Systematic Assessment |
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| Blood Glucose Fluctuation | Investigations | Systematic Assessment |
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| Ischaemic Necrosis | Vascular disorders | Systematic Assessment |
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| Peripheral Ischaemia | Vascular disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal | Gastrointestinal disorders | Systematic Assessment |
| ||
| Cardiovascular | Cardiac disorders | Systematic Assessment |
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| Neurological | Nervous system disorders | Systematic Assessment |
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| Hypersensitivity to Metformin | Product Issues | Systematic Assessment |
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| Opthalmic adverse events | Eye disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof John Petrie | University of Glasgow | +44 141 330 | 3325 | John.Petrie@glasgow.ac.uk |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 7, 2017 | Sep 12, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D012164 | Retinal Diseases |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D005128 | Eye Diseases |
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| ID | Term |
|---|---|
| D008687 | Metformin |
| ID | Term |
|---|---|
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
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| Between 18 and 65 years |
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| >=65 years |
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| Netherlands |
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| Denmark |
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| United Kingdom |
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| Australia |
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| 24 Months |
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| 36 Months |
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