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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01483560




Registration number
NCT01483560
Ethics application status
Date submitted
23/11/2011
Date registered
1/12/2011
Date last updated
19/06/2019

Titles & IDs
Public title
REducing With MetfOrmin Vascular Adverse Lesions in Type 1 Diabetes (REMOVAL)
Scientific title
Phase 3 Study of Metformin in Adults With Type 1 Diabetes
Secondary ID [1] 0 0
2011-000300-18
Secondary ID [2] 0 0
GN10DI406
Universal Trial Number (UTN)
Trial acronym
REMOVAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type 1 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Metformin
Treatment: Drugs - Placebo

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

Placebo Comparator: Placebo -


Treatment: Drugs: Metformin
3 years treatment duration

Treatment: Drugs: Placebo
3 years duration

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
0, 12 months, 24 months, 36 months
Secondary outcome [1] 0 0
Change in HbA1c - Measured in accredited local laboratories participating in DCCT-aligned quality control programmes.
Timepoint [1] 0 0
Baseline, Year 3
Secondary outcome [2] 0 0
Change in LDL Cholesterol - mmol/L Centrally assayed at the University of Glasgow
Timepoint [2] 0 0
Baseline, Year 3
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline, Year 1, Year 2, Year 3
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Year 3
Secondary outcome [5] 0 0
Change in Weight - Measured at sites using calibrated weighing scales
Timepoint [5] 0 0
Baseline, Year 1, Year 2, Year 3
Secondary outcome [6] 0 0
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
Timepoint [6] 0 0
Baseline, Year 1, Year 2, Year 3
Secondary outcome [7] 0 0
Change in Endothelial Function - In some centres (Arbitrary units) Reactive Hyperaemia Index using the ENDOPAT device (Itamar, Israel)
Timepoint [7] 0 0
Baseline, Year 1, Year 3

Eligibility
Key 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 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
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [2] 0 0
St Vincent's Hospital - Melbourne
Recruitment hospital [3] 0 0
Royal Prince Albert Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Ontario
Country [2] 0 0
Canada
State/province [2] 0 0
Ottawa
Country [3] 0 0
Denmark
State/province [3] 0 0
Gentofte
Country [4] 0 0
Netherlands
State/province [4] 0 0
Maastricht
Country [5] 0 0
United Kingdom
State/province [5] 0 0
Aberdeen
Country [6] 0 0
United Kingdom
State/province [6] 0 0
Ayr
Country [7] 0 0
United Kingdom
State/province [7] 0 0
Bristol
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Dundee
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Durham
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Edinburgh
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Exeter
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Glasgow
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Gloucester
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Hull
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Liverpool
Country [16] 0 0
United Kingdom
State/province [16] 0 0
London
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Manchester
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Newcastle
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Plymouth
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Other
Name
University of Glasgow
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
NHS Greater Glasgow and Clyde
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Juvenile Diabetes Research Foundation
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Imperial College London
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Wisconsin, Madison
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
University of Dundee
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Commercial sector/Industry
Name [6] 0 0
Merck Serono S.A., Geneva
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Commercial sector/Industry
Name [7] 0 0
Itamar-Medical, Israel
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
University of Western Ontario, Canada
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
University of Melbourne
Address [9] 0 0
Country [9] 0 0
Other collaborator category [10] 0 0
Other
Name [10] 0 0
Steno Diabetes Center Copenhagen
Address [10] 0 0
Country [10] 0 0
Other collaborator category [11] 0 0
Other
Name [11] 0 0
Maastricht University Medical Center
Address [11] 0 0
Country [11] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT01483560
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Petrie, Prof
Address 0 0
University of Glasgow
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications