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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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)
Timepoint [1] 0 0
0, 12 months, 24 months, 36 months
Secondary outcome [1] 0 0
Change in HbA1c
Timepoint [1] 0 0
Baseline, Year 3
Secondary outcome [2] 0 0
Change in LDL Cholesterol
Timepoint [2] 0 0
Baseline, Year 3
Secondary outcome [3] 0 0
Change in Estimated Glomerular Filtration Rate
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
Timepoint [4] 0 0
Baseline, Year 3
Secondary outcome [5] 0 0
Change in Weight
Timepoint [5] 0 0
Baseline, Year 1, Year 2, Year 3
Secondary outcome [6] 0 0
Change in Insulin Dose
Timepoint [6] 0 0
Baseline, Year 1, Year 2, Year 3
Secondary outcome [7] 0 0
Change in Endothelial Function
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
Sex
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
1/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/04/2017
Sample size
Target
Accrual to date
Final
493
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/ct2/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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01483560