People with type 1 diabetes with risk factors for cardiovascular disease MedDRA version: 14.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Glucophage 500mg
Product Name: Metformin
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Metformin hydrochloride
Sponsors
NHS Greater Glasgow and Clyde
University of Glasgow
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Type 1 Diabetes for five years or more* (defined as diagnosis below age 35 AND insulin use within 1 year of diagnosis) - Age = 40 years - 7.0 = HbA1c 8.0% (64mmol/mol) - known CVD/peripheral vascular disease - current smoker - estimated glomerular filtration rate 20 years * defines as diagnosis below age 40 years AND insulin use within 1 year of diagnosis Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 450 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Women of child-bearing age (i.e. continuing menstrual cycle) not using effective contraception. For women of childbearing age in REMOVAL, acceptable forms of effective contraception include:* * Established use of oral, injected or implanted hormonal methods of contraception * Placement of an intrauterine device (IUD) or intrauterine system (IUS). [Consideration should be given to the type of device or system being used, as there are higher failure rates quoted for certain types, e.g. steel or copper wire] * Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) – must be combined with spermicidal foam/gel/film/cream/suppository. * Sole male partner has been sterilised with appropriate post-vasectomy documentation of the absence of sperm in ejaculate. * True abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, post-ovulation methods) and withdrawal are not acceptable methods of contraception. - Pregnancy and/or lactation; planning to get pregnant - Patients with Acute Coronary Syndrome or Stroke/TIA within the last three months - Symptomatic angina on mild or moderate exertion - Stage 3 or 4 heart failure defined according to the NYHA criteria - Estimated glomerular filtration rate 3.0 times ULN), known hypersensitivity to metformin, acute illness such as dehydration, severe infection, shock, acute cardiac failure, suspected tissue hypoxia] - Metformin treatment for more than three months within the last two years - Anaemia (haemoglobin 5.0 mmol/L) - Any coexistent life threatening condition including prior diagnosis of cancer within two years - History of alcohol problem or drug abuse - Diabetes or than Type 1 diabetes (e.g. secondary to pancreatitis, pancreatectomy or other primary pancreatic diseases) - Involvement in a clinical trial involving an investigational medicinal product within the last six months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of REMOVAL is to test whether metformin tablets added in with insulin treatment in type 1 diabetes can prevent the early blood vessel complications which lead to heart attacks and strokes.;Secondary Objective: REMOVAL will also examine whether insulin treatment in type 1 diabetes can help to improve blood glucose and cholesterol, stabilise weight and prevent other complications. ;Primary end point(s): Mixed effects regression model estimates of between-group cIMT difference over time, with 95% confidence intervals and p-values. Primary outcome regression model extended to assess whether metabolic effects could explain differences in progression of cIMT.;Timepoint(s) of evaluation of this end point: Carotid IMT will be measured at baseline and at years 1, 2 and 3. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: (i) HbA1c; (ii) LDL cholesterol; (iii) albuminuria & estimated glomerular filtration rate; (iv) retinopathy stage (ETDRS stage = Early Treatment Diabetic Retinopathy Study); (v) weight; (vi) insulin dose; (vii) endothelial function (in some centres). ;Timepoint(s) of evaluation of this end point: As for primary endpoint (baseline and annually over three years) | — |
Countries
Australia, Canada, Denmark, Netherlands, United Kingdom
Contacts
Public ContactResearch and Development
NHS Greater Glasgow and Clyde
Outcome results
None listed