The REMOVAL study: metformin in type 1 diabetes

Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Hormonal diseases [C19]

• Registration Number: EUCTR2011-000300-18-GB
• Lead Sponsor: HS Greater Glasgow and Clyde

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-08-17
• Study Completion: 2017-02-17
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 493

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 < 10.0% (53-86 mmol/mol)
AND three of more of the following ten CVD risk factors:
- BMI greater than 27kg/m^2
- current HbA1c > 8.0% (64mmol/mol)
- known CVD/peripheral vascular disease
- current smoker
- estimated glomerular filtration rate < 90 ml/min per 1.73 m^2
- confirmed micro- or macroalbuminuria [according to local assays and reference ranges]
- hypertension (BP of 140/90mmHg or above or established on antihypertensive treatment)
- dyslipidaemia [total cholesterol = 5.0 mmol/L (200 mg/dL); OR HDL cholesterol <1.2 (46 mg/dL)mmol/L [men or < 1.3 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
* 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

- 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 < 45ml/min/1.73m^2

- Contraindications to metformin [hepatic impairment (ALT > 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 <10.0 g/dL)

- Ongoing treatment with oral steroids, pramlintide or GLP-1 agonist therapy

- Hypoglycaemia unawareness confirme as significant by site Prinicipal Investigator

- Impaired cognitive function/unable to give informed consent

- Previous carotid surgery or inability to capture adequate carotid images

- Gastroparesis (on gastric emptying studies) confirmed as significant by site Principal Investigator OR more than two hospital admissions with unexplained vomiting in last year.

- History of biochemically-confirmed lactic acidosis (>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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified