Reducing vascular damage with metformin in juvenile diabetes

Phase 1

• Conditions: Type 1 diabetes mellitus; MedDRA version: 18.1Level: LLTClassification code 10063623Term: Type I diabetes mellitus inadequate controlSystem Organ Class: 100000004861; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2011-000300-18-NL
• Lead Sponsor: Maastricht University Medical Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-01-05
• Study Completion: 2017-02-17
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 493

Inclusion Criteria

Type 1 diabetes for five years or more*; age = 40 years; 7.0 = HbA1c < 10.0% (53-86 mmol/mol)

AND three or more of the following ten CVD risk factors:
(i) BMI = 27 kg/m2
(ii) current HbA1c > 8.0% (64 mmol/mol)
(iii) known CVD/ peripheral vascular disease
(iv) current smoker
(v) eGFR < 90 ml/ min/ 1.73 m2
(vi) micro- (or macro-) albuminuria [according to local assays and reference ranges]
(vii) hypertension (BP¬=140/ 90 mmHg; or established on antihypertensive treatment)
(viii) dyslipidaemia [total cholesterol=5.0 mmol/L (200 mg/dL); or HDL cholesterol<1.20 mmol/L (46 mg/dL) [men] HDL cholesterol<1.30 mmol/L (50 mg/dL) [women]; or fasting triglycerides=1.7 mmol/L (150 mg/dL); or established on lipid-lowering treatment
(ix) strong family history of CVD (at least one parent, sibling or aunt/uncle with myocardial infarction, CABG or stroke aged < 60 years)
(x) duration of diabetes > 20 years.

* Type 1 diabetes is defined 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:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 31
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

(i) Women of childbearing age (i.e. continuing menstrual cycle) not using effective contraception
(ii) Pregnancy and/or lactation; planning to get pregnant or not using effective contraception
(iii) Patients with Acute Coronary Syndrome or Stroke/ Transient Ischaemic Attack within the last three months
(iv) Symptomatic angina on mild or moderate exertion
(v) Stage 3 or 4 heart failure defined according to the NYHA criteria
(vi) Estimated glomerular filtration rate < 45 ml/min/1.73m2 (MDRD)
(vii) Contraindications to metformin
- hepatic impairment (ALT > 3.0 times ULN)
- known hypersensitivity to metformin
- acute illness [dehydration, severe infection, shock, acute cardiac failure]
- suspected tissue hypoxia
(viii) Metformin treatment for more than three months within last two years
(ix) Anaemia (haemoglobin < 10.0 g/dL)
(x) Ongoing treatment with oral steroids, pramlintide or GLP-1 agonist therapy
(xi) Hypoglycaemia unawareness confirmed as significant by site Principal Investigator
(xii) Impaired cognitive function/ unable to give informed consent
(xiii) Previous carotid surgery or inability to capture adequate carotid images
(xiv) Gastroparesis (on gastric emptying studies) confirmed as significant by site Principal Investigator OR more than two hospital admissions with unexplained vomiting in last year
(xv) history of biochemically-confirmed acidosis (lactate > 5.0 mmol/L)
(xvi) Any coexistent life-threatening condition including diagnosis of cancer within prior two years
(xvii) history of alcohol problem or drug abuse
(xviii) diabetes other than type 1 diabetes (e.g. secondary to pancreatitis, pancreatectomy or primary pancreatic disease)
(xix) 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