Effect of Metformin in Patients With Type-1 Diabetes With Inadequate Glycaemic Control by Insulin and Diet

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

Effect of Metformin On Glycaemic Control and Non-Glycaemic Cardiovascular Risk-Factors in Patients With Type-1 Diabetes, With Long-Standing Inadequate Glycaemic Control by Insulin and Diet

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00118937
• Other study ID #: Type-1-Metformin
• Status: Completed
• Phase: Phase 4
• First received: July 1, 2005
• Last updated: December 5, 2008
• Start date: December 2003
• Est. completion date: August 2006

Study information

• Verified date: December 2008
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines Agency
• Study type: Interventional

Clinical Trial Summary

Ninety percent of patients with type-1-diabetes will develop late-diabetic complications in the eyes, kidneys, nervous- or cardiovascular-system. Poor glycaemic control is an important risk-factor for development of these late-diabetic complications. The Diabetes Control and Complications Trial (DCCT)-study showed, that improved glycaemic control can prevent the development and progression of these late-diabetic complications. Until now treatment with insulin- and diet-therapy has been the only treatment-modalities available to improve the glycaemic control in patients with type-1-diabetes. A substantial number of these patients still have long-standing poor glycaemic control despite intensive treatment with insulin- and diet-therapy.

The antidiabetic drug metformin has shown to be able to improve the glycaemic control in combination with insulin and furthermore reduce both mortality and the risk of developing cardiovascular disease in patients with type-2-diabetes.

Only few small studies have investigated the effect of treatment with metformin in patients with type-1-diabetes. These studies have suggested a positive effect of metformin in these patients too.

Method:

100 patients with type-1-diabetes with persistent poor glycaemic control i.e. HbA1c > 8.5% during the last 12 months are eligible. Patients are treated for one month with placebo. Hereafter half of the patients will be treated with metformin and the other half continues with placebo for 12 months both as add-on therapy. All patients are continuing ongoing treatment with insulin throughout the study. Before and after the start of treatment with metformin the effect on glycaemic control and other known risk-factors for development of cardiovascular disease i. e. blood-pressure, fasting lipids, urine-albumine-excretion, endothelial dysfunction, inflammation, fibrinolysis etc. is assessed.

This study will show if treatment with metformin can improve the glycaemic control and hereby the prognosis of patients with type-1-diabetes with persistent poor glycaemic control despite intensive treatment with insulin- and diet-therapy. This group of patients suffers the highest risk of developing late-diabetic complications with reduced quality of life and life-expectancy as a consequence.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: August 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HbA1c > 8.5% for more than one year prior to enrolment.

• Diabetes-duration > 5 years.

• Age at onset of diabetes < 35 years

• Fasting C-peptide < 300 pmol/l

• Age > 18 years at enrolment.

Exclusion Criteria:

• Clinical or biochemical signs of kidney-, liver- or heart-failure.

• Other coexisting serious morbidity, which will affect the study-participation or outcome of the study i.e. cancer.

• Known abuse of any medication or alcohol

• Hypoglycaemia unawareness.

• Pregnancy or planned pregnancy in the study-period.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1

Intervention

Drug:
• Metformin
Tablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose).
• Placebo.
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day.
• Placebo.
Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Steno Diabetes Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c - difference between final visit and baseline.
Secondary	Absolute HbA1c
Secondary	Number of mild and severe hypoglycaemia with or without measurements of blood-glucose.
Secondary	Insulin-dose
Secondary	The following parameters are measured at baseline and at the final visit after 12 months of intervention:
Secondary	Plasma-PAI-antigen and -activity, t-PA-antigen- and activity.
Secondary	Plasma-fibrinogen
Secondary	Serum-albumin
Secondary	Markers of endothelial dysfunction: Von Willebrand Factor, ICAM, VCAM, Amadori-protein, selectin and endothelin.
Secondary	Plasma-homocysteine
Secondary	Asymmetric DiMethylArginine - ADMA
Secondary	Urine-albumin-excretion in three 24 hour urine-collections
Secondary	Blood-pressure in the sitting position after 10 minutes of rest.
Secondary	Fasting lipid-profile (total-cholesterol, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol and triglycerides), small-dense-LDL, Lp(a) and Apo-B100.
Secondary	Weight, BMI and Waist-hip-ratio
Secondary	White blood-cell-count, hs-CRP, Interleukin-6 and TNF-alfa.
Secondary	Serum-creatinine, sodium, potassium, ASAT, alkaline phosphatase, Factor 2, 7, 10, Cobalamin, Erythrocyte-folate and Haemoglobin-concentration.
Secondary	Extra blood- and urine-samples will be stored at -80 degrees Celsius for potential extra analyses after closure of the study. DNA will be stored for later pharmaco-genetic analysis.