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

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

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Diabetes Mellitus, Type 1
Intervention	Drug: Metformin Drug: Placebo. Drug: Placebo.
Phase	Phase 4
Sponsor	Steno Diabetes Center
Responsible Party	Steno Diabetes Center
ClinicalTrials.gov Identifier	NCT00118937
First Received	July 1, 2005
Last Updated	December 5, 2008
Last verified	December 2008

Tracking Information[ + expand ][ + ]

First Received Date	July 1, 2005
Last Updated Date	December 5, 2008
Start Date	December 2003
Estimated Primary Completion Date	August 2006
Current Primary Outcome Measures	HbA1c - difference between final visit and baseline.
Current Secondary Outcome Measures	Absolute HbA1c Number of mild and severe hypoglycaemia with or without measurements of blood-glucose. Insulin-dose The following parameters are measured at baseline and at the final visit after 12 months of intervention: Plasma-PAI-antigen and -activity, t-PA-antigen- and activity. Plasma-fibrinogen Serum-albumin Markers of endothelial dysfunction: Von Willebrand Factor, ICAM, VCAM, Amadori-protein, selectin and endothelin. Plasma-homocysteine Asymmetric DiMethylArginine - ADMA Urine-albumin-excretion in three 24 hour urine-collections Blood-pressure in the sitting position after 10 minutes of rest. Fasting lipid-profile (total-cholesterol, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol and triglycerides), small-dense-LDL, Lp(a) and Apo-B100. Weight, BMI and Waist-hip-ratio White blood-cell-count, hs-CRP, Interleukin-6 and TNF-alfa. Serum-creatinine, sodium, potassium, ASAT, alkaline phosphatase, Factor 2, 7, 10, Cobalamin, Erythrocyte-folate and Haemoglobin-concentration. 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.

Descriptive Information[ + expand ][ + ]

Brief Title	Effect of Metformin in Patients With Type-1 Diabetes With Inadequate Glycaemic Control by Insulin and Diet
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
Brief 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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 4
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Diabetes Mellitus, Type 1
Intervention	Drug: Metformin Tablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose). Drug: Placebo. Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day. Drug: Placebo. Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.
Study Arm (s)	Placebo Comparator: 1 Single-blind placebo run-in period. Duration one month. Active Comparator: 2 Metformin 2000 mg, double-masked randomized during 12 months. Placebo Comparator: 3 Placebo, double-masked randomized during 12 months.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	100
Estimated Completion Date	August 2006
Estimated Primary Completion Date	August 2006
Eligibility Criteria	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.
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Not Provided

Administrative Information[ + expand ][ + ]

NCT Number	NCT00118937
Other Study ID Numbers	Type-1-Metformin
Has Data Monitoring Committee	Not Provided
Information Provided By	Steno Diabetes Center
Study Sponsor	Steno Diabetes Center
Collaborators	Not Provided
Investigators	Study Chair: Allan A Vaag, M.D., chief physician Steno Diabetes CenterPrincipal Investigator: Soeren S Lund, M. D. Steno Diabetes Center
Verification Date	December 2008