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

Sponsored by:	Steno Diabetes Center
Information provided by:	Steno Diabetes Center
ClinicalTrials.gov Identifier:	NCT00118937

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	Intervention	Phase
Diabetes Mellitus, Type 1	Drug: Metformin Drug: Placebo.	Phase IV

MedlinePlus related topics: Diabetes Diabetes Complications Diabetes Type 1 Diets Urine and Urination

Drug Information available for: Insulin Metformin Metformin hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by Steno Diabetes Center:

Primary Outcome Measures:

HbA1c - difference between final visit and baseline.

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.

Enrollment:	100
Study Start Date:	December 2003
Study Completion Date:	August 2006
Primary Completion Date:	August 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Placebo Comparator Single-blind placebo run-in period. Duration one month.	Drug: Placebo. Tablet Placebo (corresponding to 500 mg metformin). Dosage: 1 tablet per day.
2: Active Comparator Metformin 2000 mg, double-masked randomized during 12 months.	Drug: Metformin Tablet Metformin 500 mg, Dosage: 1000 mg two times daily (2000 mg total daily dose).
3: Placebo Comparator Placebo, double-masked randomized during 12 months.	Drug: Placebo. Tablet Placebo (corresponding to 500 mg metformin). Dosage: 2 tablets two times daily.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118937

Sponsors and Collaborators

Steno Diabetes Center

Investigators

Study Chair:	Allan A Vaag, M.D., chief physician	Steno Diabetes Center
Principal Investigator:	Soeren S Lund, M. D.	Steno Diabetes Center

More Information

No publications provided by Steno Diabetes Center

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Lund SS, Tarnow L, Astrup AS, Hovind P, Jacobsen PK, Alibegovic AC, Parving I, Pietraszek L, Frandsen M, Rossing P, Parving HH, Vaag AA. Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. PLoS ONE. 2008;3(10):e3363. Epub 2008 Oct 9.

Study ID Numbers:	Type-1-Metformin
Study First Received:	July 1, 2005
Last Updated:	December 5, 2008
ClinicalTrials.gov Identifier:	NCT00118937 History of Changes
Health Authority:	Denmark: Danish Medicines Agency

Study placed in the following topic categories:

Hypoglycemic Agents
Autoimmune Diseases
Metabolic Diseases
Diabetes Mellitus, Type 1
Metformin
Diabetes Mellitus

Endocrine System Diseases
Diabetes Mellitus Type 1
Endocrinopathy
Glucose Metabolism Disorders
Metabolic Disorder
Insulin

Additional relevant MeSH terms:

Hypoglycemic Agents
Autoimmune Diseases
Metabolic Diseases
Immune System Diseases
Diabetes Mellitus, Type 1
Physiological Effects of Drugs

Metformin
Diabetes Mellitus
Endocrine System Diseases
Glucose Metabolism Disorders
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009