Type 2 diabetes mellitus, impaired glucose metabolism
Conditions
Interventions
Participants will be randomized into 1 of the following 4 treatment groups for a 52-week intervention:
1. Rosiglitazone 8 mg daily and valsartan-placebo
2. Valsartan 320 mg daily and rosiglitazon-placebo
3. Rosiglitazone 8 mg daily and valsartan 320 mg daily
4. Rosiglitazon-placebo and valsartan-placebo.
Amendment 2007:
Participants will be randomized into 1 of the 2 treatment groups for a 26-week intervention:
1. Valsartan 320 mg daily
Sponsors
VU University Medical Center,
Amsterdam
The Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: Male and female subjects (aged 35-70 years) with impaired fasting glucose (IFG; fasting plasma glucose 6.1 or higher and less than 7.0 mmol/l) and/or subjects with IFG (fasting plasma glucose 5.6 or higher and less than 7.0 mmol/l) ánd a family history of DM2 (i.e. first and second degree (i.e. grandparents) relatives), and/or impaired glucose tolerance (IGT; 2-h plasma glucose during 75-g oral glucose tolerance test 7.8-11.1 mmol/l) are eligible.
Exclusion criteria
Exclusion criteria: Drug use: 1. Current use of ACE-I, ARB and/or TZDs and inability to discontinue these drugs; 2. Known hypersensitivity to any of the study drugs; 3. Prior use of blood glucose lowering medications except during pregnancy; 4. Use of systemic glucocorticoids or niacin. Cardiovascular co-morbidities: 1. Ejection fraction known to be 50% stenosis in >=2 major coronary arteries, or ST depression of >=2mm, or a positive nuclear test, previous coronary angioplasty, stent or bypass; previous limb bypass or vessel angioplasty or angiographic evidence of >50% stenosis, or intermittent claudication with an ankle/arm pressure <=0.8); 2. Uncontrolled hypertension requiring ACE I or ARB. Other Criteria: 1. History of diabetes (except gestational DM) or on antidiabetic medication; 2. Renal or Hepatic Disease: A. Renal artery stenosis; B. Creatinine clearance <40 ml/min or serum creatinine 200 umol/l or higher; C. Clinical proteinuria (1 or above, + proteinuria on dipstick or 300 mg and above albuminuria/day, in the absence of urine); D. Measured alanine transferase (ALT) 2.5 or more times the upper limit of normal; E. Active liver disease including jaundice, chronic hepatitis, previous liver transplant. 3. Major illness with life expectancy < 5 years or that may interfere with participation; 4. Use of another experimental drug; 5. Pregnant or unwilling to use reliable contraception (fertile women will have a pregnancy test prior to randomization); 6. Major psychiatric disorder; 7. Diseases and medications that affect glucose tolerance (e.g. pheochromocytoma, Cushing’s syndrome, acromegaly, steroid-dependent asthma, protease inhibitors, antipsychotics); 8. Unwillingness to be randomized or sign informed consent); 9. Known uncontrolled substance abuse; 10. Inability to understand study information and/or communicate with clinic staff.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare beta-cell function, as reflected by the first phase insulin secretion corrected for insulin sensitivity and/or the arginine-stimulated insulin secretion, both co-primary endpoints as measured during the eu-hyperglycemic clamp procedure, following 52 weeks of rosiglitazone, valsartan or rosiglitazone combined with valsartan in subjects with IFG (with and without a family history of DM2) and/or IGT. Amendment 2007: To compare beta-cell function, as reflected by the first phase insulin secretion corrected for insulin sensitivity and/or the arginine-stimulated insulin secretion, both co-primary endpoints as measured during the eu-hyperglycemic clamp procedure, following 26 weeks of valsartan in subjects with IFG (with and without a family history of DM2) and/or IGT | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare the effects of 52 weeks of rosiglitazone, valsartan or rosiglitazone combined with valsartan in subjects with IFG (with and without a family history of DM2) and/or IGT with respect to: 1. Fasting plasma glucose; 2. Second phase insulin secretion in response to hyperglycemia during the hyperglycemic clamp test; 3. All the above-mentioned beta-cell function parameters at 12 weeks after discontinuation of therapy to assess durability/disease modifying effects; 4. The conversion from normal glucose tolerance (NGT) to IGT or diabetes (as evaluated by an oral glucose tolerance test); 5. HbA1c, fasting blood glucose and lipid/lipoprotein concentrations; 6. Insulin sensitivity assessed during the euglycemic clamp test; 7. Safety and tolerability, including assessments of hypoglycemic events, blood pressure, and urinary albumin excretion rate. Amendment 2007: To compare the effects of 26 weeks of valsartan in subjects with IFG (with and without a family history of DM2) and/or IGT with respect to: 1. Fasting plasma glucose; 2. Second phase insulin secretion in response to hyperglycemia during the hyperglycemic clamp test; 3. HbA1c, fasting blood glucose and lipid/lipoprotein concentrations; 4. Insulin sensitivity assessed during the euglycemic clamp test; 5. Safety and tolerability. | — |
Contacts
Public ContactM. Diamant
VU University Medical Center, Department of Endocrinology, Diabetescenter, De Boelelaan 1117, P.O. Box 7057
Outcome results
None listed