Double-Blind Randomized Cross-Over Trial Comparing Metabolic Effects of Candesartan, Hydrochlorothiazide and Placebo

Official Title: “A 36 Week Three-Center Double-Blind Randomized Cross-Over Trial Comparing Metabolic Effects of Candesartan, Hydrochlorothiazide and Placebo”

The purpose of this study is to investigate the effect of a 12-week candesartan treatment compared with hydrochlorothiazide on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp.

To investigate the mechanisms underlaying the diabetes-preventing effect of candesartan with respect to possible impact on insulin sensitivity, beta cell function and adipose tissue function and distribution. For this purpose comparisons will be performed with hydrochlorothiazide and placebo treatment. It is hypothesized that candesartan will improve insulin sensitivity as compared to hydrochlorothiazide and possibly also in comparison with placebo and that this could be explained by altered fat tissue function or distribution or by an altered sympathetic to parasympathetic balance in the autonomic nervous system.

Hydrochlorthiazide is chosen as comparator because thiazides are a recommended firs-line therapy in hypertension. This drug class has some detrimental effects on glucose tolerance and in insulin sensitivity.

Intervention(s) in this Clinical Trial

• Drug: Hydrochlorothiazide
  • 25-50 mg once daily
• Drug: Placebo
  • Once daily
• Drug: Candesartan
  • 16-32 mg once daily 12 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Candesartan 16-32 mg once daily
• Active Comparator: 2
  • Hydrochlorothiazide 25-50 mg once daily
• Placebo Comparator: 3

Primary Measures

• Compare the effect of candesartan and hydorclorothiszide treatment on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• Compare the effect of candesartan treatment with placebo on insulin sensitivity and compared with hydrochlorothiazide and placebo on:
  • Time Frame: 12 weeks
    Safety Issue?: No
• beta cell function
  • Time Frame: 12 weeks
    Safety Issue?: No
• vascular/endothelial function;
  • Time Frame: 12 weeks
    
• lipolysis regulation
  • Time Frame: 12 weeks
    Safety Issue?: No
• autonomic nerve activity;
  • Time Frame: 12 weeks
    Safety Issue?: No
• abdominal fat tissue distribution;
  • Time Frame: 12 weeks
    Safety Issue?: No
• amount of lean body and fat mass;
  • Time Frame: 12 weeks
    Safety Issue?: No
• liver and muscle fat;
  • Time Frame: 12 weeks
    Safety Issue?: No
• interaction betw. insulin and AT-II in fat cell metabolism; fat cell gene expression
  • Time Frame: 12 weeks
    Safety Issue?: No
• adipokine levels
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Male and female 18-70 years old
• Diagnosed hypertension and abdominal obesity (waist circumference greater than or equal to 102 cm (M) or 88 cm (F)

Exclusion Criteria:

• Uncontrolled hypertension
• Treatment with more than two concomitant antihypertensive medications
• Diabetes Mellitus
• Other endocrine disorder
• Severe liver disease
• Severely reduced renal function
• Malignant disease
• Alcohol or drug abuse
• Severe psychiatric illness
• History of stroke, myocardial infarction, unstable angina pectoris, participation in another clinical trial less than two months prior to screening visit
• treatment with anti-obesity drugs
• anti-inflammatory drugs or immunosuppressive drugs

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Umeå University Other

Overall Clinical Trial Officials and Contacts

Jan Eriksson, MD, PhD Principal Investigator Dept of Medicine, Umeå University Hospital, Sweden  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00282178

Study ID Number: D2452L00007

ClinicalTrials.gov Identifier: NCT00282178

Health Authority: Sweden: Medical Products Agency