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

Phase 2

Completed

• Conditions: Hypertension; Obesity
• Interventions: Drug: Candesartan; Drug: Placebo; Drug: Hydrochlorothiazide

• Registration Number: NCT00282178
• Lead Sponsor: Umeå University

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2005-04
• Study First Submitted: 2006-01-24
• Study First Submitted QC: 2006-01-24
• Study First Posted: 2006-01-25
• Primary Completion: 2006-03
• Study Completion: 2006-04
• Status Verified: 2008-06
• Last Update Submitted: 2008-10-15
• Last Update Posted: 2008-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	Candesartan	Candesartan 16-32 mg once daily
3	Placebo	-
2	Hydrochlorothiazide	Hydrochlorothiazide 25-50 mg once daily

Primary Outcome Measures

Name	Time	Method
Compare the effect of candesartan and hydorclorothiszide treatment on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp	12 weeks

Secondary Outcome Measures

Name	Time	Method
Compare the effect of candesartan treatment with placebo on insulin sensitivity and compared with hydrochlorothiazide and placebo on:	12 weeks
beta cell function	12 weeks
vascular/endothelial function;	12 weeks
lipolysis regulation	12 weeks
autonomic nerve activity;	12 weeks
abdominal fat tissue distribution;	12 weeks
amount of lean body and fat mass;	12 weeks
liver and muscle fat;	12 weeks
interaction betw. insulin and AT-II in fat cell metabolism; fat cell gene expression	12 weeks
adipokine levels	12 weeks

Trial Locations

Locations (1)

Umeå University Hospital; 🇸🇪 Umeå, Sweden