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

Condition(s) targeted: Hypertension; Obesity

Intervention: Hydrochlorothiazide (Drug); Placebo (Drug); Candesartan (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Umeå University

Official(s) and/or principal investigator(s):
Jan Eriksson, MD, PhD, Principal Investigator, Affiliation: Dept of Medicine, Umeå University Hospital, Sweden

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Compare the effect of candesartan and hydorclorothiszide treatment on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp

Secondary outcome:

Compare the effect of candesartan treatment with placebo on insulin sensitivity and compared with hydrochlorothiazide and placebo on:

beta cell function

vascular/endothelial function;

lipolysis regulation

autonomic nerve activity;

abdominal fat tissue distribution;

amount of lean body and fat mass;

liver and muscle fat;

interaction betw. insulin and AT-II in fat cell metabolism; fat cell gene expression

adipokine levels

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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

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

Umeå University Hospital, Umeå SE-90185, Sweden

Starting date: April 2005
Last updated: October 15, 2008