Clinical trial NCT00282178: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Obesity
Keywords: Metabolic
Hypertension
Abdominal obesity
Insulin sensitivity
Hyperinsulinemic euglycemic clamp
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: Sahlgrenska University Hospital
name: AstraZeneca
First posted: 2006-01-25
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Compare the effect of candesartan and hydorclorothiszide treatment on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp
timeFrame: 12 weeks
Secondary outcomes:
measure: Compare the effect of candesartan treatment with placebo on insulin sensitivity and compared with hydrochlorothiazide and placebo on:
timeFrame: 12 weeks
measure: beta cell function
timeFrame: 12 weeks
measure: vascular/endothelial function;
timeFrame: 12 weeks
measure: lipolysis regulation
timeFrame: 12 weeks
measure: autonomic nerve activity;
timeFrame: 12 weeks
measure: abdominal fat tissue distribution;
timeFrame: 12 weeks
measure: amount of lean body and fat mass;
timeFrame: 12 weeks
measure: liver and muscle fat;
timeFrame: 12 weeks
measure: interaction betw. insulin and AT-II in fat cell metabolism; fat cell gene expression
timeFrame: 12 weeks
measure: adipokine levels
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Umeå
country: Sweden
facility: Umeå University Hospital
Study officials:
affiliation: Dept of Medicine, Umeå University Hospital, Sweden
name: Jan Eriksson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: