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

Study Overview
=================
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.

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

Conditions
-----------------
Hypertension, Obesity

Intervention / Treatment
-----------------
* Drug: Hydrochlorothiazide
* Drug: Placebo
* Drug: Candesartan


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Candesartan 16-32 mg once daily | Drug: Candesartan<br>* 16-32 mg once daily 12 weeks<br>|
| Active Comparator: 2<br>Hydrochlorothiazide 25-50 mg once daily | Drug: Hydrochlorothiazide<br>* 25-50 mg once daily<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* Once daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the effect of candesartan and hydorclorothiszide treatment on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metabolic, Hypertension, Abdominal obesity, Insulin sensitivity, Hyperinsulinemic euglycemic clamp