Hypertension, Obesity
Conditions
Keywords
Metabolic, Hypertension, Abdominal obesity, Insulin sensitivity, Hyperinsulinemic euglycemic clamp
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.
Interventions
DRUGHydrochlorothiazide
25-50 mg once daily
DRUGPlacebo
Once daily
DRUGCandesartan
16-32 mg once daily 12 weeks
Sponsors
Sahlgrenska University Hospital
AstraZeneca
Umeå University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare the effect of candesartan and hydorclorothiszide treatment on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| beta cell function | 12 weeks |
| vascular/endothelial function; | 12 weeks |
| lipolysis regulation | 12 weeks |
| autonomic nerve activity; | 12 weeks |
| Compare the effect of candesartan treatment with placebo on insulin sensitivity and compared with hydrochlorothiazide and placebo on: | 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 |
| abdominal fat tissue distribution; | 12 weeks |
Countries
Sweden
Outcome results
None listed