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

Sponsor:	Umeå University
Collaborators:	Sahlgrenska University Hospital, Sweden AstraZeneca
Information provided by:	Umeå University
ClinicalTrials.gov Identifier:	NCT00282178

Purpose

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.

Condition	Intervention	Phase
Hypertension Obesity	Drug: Hydrochlorothiazide Drug: Placebo Drug: Candesartan	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized, Control: Active Control, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Official Title:	A 36 Week Three-Center Double-Blind Randomized Cross-Over Trial Comparing Metabolic Effects of Candesartan, Hydrochlorothiazide and Placebo

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure Obesity

Drug Information available for: Hydrochlorothiazide CV 11974 Candesartan cilexetil

U.S. FDA Resources

Further study details as provided by Umeå University:

Primary Outcome Measures:

Compare the effect of candesartan and hydorclorothiszide treatment on insulin sensitivity assessed with hyperinsulinemic euglycemic clamp [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Compare the effect of candesartan treatment with placebo on insulin sensitivity and compared with hydrochlorothiazide and placebo on: [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
beta cell function [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
vascular/endothelial function; [ Time Frame: 12 weeks ]
lipolysis regulation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
autonomic nerve activity; [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
abdominal fat tissue distribution; [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
amount of lean body and fat mass; [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
liver and muscle fat; [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
interaction betw. insulin and AT-II in fat cell metabolism; fat cell gene expression [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
adipokine levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment:	26
Study Start Date:	April 2005
Study Completion Date:	April 2006
Primary Completion Date:	March 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Candesartan 16-32 mg once daily	Drug: Candesartan 16-32 mg once daily 12 weeks
2: Active Comparator Hydrochlorothiazide 25-50 mg once daily	Drug: Hydrochlorothiazide 25-50 mg once daily
3: Placebo Comparator	Drug: Placebo Once daily

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

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00282178

Locations

Sweden
Umeå University Hospital
Umeå, Sweden, SE-90185

Sponsors and Collaborators

Umeå University

Sahlgrenska University Hospital, Sweden

AstraZeneca

Investigators

Principal Investigator:

Jan Eriksson, MD, PhD

Dept of Medicine, Umeå University Hospital, Sweden

More Information

No publications provided

Responsible Party:	Umeå University Hospital ( Jan Eriksson )
Study ID Numbers:	D2452L00007
Study First Received:	January 24, 2006
Last Updated:	October 15, 2008
ClinicalTrials.gov Identifier:	NCT00282178 History of Changes
Health Authority:	Sweden: Medical Products Agency

Keywords provided by Umeå University:

Metabolic
Hypertension
Abdominal obesity
Insulin sensitivity
Hyperinsulinemic euglycemic clamp

Additional relevant MeSH terms:

Obesity
Molecular Mechanisms of Pharmacological Action
Sodium Chloride Symporter Inhibitors
Physiological Effects of Drugs
Diuretics
Vascular Diseases
Overweight
Cardiovascular Agents
Antihypertensive Agents
Hydrochlorothiazide
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers

Membrane Transport Modulators
Body Weight
Candesartan cilexetil
Signs and Symptoms
Natriuretic Agents
Therapeutic Uses
Candesartan
Nutrition Disorders
Cardiovascular Diseases
Overnutrition
Hypertension

ClinicalTrials.gov processed this record on March 18, 2010