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

This study has been completed.
Sponsor:
Collaborators:
Sahlgrenska University Hospital, Sweden
AstraZeneca
Information provided by:
Umeå University
ClinicalTrials.gov Identifier:
NCT00282178
First received: January 24, 2006
Last updated: October 15, 2008
Last verified: June 2008
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
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:


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
Active Comparator: 1
Candesartan 16-32 mg once daily
Drug: Candesartan
16-32 mg once daily 12 weeks
Active Comparator: 2
Hydrochlorothiazide 25-50 mg once daily
Drug: Hydrochlorothiazide
25-50 mg once daily
Placebo Comparator: 3 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: Jan Eriksson, Umeå University Hospital
ClinicalTrials.gov Identifier: NCT00282178     History of Changes
Other Study ID Numbers: D2452L00007
Study First Received: January 24, 2006
Last Updated: October 15, 2008
Health Authority: Sweden: Medical Products Agency

Keywords provided by Umeå University:
Metabolic
Hypertension
Abdominal obesity
Insulin sensitivity
Hyperinsulinemic euglycemic clamp

Additional relevant MeSH terms:
Hypertension
Obesity
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hydrochlorothiazide
Candesartan
Candesartan cilexetil
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on April 17, 2014