Effect of Irbesartan on Insulin Sensitivity in Chronic Heart Failure

Chronic Heart Failure Clinical Trial

Official title:

Effect of the Angiotensin II Receptor Antagonist Irbesartan on Insulin Sensitivity and Metabolic Profile in Patients With Chronic Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00347087
• Other study ID #: IRIS HF 7/04
• Status: Completed
• Phase: Phase 4
• First received: June 29, 2006
• Last updated: October 30, 2007
• Start date: July 2004
• Est. completion date: June 2007

Study information

• Verified date: October 2007
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

To test whether treatment with the angiotensin II receptor antagonist Irbesartan improves insulin sensitivity and metabolic profile in patients with chronic heart failure.

Description:

In CHF impaired insulin sensitivity is a common finding characterised by elevated fasting insulin levels and impaired effectiveness of insulin to utilise glucose in peripheral tissues, mainly in skeletal muscle tissue. Additionally, impaired insulin sensitivity, i.e. insulin resistance, progresses in parallel to severity of CHF and relates to major clinical symptoms such as reduced exercise capacity and muscle fatigue. In survival analyses, insulin resistance is a significant predictor of mortality, independently of and additionally to other established prognostic markers such as age, NYHA class, peak oxygen consumption, or LVEF. These findings indicate that insulin resistance is involved in CHF pathophysiology. Importantly, insulin resistance in CHF occurs independently of ischemic etiology. In ischaemic heart disease, however, insulin resistance as part of the metabolic syndrome is also an important prerequisite for the development of arteriosclerosis. Accordingly insulin resistance was found worst in CHF patients with ischemic etiology compared to patients with CHF due to dilated cardiomyopathy and those with ischaemic heart disease without heart failure. On the basis of these findings we hypothesise that therapeutically improving insulin sensitivity may have additional beneficial effects on energy utilisation and therefore improve clinical symptoms such as reduced exercise capacity and muscle fatigue.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. ambulatory patients with symptomatic chronic heart failure (NAHY II-IV)

2. ischemic etiology

3. LVEF = 45%

4. standard medical treatment for CHF (such as diuretics, beta blockers, ACE inhibitors, aspirin or warfarin). Patients should be treated with ACI inhibitor for at least 12 months prior to enrolment into the study. Patients should not be treated with angiotensin II receptor antagonists during the study other than the trial medication. Further medical treatment such as spironolactone, amiodarone and others are allowed if the patient is on a stable dose at the beginning of the trial. Dosages should be kept stable during the trial except adjustment is judged necessary for clinical reason.

5. Patient should be hospitalised due to deterioration of the cardiac disease at least once in the last 12 months under ACE-I therapy.

6. age > 21 years

7. informed consent

Exclusion Criteria:

1. hospitalisation with intervention within 2 weeks of intended randomisation

2. unstable IHD or Myocardial infarction < 2 months

3. open diagnosed diabetes mellitus / antidiabetic treatment with insulin, metformin, sulfonylurea, glinides

4. COPD treated with steroids

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure
• Insulin Resistance

Intervention

Drug:
• Irbesartan
up-titration over 4 weeks to target dose 300 mg od

Locations

Country	Name	City	State
Germany	Applied Cachexia Research, Cardiology Dept. Charite Medical School, Virchow Klinikum	Berlin

Sponsors (2)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	Bristol-Myers Squibb

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity assessment using intravenous glucose tolerance testing		3 months
Secondary	Assessment of body composition using dual energy x-ray absorptiometry		3 months
Secondary	Assessment of exercise capacity on a treadmill including respiratory gas analysis		3 months