Effect of Folic Acid on Endothelial and Baroreceptor Function in Patients With Heart Failure

October 1, 2007 updated by: University of Zurich

The randomized, double-blind, placebo-controlled study aim to evaluate the effect of 1-month therapy with folic acid (5 mg/day) on endothelial function and baroreceptor function in patients with heart failure.

Endothelial function will be studied non-invasively with flow-mediated dilation while for eveluating baroreceptor function sympathetic nervous system activity will be measured directly with microneurography in baseline condition and during infusion of sodium-nitroprusside.

Study Overview

Status

Terminated

Conditions

Heart Failure

Intervention / Treatment

Drug: folic acid 5mg/day

Detailed Description

Endothelial and baroreceptor function are impaired in patients with heart failure.

Impaired baroreflex control of the heart and peripheral circulation and endothelial dysfunction are thought to play an important pathophysiological role in chronic heart failure and confers a poor prognosis.

In patients with essential hypertension we demonstrated an improvement in baroreceptor function after treatment with folic acid.

Therefore, the aim of the present randomized, double-blind, placebo-controlled study was to evaluate endothelial function and baroreceptor function in patients with heart failure before and after 1-month therapy with folic acid (5 mg) or placebo.

Endothelial function will be assessed with novel high-resolution ultrasound devices, which allows to investigate endothelial function in vivo. This method makes use of the property of the endothelium to release nitric oxide in response to shear stress and increased flow as previously described. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent glycerol trinitrate (GTN) (0.4 mg sublingual, Nitrolingual Spray, Pohl-Boskamp, Germany)-induced vasodilation of the brachial artery will be assessed by a high-resolution ultrasound vessel wall tracking device with a 10 MHz linear array transducer . FMD of the brachial artery is induced by release of a wrist cuff inflated 50 mmHg above systolic pressure for 5 minutes. After sublingual GTN application, used as endothelium-independent stimulus, the diameter will be recorded every 30 seconds for 6 minutes.

Multifiber recordings of muscle sympathetic nerve activity will be obtained from the peroneal nerve posterior to the fibular head with tungsten microelectrodes. The sympathetic nervous activity will be measured continuously together with ECG, respiration rate and blood pressure. Baroreceptor modulation of muscle sympathetic nerve activity and heart rate would be assessed by intravenous infusion of sodium nitroprusside.

Study Type

Interventional

Phase

Phase 4

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

Heart failure (min. NYHA ll, LVEF <50%)
Not smokers
Written informed consent

Exclusion Criteria:

Unstable heart failure
Smoking
Unstabile Angina Pectoris
Endocrinologic disease such as Diabetes mellitus, Hypo- und Hyperthyroidism
Alcohol abuse
Epilepsia
Treatment with folic acid antaponists Trimethoprim, Pyrimethamin, Methotrexat..
Participation to one other clinical Study within 1 Month

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
change in endothelial function Time Frame: 1 month	1 month
change in baroreceptor function Time Frame: 1 month	1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Zurich

Investigators

Principal Investigator: Georg Noll, MD, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2004

Study Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

June 25, 2007

First Submitted That Met QC Criteria