Ursodeoxycholic Acid in Chronic Heart Failure

Condition(s) targeted: Heart Failure, Congestive

Intervention: Ursodeoxycholic Acid (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: National Heart and Lung Institute

Official(s) and/or principal investigator(s):
Philip A Poole-Wilson, MD, Principal Investigator, Affiliation: National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK

This is a double-blind, placebo-controlled, cross-over study evaluating the effects of UDCA on peripheral blood flow and immune function in patients with stable chronic heart failure (CHF). Sixteen patients with CHF will be recruited from the heart failure clinic at the Royal Brompton Hospital. Following baseline evaluation, patients will be randomised to receive either placebo or UDCA at a dose of 1000 mg/day for a period of four weeks. They will then undergo repeat evaluation (peripheral blood flow and immune function). A four week washout period will then take place before the patients cross-over to receive the respective other therapy for a further four weeks (i. e. those first receiving placebo will go onto receive UDCA and vice versa). The study will be completed after a total of twelve weeks, with a final assessment (peripheral blood flow and immune function).

Official title: Ursodeoxycholic Acid Therapy in Chronic Heart Failure: A Placebo-Controlled Study Evaluating the Effects of Ursodeoxycholic Acid on Peripheral Blood Flow and Immune Function

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome: peripheral blood flow as assessed by venous occlusion plethysmography

Secondary outcome:

- peak and resting arm and leg post-ischaemic blood flow as assessed by venous occlusion plethysmography

- Tumor Necrosis Factor-alpha (TNF), sCD14, soluble TNF-Receptor 1, Lipopolysaccharide levels

- cellular immune function

- Endothelin-1, B type natriuretic peptide, E-selectin plasma levels

Minimum age: 21 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- age >21 years

- of either sex

- the patient is willing and capable of complying with the requirements of this

protocol

- the patient has provided written informed consent

- the patient has clinical evidence of chronic heart failure:

1. reduced ejection fraction (≤40%) or left ventricular impairment on echocardiography (LVEDD ≥60mm)

2. stable clinical condition and medication for at least 1 month prior to the study (New York Heart Association class II-IV).

3. the patient is receiving appropriate conventional medical therapy for heart failure (ACE inhibitor or angiotensin II blocker, diuretics, beta-blocker as indicated and tolerated).

Exclusion Criteria:

- congenital heart disease

- any life-threatening disease, other than heart failure

- active malignancy of any type, or history of a malignancy within previous 5 years.

Patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years prior to study enrolment are acceptable.

- previous heart transplant

- severe neuro-muscular disease

- history of unstable angina, myocardial infarction or stroke within 3 months prior to

the study

- pregnancy or women of child-bearing age

- treatment with immunosuppressive therapy e. g. steroids for rheumatoid arthritis or

obstructive lung disease

- significant renal dysfunction (serum creatinine >250mmol/l), severe liver disease

(liver function tests > 3 times normal)

- unable to understand and comply with protocol or to give informed consent

National Heart and Lung Institute, London SW3 6LY, United Kingdom

Starting date: May 2004
Ending date: January 2006
Last updated: January 31, 2006