Testosterone and Myocardial Perfusion in CHD

Condition(s) targeted: Coronary Heart Disease

Intervention: Testosterone undecanoate (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Imperial College London

Official(s) and/or principal investigator(s):
Peter Collins, MA MD FRCP, Principal Investigator, Affiliation: Imperial College London

Testosterone has traditionally been regarded as a risk factor for heart disease due to the fact that males have a higher incidence of this disease than women, at least until the menopause. However recent studies have shown that men with low levels of testosterone may be at an increased risk of developing coronary heart disease (furring up of the blood vessels supplying blood to the heart). Our group has demonstrated a relaxing effect of testosterone in isolated animal coronary arteries (blood vessels supplying blood to the heart). We have shown that short-term testosterone administration can increase coronary artery and brachial artery (blood vessel in the arm) blood flow and can decrease the lack of blood supply to the heart muscle in men with coronary artery disease. These findings indicate a need for similar but longer-term studies to investigate the possible beneficial effects of longer-term testosterone therapy on the heart and blood vessels. Should this treatment be shown to be beneficial to men with coronary artery disease it may be a useful additional therapy for men with the furring up of arteries in the heart and the resulting angina.

Aim To investigate our hypothesis that testosterone can beneficially affect myocardial perfusion, vascular reactivity, metabolic risk factors for coronary heart disease and improve quality of life in men with low plasma testosterone levels and coronary heart disease.

Official title: Effects of Chronic Testosterone on Myocardial Ischaemia and Endothelial Function in Men With Documented Coronary Heart Disease

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Bio-equivalence Study

Primary outcome: Myocardial perfusion measured using Cardiovascular Magnetic Resonance (CMR)

Detailed description: The main purpose of this project is to determine whether testosterone treatment over a number of weeks can beneficially affect myocardial perfusion, vascular reactivity, metabolic risk factors and quality of life in men with documented coronary heart disease. Men with documented significant coronary artery disease and a positive exercise test for myocardial ischaemia will be enrolled into the study. They will be randomised to active testosterone therapy (5 mg/day) or placebo for 2 months. After 2 months they will undergo MRI perfusion scanning, radial artery applanation tonometry to assess endothelial function, blood sampling for analysis of metabolic risk factors for coronary heart disease, complete quality of life questionnaires and will cross-over to the opposite treatment. After a further 2 month period these tests will be repeated. Angina diaries will be kept for the duration of the study.

Minimum age: 35 Years. Maximum age: 75 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Men

- Aged 35 to 75 years

- Angiographically proven coronary artery disease (70 lesion in at least one major coronary artery, or major branch), including patients post-CABG and PTCA

- Plasma testosterone less than or equal to 12 nmol/l

- Normal prostate specific antigen (PSA; normal range 0 – 4 g/l)

- Willing to give written informed consent

Exclusion Criteria:

- Significant arrhythmia, particularly those which would affect interpretation of the ST-segment of the ECG

- Treatment with digitalis

- Treatment with testosterone or similar hormonal therapy

- Thoracic or abdominal surgery within the previous 3 months

- Haemoglobin >16 g/dL

- Haematocrit >50%

- History of hormone-dependent cancer such as prostate or breast cancer

- Hypercalcaemia

- Nephrosis

- Pacemaker or AICD

- Implanted ferromagnetic arterial clips

- Left ventricular hypertrophy

- NYHA III or IV

- Intolerance of confined spaces

- Previous allergic reaction to Gadolinium

- Participation in another research study within the previous 60 days

- Unwilling to give written informed consent

Royal Brompton & Harefield NHS Trust, London SW3 6NP, United Kingdom

Starting date: June 2001
Ending date: April 2004
Last updated: October 13, 2005