Clinical trial NCT00239590: Testosterone and Myocardial Perfusion in Coronary Heart Disease (CHD)
Official title: Effects of Chronic Testosterone on Myocardial Ischaemia and Endothelial Function in Men With Documented Coronary Heart Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Heart Disease
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Organon
First posted: 2005-10-17
Enrollment: 28
Sex: MALE
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* Men
* Aged 35 to 75 years
* Angiographically proven coronary artery disease (70 percent lesion in at least one major coronary artery, or major branch), including patients post-coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI)
* 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 percent
* History of hormone-dependent cancer such as prostate or breast cancer
* Hypercalcaemia
* Nephrosis
* Pacemaker or automated implantable cardiac defibrillator
* Implanted ferromagnetic arterial clips
* Left ventricular hypertrophy
* New York Heart Association (NYHA) III or IV functional class
* 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

Primary outcomes:
measure: Myocardial Perfusion
timeFrame: Testosterone versus placebo (8 week treatment period)
Secondary outcomes:
measure: Endothelial Function
timeFrame: Testosterone versus placebo (8 week treatment period)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Brompton & Harefield NHS Trust
Study officials:
affiliation: Imperial College London
name: Peter Collins, MA MD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Webb CM, Elkington AG, Kraidly MM, Keenan N, Pennell DJ, Collins P. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease. Am J Cardiol. 2008 Mar 1;101(5):618-24. doi: 10.1016/j.amjcard.2007.09.114. Epub 2007 Dec 21.