Testosterone and Myocardial Perfusion in Coronary Heart Disease (CHD)

September 24, 2019 updated by: Imperial College London

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

28

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

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

35 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

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: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Testosterone
oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks
Drug: Testosterone undecanoate
Licensed for androgen deficiency
Other Names:
  • Andriol
  • Org 538
Placebo Comparator: Placebo
identical to active medication, taken in an identical way to the active arm
Drug: Testosterone undecanoate
Licensed for androgen deficiency
Other Names:
  • Andriol
  • Org 538

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial Perfusion
Time Frame: Testosterone versus placebo (8 week treatment period)

Myocardial perfusion (blood flow in the heart muscle) in subendocardial myocardial segments (one of the inner layers of heart muscle), supplied by coronary arteries without significant obstruction. This was measured using Cardiovascular Magnetic Resonance (CMR) imaging and a dual-bolus gadnolinium infusion protocol.

Myocardial perfusion index = the ratio between myocardial perfusion measurements following adenosine-induced stress and rest measurements.
Testosterone versus placebo (8 week treatment period)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial Function
Time Frame: Testosterone versus placebo (8 week treatment period)
The endothelium is a single layer of cells that line all blood vessels and regulates arterial function. Coronary artery disease causes dysfunction of the endothelium but some substances/drugs help to reverse this dysfunction. In this study, endothelial function was measured by radial applanation tonometry which measures the blood pressure waveform during each cardiac cycle (heart beat). Radial artery pulse recordings were acquired, with an averaged waveform generated from 20 sequential waveforms. Augmentation index (AIx) is derived from this averaged waveform, and is the ratio of the pulse pressure at the second systolic arterial pressure waveform peak to that of the first systolic peak. The change in AIx before and after salbutamol (400mcg) is a measure of endothelial function.
Testosterone versus placebo (8 week treatment period)

Collaborators and Investigators

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

Sponsor

Imperial College London

Collaborators

Organon

Investigators

  • Principal Investigator: Peter Collins, MA MD FRCP, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

June 1, 2001

Primary Completion (Actual)

April 24, 2004

Study Completion (Actual)

April 24, 2004

Study Registration Dates

First Submitted

October 13, 2005

First Submitted That Met QC Criteria

October 13, 2005

First Posted (Estimate)

October 17, 2005

Study Record Updates

Last Update Posted (Actual)

September 25, 2019

Last Update Submitted That Met QC Criteria

September 24, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2000AE13B

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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