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| Name | Class |
|---|---|
| Organon | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Testosterone | Experimental | oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks |
|
| Placebo | Placebo Comparator | identical to active medication, taken in an identical way to the active arm |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Testosterone undecanoate | Drug | Licensed for androgen deficiency |
|
| Measure | Description | Time Frame |
|---|---|---|
| Myocardial Perfusion | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial Function | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter Collins, MA MD FRCP | Imperial College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Brompton & Harefield NHS Trust | London | SW3 6NP | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18308009 | Result | 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. |
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Blood was taken at a screening visit. Those not fulfulling the inclusion/exclusion criterial were excluded.
Outpatients at a tertiary referral NHS hospital in London, UK. Eligible patients were invited to participate by post. Interested participants returned an eligibility questionnaire. Those fulfilling the inclusion/exclusion criteria were invited to attend for a screening/consent appointment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Testosterone (First, Then Placebo) | oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks. At the end of 8 weeks, patients were evaluated, then crossed-over to placebo for 8 weeks. No wash-out period. Testosterone undecanoate: Licensed for androgen deficiency |
| FG001 | Placebo (First, Then Testosterone) | identical to active medication, taken in an identical way to the active arm for 8 weeks. At the end of the 8 week placebo treatment phase evaluation visit, patients crossed-over to the testosterone treatment arm for 8 weeks. No wash-out period. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Randomized |
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| |||||||||||||||||||||
| Started Intervention After Randomization |
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| Completed Study Protocol |
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28 participants were randomized to testosterone or placebo first then crossed over after 8 weeks, and 25 patients completed the study protocol. There was no carry-over effect detected from the first to the second period, therefore the data presented here are pooled data of both treatment arms.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | All participants randomized to study medication (n=28), whether randomized to testosterone or placebo first. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Myocardial Perfusion | 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. | 22 patients had assessable CMR data for both evaluation visits. | Posted | Mean | Standard Deviation | myocardial perfusion index | Testosterone versus placebo (8 week treatment period) |
|
Event data were collected from time of participant inclusion in the study until the end of the final study visit (end of the second treatment phase and assessment visit) - a total of approximately 20 weeks. There was no formal long-term follow-up.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Testosterone | oral testosterone undecanoate, 80mg twice daily (Andriol Testocaps, Organon, The Netherlands) for 8 weeks Testosterone undecanoate: Licensed for androgen deficiency Active and placebo given in a cross-over design |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hospitalization | Nervous system disorders | Non-systematic Assessment | Suspected stroke and pneumonia approximately 2 weeks after starting study medication (active arm). Serious adverse event (SAE) not considered to be related to study medication. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Low mood | Nervous system disorders | Non-systematic Assessment | Patient complained of general malaise and feeling of exhaustion, 'almost a depression' and stopped the study medication (placebo). He decided to withdraw from the study. These symptoms resolved after 2 weeks off the study medication. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Carolyn Webb | Imperial College London | 03301288860 | c.webb@imperial.ac.uk |
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| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C010792 | testosterone undecanoate |
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Pharmacy dispensing of study medication that was randomized by supplier
| Testosterone versus placebo (8 week treatment period) |
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| NOT COMPLETED |
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| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | pooled first and second treatment phase data |
|
|
| Secondary | Endothelial Function | 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. | A total of 17 patients had endothelial function assessments - the same patients took both interventions in a randomized cross-over design. | Posted | Mean | Standard Deviation | Augmentation index | Testosterone versus placebo (8 week treatment period) |
|
|
|
| 0 |
| 28 |
| 1 |
| 28 |
| 0 |
| 28 |
| EG001 | Placebo | identical to active medication, taken in an identical way to the active arm | 0 | 28 | 0 | 28 | 1 | 28 |
|
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