Testosterone Therapy on Angina Threshold and Atheroma in Patients With Chronic Stable Angina

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2006 by Sheffield Teaching Hospitals NHS Foundation Trust.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00131183
First received: August 15, 2005
Last updated: September 11, 2006
Last verified: September 2006
  Purpose

This study aims to address the following questions on the effects of testosterone therapy in men with coronary ischaemia:

  • Does the anti-anginal effect persist long term? Many of the published studies are acute single dose trials and none of the chronic studies have assessed patients formally beyond a few months. The investigators' earlier studies were limited to 3 months.
  • Does testosterone therapy in men affect the levels of measurable atheroma? There is currently no in-vivo human evidence that androgen therapy inhibits or reduces levels of atheroma, although there is abundant evidence in animals to suggest a potential improvement.

This study addresses the two issues and would be of one-year duration but would be the longest trial of testosterone therapy in men with cardiovascular disease. The primary endpoint is the change in time to ST- segment depression of > 1mm during exercise testing.


Condition Intervention Phase
Angina Pectoris
Drug: Nebido
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Effect of Testosterone Therapy on Angina Threshold and Atheroma in Patients With Chronic Stable Angina

Resource links provided by NLM:


Further study details as provided by Sheffield Teaching Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Change in time to ST- segment depression of > 1mm during exercise testing

Secondary Outcome Measures:
  • Change in carotid atheroma assessed by media:intimal thickness ratio of the carotid artery
  • Change in time to exercise induced chest pain as judged by a single observer
  • Change in frequency of attacks of angina as recorded in the patients’ angina diary
  • Change in high sensitivity C reactive protein (hs-CRP)
  • Change in scores on the Seattle Angina Questionnaire (SAQ)
  • Change in scores of quality of life (Euroquol)
  • Change in scores of depression using the Beck Depression Inventory

Estimated Enrollment: 80
Study Start Date: September 2005
Detailed Description:

In the past 4 years the investigators' research group has completed 2 studies on the effect of testosterone therapy on exercise induced coronary ischaemia (clinically manifest as angina pectoris). We, the investigators at Sheffield Teaching Hospitals, have shown that testosterone replacement therapy improved exercise duration on the treadmill and prolonged time to ischaemia (ischaemic threshold). Moreover, we demonstrated a dose response relationship between the increase in exercise duration and the baseline testosterone level so that men with lower baseline testosterone level derived the greatest symptomatic benefit from replacement therapy. Importantly we have also demonstrated that the effects of testosterone are maintained in the presence of concomitant anti-anginal drug therapy and at physiological levels of testosterone therapy. (English et al. 2000; Malkin 2004)

Furthermore we have found the prevalence of men with coronary disease and low serum testosterone levels to be approximately 25%. This represents a large population of men with low testosterone levels that may benefit symptomatically from testosterone therapy. These men qualify for androgen replacement therapy per se simply to relieve hypogonadal symptoms and maintain bone mineral density and there are clinical guidelines recommending physiological testosterone replacement in this cohort. (Morales and Lunenfeld 2002) The safety issues relating to testosterone treatment which comprise a theoretical increased risk of prostate neoplasia and increased erythropoiesis are of limited relevance in this population because replacement therapy only returns the testosterone level to the physiological range. Indeed, there is no evidence that appropriate testosterone therapy increases the risk of prostate cancer. More importantly, prostate cancer can be identified early by screening for prostate specific antigen allowing careful surveillance during replacement therapy.

This study aims to address the following questions on the effects of testosterone therapy in men with coronary ischaemia:

  • Does the anti-anginal effect persist long term? Many of the published studies are acute single dose trials and none of the chronic studies have assessed patients formally beyond a few months. Our earlier studies were limited to 3 months.
  • Does testosterone therapy in men affect the levels of measurable atheroma? There is currently no in-vivo human evidence that androgen therapy inhibits or reduces levels of atheroma, although there is abundant evidence in animals to suggest a potential improvement.

This study addresses the two issues and would be of one-year duration but would be the longest trial of testosterone therapy in men with cardiovascular disease.

The primary endpoint is change in time to ST- segment depression of > 1mm during exercise testing.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males over 20 years of age
  • Stable, chronic angina pectoris for > 1 month
  • ST- segment depression of > 1mm within 12 minutes of the Bruce protocol
  • Willing and able to give informed consent and comply with the study protocol
  • Serum testosterone (< 12nmol/L)

Exclusion Criteria:

  • Use of androgen therapy or anabolic steroids within 6 months of entry into the study (i.e. screening visit/visit 1) or concurrent use of androgens including dehydroepiandrosterone (DHEA), anabolic steroids, clomipramine, antiandrogens, estrogen, cytochrome P450 inducing medicines (e.g. quinidine, ketoconazole, macrolides), corticotrophins (ACTH), oxyphenbutazone
  • Contraindication to treatment with Nebido®.
  • Organic hypothalamic-pituitary pathology
  • Prostate specific antigen (PSA) >= 4ng/ml
  • Severe symptomatic benign prostatic hyperplasia
  • Patients actively or potentially trying to start a family or requiring fertility treatment
  • Suspicion of, current, or past history of breast or prostatic carcinoma
  • Myocardial infarction (MI), coronary artery bypass graft surgery (CABG) or percutaneous transluminal coronary angioplasty (PTCA) in the last three months.
  • Significant hepatic, respiratory, haematological or renal disease
  • Haematocrit > 50% at entry to the study (i.e. screening visit/visit 1)
  • History of significant arrhythmia, Wolff-Parkinson-White (WPW) syndrome, > 1st degree heart block, or cerebrovascular accident (CVA) within the last three months
  • History of drug or alcohol abuse
  • Receiving other trial drugs within 12 weeks
  • Hypotension (systolic blood pressure [BP] < 100 mm Hg)
  • Severe, malignant, complicated, renovascular, secondary, or uncontrolled hypertension (BP > 180/114)
  • Hypercalcaemia
  • Nephrotic range proteinuria
  • Symptomatic obstructive sleep apnoea syndrome
  • Electrocardiogram (ECG) abnormalities that preclude ST- segment analysis (eg left bundle branch block [LBBB], atrial fibrillation [AF])
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131183

Contacts
Contact: Kevin S Channer, MBChB (Hons) 0114 2713473 kevin.channer@sth.nhs.uk

Locations
United Kingdom
Royal Hallamshire Hospital Recruiting
Sheffield, South Yorkshire, United Kingdom, S10 2JF
Contact: Kevin S Channer, MBChB (Hons)    0114 2713473    kevin.channer@sth.nhs.uk   
Principal Investigator: Kevin S Channer, MBChB (Hons)         
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Kevin S Channer, MBChB (Hons) Sheffield Teaching Hospitals NHS Foundation Trust
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00131183     History of Changes
Other Study ID Numbers: STH13979
Study First Received: August 15, 2005
Last Updated: September 11, 2006
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
Angina Pectoris
Arteriosclerosis
Testosterone

Additional relevant MeSH terms:
Angina Pectoris
Plaque, Atherosclerotic
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Pathological Conditions, Anatomical
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on July 20, 2014