Effect of Testosterone on Endothelial Function and Microcirculation in Type 2 Diabetic Patients With Hypogonadism

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Tameside Hospital NHS Foundation Trust
Sponsor:
Information provided by (Responsible Party):
Dr Edward Jude, Tameside Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01084369
First received: March 9, 2010
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

Diabetes mellitus is associated with long-term complications affecting mainly the eyes, nerves and kidneys. One of the main underlying causes for this is damage to the lining of the small blood vessels supplying these organs with dysfunction of the endothelium (lining of the small blood vessels). Testosterone has been shown to have an effect macro (large) blood vessels with limited data available on the micro (small) blood vessels. Testosterone is recognised to have important effects on metabolism and vascular behaviour beyond the accepted effects on secondary sexual characteristics. Physiological testosterone therapy is associated with some beneficial effects on the cardiovascular system and has been used with some success to treat patients with stable angina and chronic heart failure. The investigators therefore propose to study the effects of testosterone replacement therapy in patients with hypogonadism (low testosterone levels) on the endothelium in males with type 2 diabetes. 40 diabetic patients with type 2 diabetes and low testosterone levels and erectile dysfunction (impotence) will be recruited into the study. All patients will receive testosterone replacement therapy and 10 patients will also receive Vardenafil (a drug used to treat impotence). The investigators hope to demonstrate an improvement in endothelial dysfunction by assessing biochemical markers such as nitric oxide (a chemical that causes relaxation for the blood vessels) and C-reactive protein (a chemical that can increase in patients with diabetes) as well as the effect on weight, blood pressure, diabetes control and cholesterol.


Condition Intervention Phase
Type 2 Diabetes
Hypogonadism
Drug: Testosterone
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IV: Effect of Testosterone on Endothelial Function and Microcirculation in Type 2 Diabetic Patients With Hypogonadism

Resource links provided by NLM:


Further study details as provided by Tameside Hospital NHS Foundation Trust:

Primary Outcome Measures:
  • Improvement in endothelial dependent and endothelial-independent vasodilatation [ Time Frame: 30 and 54 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Markers of endothelial function [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]

    Secondary efficacy variables will include changes of the following

    • Availability of nitric oxide
    • Endothelial inflammation as measured by CRP
    • Serum levels of endothelial markers: IGF and adhesion molecules
    • BMI, waist circumference, glycaemic control (HbA1c), lipid profile and blood pressure.
    • Other laboratory parameters


Estimated Enrollment: 40
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Testosterone, Vardenafil
All patients will receive Testosterone (n=40) of these (10 patients) will also receive Vardenafil
Drug: Testosterone

NEBIDO ampoules containing a solution for injection of 1000mg/4ml of testosterone undecanoate. NEBIDO injection 1000mg/4ml will be given at baseline, 6 weeks, 18 weeks, 30 weeks, 42 and 54 weeks. Levitra will be given to those patients with erectile dysfunction for 2 weeks in addition to Nebido.

Concomitant medication deemed necessary by the investigator as part of the routine clinical management will be permissable.

Other Names:
  • Testosterone (NEBIDO)
  • Vardenafil (Levitra)

  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 40 male patients with type 2 diabetes mellitus.
  • T2DM as judged by WHO criteria:

    • onset of diabetes mellitus after the age of 30 years
    • blood glucose controlled by diet or drugs other than insulin, or insulin initiated after 2 years diagnosis of diabetes
    • no history of diabetic ketoacidosis.
  • Symptomatic Hypogonadism as defined by:

    • Total testosterone below 10 nmol/l
    • Aging males' symptom score (AMS) above 36.
  • Hypogonadic men with erectile dysfunction
  • Age range- 50-80 years

Exclusion Criteria:

  • Patients with uncontrolled hypertension (BP>145/95 on treatment) or significant hypotension. (BP<100 systolic)
  • Current smokers
  • Recent myocardial infarction (<6 months), unstable angina or ongoing chest pain, recent (within 6 months) cardiac intervention (e.g. angioplasty, stenting or CABG) or stroke.
  • Patients with clinical nephropathy (24 hr protein >0.5 g or urine protein +) or moderate renal failure (serum creatinine >150 micromol/l).
  • History of prostate cancer or suspicion of prostate cancer on clinical examination
  • Androgen dependent carcinoma of the male mammary gland
  • Liver tumours
  • Hypersensitivity to NEBIDO or LEVITRA
  • Polycythaemia
  • General systemic illness, including cardiac, renal or hepatic insufficiency
  • Patients on nitrates will not be included in the Levitra arm.
  • History of loss of vision in one eye because of non arteritic ischaemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure.
  • Hereditary degenerative retinal disorders such as retinitis pigmentosa.
  • Clinically significant chronic haematological disease which may lead to priapism
  • Bleeding disorders
  • Significant active peptic ulceration.
  • Concomitant use of vardenafil with HIV protease inhibitors such as ritonavir and indinavir is contraindicated, as they are potent inhibitors of CYP 3A4
  • Concomitant use of vardenafil with potent CYP 3A4 inhibitors ketoconazole and itraconazole (oral form) is contra-indicated in men older than 75 years.
  • Patients deemed unable to comply with the requirements of the protocol.
  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: NCT01084369

Contacts
Contact: Edward Jude, MD, MRCP 01619226964 edward.jude@tgh.nhs.uk

Locations
United Kingdom
Tameside General Hospital Recruiting
Ashton-under-Lyne, Lancashire, United Kingdom, OL6 9RW
Tameside Hospital NHS Foundatoin Trust Recruiting
Ashton under Lyne, United Kingdom, OL69RW
Sponsors and Collaborators
Tameside Hospital NHS Foundation Trust
Investigators
Principal Investigator: Edward Jude, MD, MRCP Tameside Hospital NHS Foundation Trust
  More Information

No publications provided

Responsible Party: Dr Edward Jude, Consultant Physician, Tameside Hospital NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01084369     History of Changes
Other Study ID Numbers: Testosterone version1
Study First Received: March 9, 2010
Last Updated: January 3, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Tameside Hospital NHS Foundation Trust:
Type 2 diabetes
Hypogonadism
Testosterone
Endothelial dysfunction

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Hypogonadism
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Gonadal Disorders
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Vardenafil
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Vasodilator Agents
Cardiovascular Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on September 18, 2014