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

NCT01084369 | Terminated Phase 4

• 1 other identifier: Testosterone version1
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Type 2 Diabetes; Hypogonadism

Keywords

Type 2 diabetes; Hypogonadism; Testosterone; Endothelial dysfunction

Outcome Measures

Primary Outcomes (1)

• Improvement in endothelial dependent and endothelial-independent vasodilatation

  Improvement in markers of endothelial function

  30 and 54 weeks

Secondary Outcomes (1)

• Markers of endothelial function

  54 weeks

Study Arms (1)

Testosterone, Vardenafil

EXPERIMENTAL

All patients will receive Testosterone (n=40) of these (10 patients) will also receive Vardenafil

Drug: Testosterone

Interventions

Testosterone DRUG

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.

Also known as: Testosterone (NEBIDO), Vardenafil (Levitra)

Testosterone, Vardenafil

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tameside Hospital NHS Foundation Trust: lead

Study Sites (2)

Tameside General Hospital

Ashton-under-Lyne, Lancashire, OL6 9RW, United Kingdom

Location

Tameside Hospital NHS Foundatoin Trust

Ashton-under-Lyne, OL69RW, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypogonadism

Interventions

Testosterone; testosterone undecanoate; Vardenafil Dihydrochloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Edward Jude, MD, MRCP

  Tameside Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Physician

Study Record Dates

• First Submitted: March 9, 2010
• First Posted: March 10, 2010
• Study Start: October 11, 2013
• Primary Completion: September 14, 2014
• Study Completion: September 14, 2014
• Last Updated: April 4, 2019

Record last verified: 2019-04

Locations

GB (2)