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

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

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes; Hypogonadism
• Intervention / Treatment: Drug: Testosterone

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Ashton under Lyne, United Kingdom, OL69RW
    • Tameside Hospital NHS Foundatoin Trust
  • Lancashire
    • Ashton-under-Lyne, Lancashire, United Kingdom, OL6 9RW
      • Tameside General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in endothelial dependent and endothelial-independent vasodilatation	Improvement in markers of endothelial function	30 and 54 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Markers of endothelial function	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	54 weeks

Collaborators and Investigators

• Sponsor: Tameside Hospital NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 11, 2013
• Primary Completion (ACTUAL): September 14, 2014
• Study Completion (ACTUAL): September 14, 2014

Study Registration Dates

• First Submitted: March 9, 2010
• First Submitted That Met QC Criteria: March 9, 2010
• First Posted (ESTIMATE): March 10, 2010

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Endothelial dysfunction; Type 2 diabetes; Hypogonadism; Testosterone
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypogonadism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Androgens; Anabolic Agents; Testosterone; Vardenafil Dihydrochloride; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: Testosterone version1