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

Primary Purpose

Type 2 Diabetes, Hypogonadism

Status
Terminated
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Testosterone
Sponsored by
Tameside Hospital NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes focused on measuring Type 2 diabetes, Hypogonadism, Testosterone, Endothelial dysfunction

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Tameside General Hospital
  • Tameside Hospital NHS Foundatoin Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Testosterone, Vardenafil

Arm Description

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

Outcomes

Primary Outcome Measures

Improvement in endothelial dependent and endothelial-independent vasodilatation
Improvement in markers of endothelial function

Secondary Outcome Measures

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

Full Information

First Posted
March 9, 2010
Last Updated
April 2, 2019
Sponsor
Tameside Hospital NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT01084369
Brief Title
Effect of Testosterone on Endothelial Function and Microcirculation in Type 2 Diabetic Patients With Hypogonadism
Official Title
Phase IV: Effect of Testosterone on Endothelial Function and Microcirculation in Type 2 Diabetic Patients With Hypogonadism
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
Withdrawal of sponsorship
Study Start Date
October 11, 2013 (Actual)
Primary Completion Date
September 14, 2014 (Actual)
Study Completion Date
September 14, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tameside Hospital NHS Foundation Trust

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes, Hypogonadism
Keywords
Type 2 diabetes, Hypogonadism, Testosterone, Endothelial dysfunction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Testosterone, Vardenafil
Arm Type
Experimental
Arm Description
All patients will receive Testosterone (n=40) of these (10 patients) will also receive Vardenafil
Intervention Type
Drug
Intervention Name(s)
Testosterone
Other Intervention Name(s)
Testosterone (NEBIDO), Vardenafil (Levitra)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Improvement in endothelial dependent and endothelial-independent vasodilatation
Description
Improvement in markers of endothelial function
Time Frame
30 and 54 weeks
Secondary Outcome Measure Information:
Title
Markers of endothelial function
Description
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
Time Frame
54 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Jude, MD, MRCP
Organizational Affiliation
Tameside Hospital NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tameside General Hospital
City
Ashton-under-Lyne
State/Province
Lancashire
ZIP/Postal Code
OL6 9RW
Country
United Kingdom
Facility Name
Tameside Hospital NHS Foundatoin Trust
City
Ashton under Lyne
ZIP/Postal Code
OL69RW
Country
United Kingdom

12. IPD Sharing Statement

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

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