Study of Testosterone vs Placebo in Testicular Cancer Survivors

Study Overview
=================
Brief Summary
-----------------
The overall purpose of the study is to evaluate the effect of 12 months testosterone replacement therapy in testicular cancer survivors with mild Leydig Cell Insufficiency in order to reduce the risk of cardiovascular disease. The primary study objective is to evaluate changes in insulin sensitivity. The secondary study objective is to evaluate changes in the prevalence of metabolic syndrome, body composition, systemic inflammation and symptoms of testosterone deficiency.

Detailed Description
-----------------
This is a single-center, randomized, double-blind, placebo-controlled intervention study, designed to evaluate the effect of testosterone replacement therapy in testicular cancer survivors with mild Leydig Cell Insufficiency. 70 subjects will be randomized to receive either testosterone replacement therapy or placebo. The subjects will be invited for an information meeting where informed consent is signed. If a subject is suitable for participation in the trial, subject will be randomized to testosterone replacement therapy or placebo and baseline investigations will be performed. Afterwards, a 52-weeks treatment period begins in which subjects receive a daily dose of testosterone or placebo. Dose adjustment will be made three times during the first 8 weeks of the study. Evaluation of primary and secondary endpoints will be performed after 26 weeks, at the end of treatment (52 weeks) and three months after completion of treatment (week 64).

Official Title
-----------------
A Randomized Double-blind Study of Testosterone Replacement Therapy or Placebo in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency (Einstein-intervention)

Conditions
-----------------
Metabolic Syndrome, Testicular Cancer, Leydig Cell Failure in Adult

Intervention / Treatment
-----------------
* Drug: Testosterone
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent. Previous treatment for testicular cancer. No signs of relapse 1 year after last treatment (orchiectomy, radiotherapy, chemotherapy). Free testosterone < the age-adjusted median and > -2 standard deviations (SD) from the age-adjusted median and LH > 2 SD from the age-adjusted median. Exclusion Criteria: Treatment with testosterone within the last 6 months. Contraindications to testosterone treatment (prostate cancer, prostate specific antigen (PSA)> 4 ng/mL), malignancy suspect prostate by digital rectal examination, Alanine aminotransferase (ALT)> 1.5 upper reference level, Erythrocyte Volume Fraction (EVF) > 50%. Breast cancer. Symptomatic obstructive sleep apnoea syndrome Heart failure > NYHA II. Uncontrolled hypertension: (Systolic blood pressure > 160 mm Hg despite antihypertensive treatment, measured at two separate occasions) Inability to understand information about the trial Participation in any other clinical trial Allergy for the active substance or additives in Tostran or placebo. Known diabetes mellitus, or diabetes mellitus detected at screening or baseline tests.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tostran 2%<br>1 years treatment with transdermal Tostran 2% | Drug: Testosterone<br> <br> * Other names: Tostran;|
| Placebo Comparator: Placebo<br>1 years treatment with placebo gel | Drug: Placebos<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in insulin sensitivity | Evaluation of changes in two hours plasma glucose investigated by Oral Glucose Tolerance Test (OGTT) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in fasting plasma lipids between baseline and 52 weeks |  | 1 year | 
| Changes in BMD and fat percent between baseline 52 weeks | BMD and body composition evaluated by DXA-scan | 1 year | 
| Changes in systemic inflammation between baseline and 52 weeks | Analysis of tnf-alfa, interleukine 1-beta, interleukine 1, interleukine 6, interleukine 8 | 1 year | 
| Changes in plasma-adipocytokines between baseline and 52 weeks |  | 1 year | 
| Changes in fasting plasma glucose between baseline and 52 weeks |  | 1 year | 
| Changes in Quality of life between baseline and 52 weeks. | EORTC-QLQ C30 | 1 year | 
| Adverse events evaluated by the Common Terminology Criteria for Adverse Events Version 4.0 |  | 1 year | 
| Changes in prevalence of metabolic syndrome between baseline and 52 weeks | According to NCEP-ATPIII criteria | 1 year | 
| Changes in haemoglobin A1c between baseline and 52 weeks |  | 1 year | 
| Changes in plasma insulin between baseline and 52 weeks |  | 1 year | 
| Changes in fatigue between baseline and 52 weeks | MFI-20 (Multidimensional Fatigue Inventory) | 1 year | 
| Changes in Anxiety and depression between baseline and 52 weeks | HADS (Hospital Anxiety and Depression Scale) | 1 year | 
| Changes in Symptoms of low levels of testosterone, erectile dysfunction between baseline and 52 weeks | IIEF-15 (International Index of Erectile Dysfunction) | 1 year |