Clinical trial NCT02991209: Study of Testosterone vs Placebo in Testicular Cancer Survivors
Official title: A Randomized Double-blind Study of Testosterone Replacement Therapy or Placebo in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency (Einstein-intervention)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Metabolic Syndrome
Testicular Cancer
Leydig Cell Failure in Adult
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2016-12-13
Enrollment: 69
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Changes in insulin sensitivity
timeFrame: 1 year
Secondary outcomes:
measure: Changes in fasting plasma lipids between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in BMD and fat percent between baseline 52 weeks
timeFrame: 1 year
measure: Changes in systemic inflammation between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in plasma-adipocytokines between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in fasting plasma glucose between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in Quality of life between baseline and 52 weeks.
timeFrame: 1 year
measure: Adverse events evaluated by the Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: 1 year
measure: Changes in prevalence of metabolic syndrome between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in haemoglobin A1c between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in plasma insulin between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in fatigue between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in Anxiety and depression between baseline and 52 weeks
timeFrame: 1 year
measure: Changes in Symptoms of low levels of testosterone, erectile dysfunction between baseline and 52 weeks
timeFrame: 1 year
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
References:
citation: Kreiberg M, Jorgensen N, Juul A, Lauritsen J, Oturai P, Helge JW, Christensen JF, Aksglaede L, Schauer T, Wagner T, Rosenvilde J, Grunwald E, Dehlendorff C, Daugaard G, Bandak M. A randomized double-blind single center study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention). Clin Genitourin Cancer. 2022 Oct;20(5):404-414. doi: 10.1016/j.clgc.2022.04.017. Epub 2022 May 2.
citation: Hojer EG, Kreiberg M, Dehlendorff C, Jorgensen N, Juul A, Lauritsen J, Wagner T, Rosenvilde J, Daugaard G, Bandak M. Effect of Testosterone Replacement Therapy on Quality of Life and Sexual Function in Testicular Cancer Survivors With Mild Leydig Cell Insufficiency: Results From a Randomized Double-blind Trial. Clin Genitourin Cancer. 2022 Aug;20(4):334-343. doi: 10.1016/j.clgc.2022.03.012. Epub 2022 Apr 1.
citation: Priskorn L, Kreiberg M, Bandak M, Lauritsen J, Daugaard G, Petersen JH, Aksglaede L, Juul A, Jorgensen N. Testicular cancer survivors have shorter anogenital distance that is not increased by 1 year of testosterone replacement therapy. Hum Reprod. 2021 Aug 18;36(9):2443-2451. doi: 10.1093/humrep/deab162.
citation: Bandak M, Jorgensen N, Juul A, Lauritsen J, Kreiberg M, Oturai PS, Helge JW, Daugaard G. A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention). BMC Cancer. 2017 Jul 3;17(1):461. doi: 10.1186/s12885-017-3456-5.