Study of Testosterone vs Placebo in Testicular Cancer Survivors (Einstein)

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

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.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Testicular Cancer; Leydig Cell Failure in Adult
• Intervention / Treatment: Drug: Placebos; Drug: Testosterone

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).

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tostran 2%; 1 years treatment with transdermal Tostran 2%	Drug: Testosterone; Other Names: Tostran
Placebo Comparator: Placebo; 1 years treatment with placebo gel	Drug: Placebos

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

Collaborators and Investigators

• Sponsor: Mikkel Bandak

Publications and helpful links

General Publications

• Kreiberg M, Jørgensen 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.
• 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.
• Priskorn L, Kreiberg M, Bandak M, Lauritsen J, Daugaard G, Petersen JH, Aksglaede L, Juul A, Jørgensen 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: November 25, 2016
• First Submitted That Met QC Criteria: December 9, 2016
• First Posted (Estimate): December 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 5, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Endocrine System Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Genital Neoplasms, Male; Testicular Diseases; Insulin Resistance; Hyperinsulinism; Testicular Neoplasms; Metabolic Syndrome; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: 010815Testis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No