Study of Testosterone vs Placebo in Testicular Cancer Survivors (Einstein)
Primary Purpose
Metabolic Syndrome, Testicular Cancer, Leydig Cell Failure in Adult
Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Testosterone
Placebos
Sponsored by
About this trial
This is an interventional treatment trial for Metabolic Syndrome
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.
Sites / Locations
- Rigshospitalet
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tostran 2%
Placebo
Arm Description
1 years treatment with transdermal Tostran 2%
1 years treatment with placebo gel
Outcomes
Primary Outcome Measures
Changes in insulin sensitivity
Evaluation of changes in two hours plasma glucose investigated by Oral Glucose Tolerance Test (OGTT)
Secondary Outcome Measures
Changes in fasting plasma lipids between baseline and 52 weeks
Changes in BMD and fat percent between baseline 52 weeks
BMD and body composition evaluated by DXA-scan
Changes in systemic inflammation between baseline and 52 weeks
Analysis of tnf-alfa, interleukine 1-beta, interleukine 1, interleukine 6, interleukine 8
Changes in plasma-adipocytokines between baseline and 52 weeks
Changes in fasting plasma glucose between baseline and 52 weeks
Changes in Quality of life between baseline and 52 weeks.
EORTC-QLQ C30
Adverse events evaluated by the Common Terminology Criteria for Adverse Events Version 4.0
Changes in prevalence of metabolic syndrome between baseline and 52 weeks
According to NCEP-ATPIII criteria
Changes in haemoglobin A1c between baseline and 52 weeks
Changes in plasma insulin between baseline and 52 weeks
Changes in fatigue between baseline and 52 weeks
MFI-20 (Multidimensional Fatigue Inventory)
Changes in Anxiety and depression between baseline and 52 weeks
HADS (Hospital Anxiety and Depression Scale)
Changes in Symptoms of low levels of testosterone, erectile dysfunction between baseline and 52 weeks
IIEF-15 (International Index of Erectile Dysfunction)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02991209
Brief Title
Study of Testosterone vs Placebo in Testicular Cancer Survivors
Acronym
Einstein
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
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
November 2016 (undefined)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Mikkel Bandak
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome, Testicular Cancer, Leydig Cell Failure in Adult
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tostran 2%
Arm Type
Experimental
Arm Description
1 years treatment with transdermal Tostran 2%
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
1 years treatment with placebo gel
Intervention Type
Drug
Intervention Name(s)
Testosterone
Other Intervention Name(s)
Tostran
Intervention Type
Drug
Intervention Name(s)
Placebos
Primary Outcome Measure Information:
Title
Changes in insulin sensitivity
Description
Evaluation of changes in two hours plasma glucose investigated by Oral Glucose Tolerance Test (OGTT)
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Changes in fasting plasma lipids between baseline and 52 weeks
Time Frame
1 year
Title
Changes in BMD and fat percent between baseline 52 weeks
Description
BMD and body composition evaluated by DXA-scan
Time Frame
1 year
Title
Changes in systemic inflammation between baseline and 52 weeks
Description
Analysis of tnf-alfa, interleukine 1-beta, interleukine 1, interleukine 6, interleukine 8
Time Frame
1 year
Title
Changes in plasma-adipocytokines between baseline and 52 weeks
Time Frame
1 year
Title
Changes in fasting plasma glucose between baseline and 52 weeks
Time Frame
1 year
Title
Changes in Quality of life between baseline and 52 weeks.
Description
EORTC-QLQ C30
Time Frame
1 year
Title
Adverse events evaluated by the Common Terminology Criteria for Adverse Events Version 4.0
Time Frame
1 year
Title
Changes in prevalence of metabolic syndrome between baseline and 52 weeks
Description
According to NCEP-ATPIII criteria
Time Frame
1 year
Title
Changes in haemoglobin A1c between baseline and 52 weeks
Time Frame
1 year
Title
Changes in plasma insulin between baseline and 52 weeks
Time Frame
1 year
Title
Changes in fatigue between baseline and 52 weeks
Description
MFI-20 (Multidimensional Fatigue Inventory)
Time Frame
1 year
Title
Changes in Anxiety and depression between baseline and 52 weeks
Description
HADS (Hospital Anxiety and Depression Scale)
Time Frame
1 year
Title
Changes in Symptoms of low levels of testosterone, erectile dysfunction between baseline and 52 weeks
Description
IIEF-15 (International Index of Erectile Dysfunction)
Time Frame
1 year
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35701334
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.
Results Reference
derived
PubMed Identifier
35514022
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.
Results Reference
derived
PubMed Identifier
34223605
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.
Results Reference
derived
PubMed Identifier
28673265
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.
Results Reference
derived
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Study of Testosterone vs Placebo in Testicular Cancer Survivors
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