01.12.2017 | Study protocol | Ausgabe 1/2017 Open Access

A randomized double-blind study of testosterone replacement therapy or placebo in testicular cancer survivors with mild Leydig cell insufficiency (Einstein-intervention)
- Zeitschrift:
- BMC Cancer > Ausgabe 1/2017
Background
Methods/design
Study subjects
Inclusion criteria
- Age > 18 years and <65 years
- Previous treatment for testicular cancer
- No signs of relapse 1 year after the last treatment (orchiectomy, radiotherapy, chemotherapy)
- Serum free testosterone < the age-adjusted mean value and >2 standard deviations (SD) below the age-adjusted mean value
- Serum luteinizing hormone (LH) > 2 SD above the age-adjusted mean value
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Exclusion criteria
- Testosterone treatment 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 (ALT) > 1.5 upper limit of normal, erythrocyte volume fraction (EVF) > 50%, breast cancer
- Symptomatic obstructive sleep apnoea syndrome
- Heart failure > New York Heart Association class II
- Uncontrolled hypertension: (Systolic blood pressure > 160 mmHg 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 at baseline
- Paternity wish at the time of inclusion
a
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Recruitment and informed consent
Randomization and procedures for breakage of randomization code
Blinding
Intervention
Dose adjustment
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Dose modifications
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Follow-up
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Starting dose: 10 mg daily
(one depression of the piston)
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Week 2: 20 mg daily
(two depressions of the piston)
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Week 4: 30 mg daily
(three depressions of the piston)
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Week 8: 40 mg daily
(four depressions of the piston)
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52 weeks: End of treatment
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Safety issues
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Increase in free testosterone to >3 SD above the age-adjusted mean
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Dose adjustment to previous treatment step
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Measurement of free testosterone and LH after 14 days and dose adjustment accordingly
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Decrease in LH to < −2 SD below the age-adjusted mean
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Dose adjustment to previous treatment step
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Measurement of free testosterone and LH after 14 days and dose adjustment accordingly
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Increase in EVF to >52%
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Dose adjustment to previous treatment step
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Measurement of EVF after 14 days and dose adjustment accordingly
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Plasma PSA > 4 ng/mL at any visit. A PSA increase of >1 ng/mL at visit 7 or visit 8, using plasma PSA at visit 6 as baseline
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Referral for urological consultation
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According to urological consultation: Stop treatment if increased risk of prostate cancer. Continue treatment at the same treatment step if there is no increased risk of prostate cancer
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An increase in systolic blood pressure > 20 mmHg confirmed at two separate measurements despite antihypertensive therapy, if not due to free testosterone being >3 SD from the age-adjusted mean
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Stop treatment
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Measurement of blood pressure after 14 days. If still elevated referral to general practitioner
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ALT increase >1.5 upper reference level
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Stop treatment
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Measurement of ALT after 14 days. If still elevated referral for hepatological consultation
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Any other exclusion criteria becoming apparent during treatment
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Stop treatment
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Dose modifications
Planned inclusion
Measurements
Data assessment
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Screening
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Baseline
Week 0
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Dose adjustment 1
Week 2
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Dose adjustment 2
Week 4
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Dose adjustment 3
Week 8
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On treatment
Week 26
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Last dose
Week 52
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Follow-up
Week 64
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hCG-stimulation test
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Blood pressure
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x
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x
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x
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x
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x
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Blood samples
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x
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x
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x
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x
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x
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x
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Waist circumference
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x
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x
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x
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x
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DXA scan
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x
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x
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x
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x
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Oral glucose tolerance test
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x
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x
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x
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x
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Questionnaires
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x
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x
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Anogenital distance
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x
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x
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Randomization
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x
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On treatment
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x
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x
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x
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x
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x
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x
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Dose adjustment
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x
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x
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x
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Evaluation of side effects
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x
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x
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x
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x
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x
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x
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x
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Systemic effects
- Glucose metabolism (fasting glucose, 2 h glucose, insulin, hemoglobin a1c, HOMA-index)
- Cholesterol (high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, total cholesterol)
- Inflammatory markers (interleukin 1-β, interleukin-6, interleukin-8, tumour necrotic factor-alpha)
- Adipocytokines (adiponectin, leptin)
- Reproductive hormones (total testosterone, free testosterone, luteinizing hormone)
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Body composition and bone mineral density
- Whole body bone mineral density, whole body t-score, t-score of the lumbar spine and proximal femoral bone
- Lean body mass
- Whole body fat percent (Z-score)
- Visceral adiposity, android fat distribution, gynoid fat distribution
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Anthropomorphic measures
- Waist circumference
- Hip circumference
- Body mass index
- Anogenital distance
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Patient reported outcomes
- Health related quality of Life (EORTC QLQ-C30)
- Anxiety and Depression: (Hospital Depression and Anxiety Scale)
- Fatigue: (Multiple Fatigue Inventory-20)
- Symptoms of testosterone deficiency and erectile dysfunction: (International Index of Erectile Function-15)
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