Clinical trial NCT04545450: Effects of Testosterone Plus Dutasteride or Placebo on Muscle Strength, Body Composition and Metabolism in Transmen
Official title: A Randomized Double-blind Placebo-controlled Pilot Trial on the Effects of Testosterone Undecanoate Plus Dutasteride or Placebo on Muscle Strength, Body Composition and Metabolic Profile in Transmen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Transgenderism
Hypogonadism
Keywords: Muscle strenght
Testosterone
Dutasteride
dihydrotestosterone
5a-reductase inhibitor
Lead sponsor: Unita Complessa di Ostetricia e Ginecologia
Sponsor class: OTHER
First posted: 2020-09-11
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To compare the effects on body composition and muscle strengthof 54-weeks treatment with of testosterone undecanoate combined with placebo or with the 5a-reductase inhibitor dutasteride

Detailed description: Transmen who have undergone gender-affirming surgery require long-lasting treatments with androgens to maintain male phenotypic characteristics and to preserve their health. In this population the effects on muscle and the relative role of testosterone and its metabolite dihydrotestosterone (DHT) on the skeletal muscle are still largely unknown.

In this pilot study, we evaluated the effects of testosterone and DHT on muscle strength, body composition, metabolism. Also cutaneous androgenic effects such as acne and androgenetic alopecia were evaluated.

DESIGN

For this purpose, in this randomized, double-blind placebo-controlled pilot trial we treated variectomized transmen for 54 weeks with:

* Testosterone Undecanoate (TU) 1000 mg i.m. at weeks zero, six, 18, 30, 42 + a daily oral placebo pill (TU+PL)
* TU 1000 mg i.m. at weeks zero, six, 18, 30, 42 + dutasteride 5 mg/day (TU+DUT).

Prospective, phase III, randomized study design was used.

Subjects were seen every 12 weeks for safety monitoring that included evaluation of hematocrit, transaminases, alkaline phosphatases and bilirubin, creatinine, urea and serum electrolyte as potassium and sodium.

Baseline and week-54 evaluations included the following measurements:

blood drawings for measurements of: hormonal profile (serum testosterone, estradiol, luteinizing hormone and follicle-stimulating hormone, prolactin, sex hormone binding globulin, and thyroid stimulating hormone), haematocrit (Ht) and haemoglobin (Hb), glucidic and lipidic profile (fasting glucose, fasting insulin, total cholesterol, high- and low-density lipoproteins, and triglycerides), hepatic function (aspartate and alanine aminotransferases) and bone related markers (osteocalcin, parathyroid hormone, bone alkaline phosphatase and 25-hydroxyvitamin, 24h urinary excretion of calcium, potassium, magnesium and creatinine).

anthropometry: weight, measures DEXA for bone mass determination and body composition Isokinetic knee extension and flexion peak torque (PT-IKE and PT-IKF) Handgrip strength evalutation of the psychological profile with the brief Profile of Mood State (POMS) sexual life satisfaction evalutation with a Visual Analogue General Satisfaction Scale (VAS) physical examination: inspection of external genitalia (clitorides) and a visit to detect appearance of acne and gynecomastia

During the treatment phase all injections will be administered by the investigator or co-investigators for the entire study. Fasting (10 hours) blood samples will be taken (immediately before giving the injections) every time subjects come for injections (week 0, 6, 18, 30 and 42) and at the end of the treatment phase.

In the sexual and behavior questionnaire the subjects will judge their sexual activity and behavior in the period between visits. The subjects have the possibility to making additional comments about important events and disturbances.

Eligibility criteria: Inclusion Criteria:

* Healthy transmen
* Previous bilateral gonadectomy during sex reassigning surgery
* Body Mass Index (BMI) between 20 and 29 kg/m²; (body weight in kilograms divided by body height in meters squared)
* Clinical examination without pathological findings relevant to the study
* No concomitant use of drugs known to affect the hypothalamic-pituitary-ovarian axis
* Written Consent Form
* High probability of a good compliance and termination of the study

Exclusion Criteria:

* Participation in another clinical trial within the 30 days preceding the first administration
* Simultaneous participation in another clinical trial
* Subjects institutionalized or imprisoned by order of the court
* Subject who compete in sports
* Subjects reporting desire to perform regular physical exercises for the duration of the study
* Serious organic or psychic disease suspected from history and/or clinical examination
* Diseases (especially tumors) that might represent an actual contraindication for testosterone
* Past or present history of thrombotic or embolic diseases
* Arterial hypertension
* Diabetes mellitus
* Acute or chronic hepatic diseases
* Manifest renal diseases with renal dysfunction
* Severe internal diseases
* Biochemical and/or hematological laboratory values beyond normal ranges unless the Investigator confirms that the deviations are of no clinical relevance
* Any indication of chronic use of drugs, alcohol, opiates or recreational drugs
* Use of any drug known to affect biotransformation of testosterone and/or progestin, e.g. chlorcycline, phenobarbital, phenylbutazone, aminophenazone within the 30 days preceding the first administration of the test medication and during the study
* Use of oral anticoagulatory drugs within the 30 days preceding the first administration of the test medication and during the study
* Any oral or transdermal hormone medication within the 12 weeks preceding the first administration and during the study
* Probability of poor compliance and termination of the study

Primary outcomes:
measure: Change in isokinetic knee extension and flexion peak torque (PT-IKE and PT-IKF)
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in handgrip strength
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in body composition
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in bone mineral density
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in anthropometric assessment: BMI
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in anthropometric assessment: waist-to-hip ratio
timeFrame: At baseline and after 54 weeks of treatment
Secondary outcomes:
measure: Change in psychological profile with the brief Profile of Mood State (POMS)
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in the satisfaction with their sexual life
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in in the bone metabolism: osteocalcin
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in in the bone metabolism: parathyroid hormone
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in in the bone metabolism: bone alkaline phosphatase
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in in the bone metabolism: urinary excretion of electrolites
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in in the insulin resistance
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in the lipid profile
timeFrame: At baseline and after 54 weeks of treatment
measure: Change in the lipid profile
timeFrame: At baseline and after 54 weeks of treatment
Other outcomes:
Locations:
Study officials:
References: