To assess the effects of testosterone replacement therapy on fat mass and other components of the metabolic syndrome.
ID
Source
Brief title
Condition
- Endocrine disorders of gonadal function
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is the change in fat mass as measured by Dual-Energy X-ray
Absorption (DEXA) scan after 20 weeks of Androgel compared to placebo.
Secondary outcome
Secondary endpoints are changes in fat mass between 20 and 40 weeks, and
changes in abdominal visceral fat, BMI, adipocytokines, metabolic syndrome
parameters, bone mass density, semen quality, sexual function, and quality of
life between Androgel and placebotreated
patients.
Background summary
Testicular cancer (TC) survivors have an increased risk of hypogonadism
(decreased testosterone and/or increased luteinizing hormone levels) and
cardiovascular disease (CVD). Metabolic syndrome develops early after
chemotherapy in 20-30% of longterm TC survivors and is associated with an
increased risk of atherosclerotic disease in the general population. TC
survivors who develop the metabolic syndrome have a higher body mass index
(BMI) pretreatment, a larger BMI increase during follow-up, and lower total
testosterone levels than patients without the metabolic syndrome. Testosterone
replacement therapy as a short-term intervention during a limited time period
may be an important
strategy to reduce body weight and fat mass, restore cardiometabolic balance,
and decrease the prevalence of the metabolic syndrome in TC survivors.
Study objective
To assess the effects of testosterone replacement therapy on fat mass and other
components of the metabolic syndrome.
Study design
Randomized double-blind placebo controlled intervention study, followed by an
open-label treatment phase. Results of this pilot study will be used to design
a multicenter randomized controlled study in a large group of TC survivors.
Intervention
Patients will be randomized to treatment with transdermal testosterone gel
(Androgel) or placebo gel once daily during 20 weeks, followed by 20 weeks of
active Androgel treatment in all participants. The treatment dose will be 50 mg
daily, adjusted to 25 mg in case of increased testosterone concentrations
(average of 2 measurements >25 nmol/L) or signs of overdosing. Patients will be
stratified according to testosterone level (8-12 nmol/L versus <8 nmol/L) and
BMI (25-30 kg/m2 versus 30-35 kg/m2).
Study burden and risks
The study will provide an answer to the question whether testosterone
replacement therapy as a short-term intervention has significant effects on
obesity and fat metabolism and may, thus, reduce the prevalence of the
metabolic syndrome in this population of young men with excellent long-term
cancer-related prognosis, but an increased CVD risk. At various time points
during the intervention, patients will be subjected to history taking and
physical examination. Furthermore, blood will be drawn to: measure hormone
levels, adipocytokines, lipids, glucose, insulin, bone and senescence markers;
to extract DNA for determination of gene polymorphisms; and to measure
hematocrit and PSA as safety parameters. Semen analysis and a full body DEXA
scan will be performed at 0, 20 and 40 weeks only. Patients will be asked to
fill out questionnaires
regarding quality of life, sexual health, and androgen deficiency symptoms at
various time points during the intervention.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
We will include patients with metastatic testicular cancer after chemotherapy,
at least 12 months after completion of last treatment and without evidence of
disease. Combination chemotherapy should have contained a platinum compound,
either cisplatin or carboplatin. In TC survivors, testosterone levels are
routinely measured in blood during follow-up once every two years. Patients are
eligible for screening if they are between 18 and 55 years of age, and have a
documented low or low-normal total testosterone level <=14 nmol/L, as measured
during any of the follow-up visits, irrespective of signs and symptoms of
androgen deficiency. Eligible for actual study participation and randomization
between Androgel and placebo will be: survivors of TC not using testosterone
supplements, having biochemical evidence of hypogonadism (defined as a serum
total testosterone
concentration <= 12 nmol/L (345 ng/dL) measured after an overnight fast between
8:00 and 10:00
AM), and being overweight (as defined by a BMI >= 25 and <35 kg/m2). Patients
should be able
to understand and abide to the study protocol and sign written informed
consent.
Exclusion criteria
We will exclude: patients planning to father children within the next 12
months; patients already treated for hypogonadism, patients taking
corticosteroids or hormone replacement other than testosterone with
dose-adjusments within the last 3 months prior to randomization; patients
taking medication with any antiandrogenic effects (e.g. spironolactone);
patients with signs or history of hormone-dependent cancer (prostate or breast
cancer); patients with severe lower
urinary tract symptoms (as defined by International Prostate Symptom Score
>19); patients
with a history of coronary artery disease (angina pectoris, myocardial
infarction) or heart
failure; patients with hematocrit >50%; patients with untreated severe
obstructive sleep apnea;
patients with uncontrolled hypertension; patients with a BMI > 35 kg/m2;
patients with a history of
epilepsy; patients with debilitating psychiatric illness or inability to
understand the study protocol,
according to the opinion of the investigator.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004430-96-NL |
| ClinicalTrials.gov | NCT03339635 |
| CCMO | NL57224.042.17 |