Short-term Testosterone Replacement in Testicular Cancer Survivors to Treat Overweight and Improve Cardiometabolic Risk: A Pilot Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- percent change in fat mass as measured using using full body dual X-ray absorptiometry
研究概览
简要总结
To assess the effects of testosterone replacement therapy on fat mass and other components of the metabolic syndrome. A 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
详细描述
Rationale: 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 long-term 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.
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
Study population: 40 TC patients, aged 18-55 years, at least 12 months after completion of curative treatment with unilateral orchidectomy and platinum-based chemotherapy, and having a fasting total testosterone level ≤12 nmol/l and a BMI ≥25 kg/m2.
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •patients with metastatic testicular cancer after unilateral orchidectomy and 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
- •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.
排除标准
- •patients with a history of extragonadal testicular cancer
- •patients planning to father children within the next 12 months
- •patients taking corticosteroids or hormone replacement other than testosterone within 3 months of 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
研究组 & 干预措施
Testosterone gel
Patients will be randomized to treatment with transdermal testosterone gel (Androgel) once daily during 20 weeks, followed by 20 weeks of active Androgel treatment in all participants.
干预措施: Androgel (Testosterone gel) (Drug)
Placebo gel
Patients will be randomized to treatment with placebo gel once daily during 20 weeks, followed by 20 weeks of active Androgel treatment in all participants.
干预措施: Androgel (Testosterone gel) (Drug)
Placebo gel
Patients will be randomized to treatment with placebo gel once daily during 20 weeks, followed by 20 weeks of active Androgel treatment in all participants.
干预措施: Placebo gel (Drug)
结局指标
主要结局
percent change in fat mass as measured using using full body dual X-ray absorptiometry
时间窗: 20 weeks of treatment
To assess the effects of 20 weeks of treatment with testosterone gel on fat mass as measured using full body dual X-ray absorptiometry (DEXA scan).
次要结局
- Effect of treatment with testosterone gel(20 and 40 weeks of treatment)