Effects of Transdermal Testosterone and/or Monthly Vitamin D on Fall Risk in Pre--frail Hypogonadal Seniors. Double Blind, 2x2 Factorial, Randomized Placebo--Controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 91
- 试验地点
- 1
- 主要终点
- Number of fallers
研究概览
简要总结
The overall purpose of this study is to test the individual and combined effect of transdermal testosterone and/or Vitamin D in reducing fall risk and improve function in pre-frail hypogonadal senior men.
详细描述
Background:
One of the challenges of demographic change is the enormous personal and economic burden of falls and their consequences in the senior population. Thirty percent of adults 65 years or older and 40 - 50% of those age 80 years or older fall once per year. Serious injuries occur in 10 - 15% of falls, resulting in fractures in 5% and a hip fracture in 1-2% of cases. As an independent determinant of functional decline, falls lead to 40% of all nursing home admissions.
Several studies have estimated the prevalence of low testosterone levels (hypogonadism) in older men to be about 20% at age 60. This proportion increased in the Baltimore Longitudinal Study of Aging with each decade (30% at age 70 and 50% at age 80). Low testosterone levels are associated with decreased strength, impaired physical performance, and an increased risk of falls, and, thus, low testosterone may contribute to the frailty syndrome in older men. Current studies have focused on healthy, community dwelling men with a high level of function. Our trial aims to enrol pre-frail senior men at risk of losing their autonomy. Further, in this population and also relevant for muscle health and falling is the high prevalence of vitamin D deficiency.
Dose Rationale:
The investigators chose 75 mg testosterone/day as the minimally sufficient dose to shift over 90% of participants to total testosterone levels of at least 16.86 nmol/l (lower end of the third quartile in the pilot trial where fall reduction was significant -- Bischoff-Ferrari et al.; Osteoporosis International 2008). Additionally, this dose has been chosen for its cardiovascular safety as summarized in a 2013 review.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men with documented total testosterone levels < 11.30 nmol/l
- •Able to come to the study centre (Community-dwelling or institutionalized)
- •Age 65+ years
- •At a higher risk for falling
- •Body mass index > 18.0 and < 35.0 kg/m2
- •Understands German in reading and writing plus able to read, understand, and complete questionnaires and tests.
- •Willingness to limit additional vitamin D3 intake to a maximum of 800 IU per day
- •Willingness to limit calcium supplement intake to 500 mg/day
- •Willingness to stop active vitamin D metabolites
- •Willingness to forgo any additional use/application of testosterone products for the duration of the trial.
- •Participant understands the study procedures, alternative treatments available and risks involved with the study and voluntarily agrees to participate by giving a written informed consent.
- •Participant meets the routine clinical laboratory safety screening tests performed at screening visit.
- •Participant is able and willing to perform all study tests, attend all required office visits, and provide blood and urine samples.
- •Participant is able to apply the testosterone/placebo gel and is able to drink the vitamin D/placebo solution.
- •Participant is mentally competent (judicious) defined by having score > 24 on the Folstein's mini mental state examination (MMSE) at the screening visit.
排除标准
- •Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product
- •Treatment with vitamin K-antagonists, insulin, adrenocorticotropic hormone (ACTH), corticosteroid (>5mg/d)
- •Elevated (≥ 4.0 ng/ml) prostate-specific antigen levels (at screening) and/or palpable signs of prostate cancer
- •Palpable signs of breast-cancer
- •Haemoglobin ≤ 100 g/l
- •Haematocrit ≥ 0.50 L/L
- •Liver function values (alanine aminotransferase, aspartate aminotransferase, Gamma-glutamyl transferase, alkaline phosphatase) more than 3 times the upper limit of normal.
- •Consumption of >800 IU vitamin D on any day in the 6 months prior to enrolment. Provision: a person can be enrolled as soon as the mean intake in the last 6 months and since the last dose is ≤ 800 IU.
- •Elevated serum calcium ≥ 2.60 mmol/l (adjusted for albumin )
- •Estimated (Cockcroft and Gault formula ) creatinine clearance ≤ 30 ml/min
- •Severe visual or hearing impairment
- •History of cancer < 5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer
- •Myocardial infarction in the last 3 months, unstable angina pectoris and/or exertional dyspnoea >=NYHA III
- •Treatment worthy but untreated sleep apnoea or chronic (obstructive) pulmonary disease, epilepsy
- •Significant end-stage disease, i.e. genitourinary, cardiovascular, hepatic, renal, endocrine, hematologic, psychiatric, or pulmonary disease, which, in the opinion of the investigator, may pose a high risk to the patient or impair the patient's ability to complete the trial or confound the results
- •Uncontrolled hypertension (blood pressure mm Hg ≥ 180 systolic or ≥ 110 diastolic)
- •Alcohol abuse or alcoholic disease
- •Participation in another interventional research trial within the last 6 months prior to screening
- •Severe gait impairment, e.g. due to Parkinson's disease or hemiplegia
- •Previous enrolment into the current study
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
研究组 & 干预措施
Testosterone + Vitamin D
Testosterone, transdermal gel, 75 mg, once per day, for 12 months AND Colecalciferol, oral drink solution, 24000 IU, once per month, for 12 months
干预措施: Testosterone (Drug)
Testosterone + Vitamin D
Testosterone, transdermal gel, 75 mg, once per day, for 12 months AND Colecalciferol, oral drink solution, 24000 IU, once per month, for 12 months
干预措施: Colecalciferol (Drug)
Testosterone + Placebo
Testosterone, transdermal gel, 75 mg, once per day, for 12 months AND Placebo: Colecalciferol, oral drink solution, 0 IU, once per month, for 12 months
干预措施: Testosterone (Drug)
Testosterone + Placebo
Testosterone, transdermal gel, 75 mg, once per day, for 12 months AND Placebo: Colecalciferol, oral drink solution, 0 IU, once per month, for 12 months
干预措施: Placebo drink solution (Drug)
Placebo + Vitamin D
Placebo: Testosterone, transdermal gel, 0 mg, once per day, for 12 months AND Colecalciferol, oral drink solution, 24000 IU, once per month, for 12 months
干预措施: Colecalciferol (Drug)
Placebo + Vitamin D
Placebo: Testosterone, transdermal gel, 0 mg, once per day, for 12 months AND Colecalciferol, oral drink solution, 24000 IU, once per month, for 12 months
干预措施: Placebo transdermal gel (Drug)
Control
Placebo: Testosterone, transdermal gel, 0 mg, once per day, for 12 months AND Placebo: Colecalciferol, oral drink solution, 0 IU, once per month, for 12 months
干预措施: Placebo drink solution (Drug)
Control
Placebo: Testosterone, transdermal gel, 0 mg, once per day, for 12 months AND Placebo: Colecalciferol, oral drink solution, 0 IU, once per month, for 12 months
干预措施: Placebo transdermal gel (Drug)
结局指标
主要结局
Number of fallers
时间窗: 12 months
The participant will fill in a falls diary.
Rate of falls
时间窗: 12 months
The participant will fill in a falls diary.
次要结局
- Quality of life(12 months)
- Lower extremity function(12 months)
- Appendicular lean skeletal muscle mass (aLSM)(12 months)
- Reaction time(12 months)
- Gait Speed(12 months)