Effect of PROGRESSive Training and Teststerone in Older Frail Men

Study Overview
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Brief Summary
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In this scientific clinical investigation we will test whether testosterone and progressive resistance training can improve muscle strength and reduce the risk of falls in older men. In addition, we will examine whether this treatment improves quality of life, functional capacity, including sexual function and counteracts depression. Such a project have not been performed earlier.

Detailed Description
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Project background: In Denmark more than 1,000 people each year die of a fall, which is more than five times as many dying in traffic accidents. Fall accidents are also the leading cause of traumatic brain injury and is a relatively unnoticed problem, although this type of accidents causes more hospital bed days than all other accidents combined. Annually, almost half of the 375,000 elderly Danes over 75 years of age and relatively three times as many of the approximately 40,000 elderly people in nursing homes fall every year, causing over 40,000 hospital contacts annually. Ten percent of all elderly people hospitalized each year because of a fall, mostly with fractures, for which the risk increases fivefold after a fall. In Denmark there are now now around 1 million people over 65 years of age. Over the next 25 years we will experience a 50% growth to 1.5 million people over 65 years of age. Injury, disability and death caused by falls is therefore a widespread and growing human and societal problem. Many will never recover completely and will therefore need help to cope with everyday life. After the first fall risk increase for repeated falls. Especially for older people living in their own homes permanent or temporary disabilities results in a severe deterioration of the quality of life. Treatment of falls is also a significant financial burden on health and social care. The main reason for the decline is muscle weakness. Muscle weakness leads to greatly increased risk of falling, decreased quality of life and functional capacity. Musclemass and -power decrease about 40 percent from age 20 to 80 years old. Recent studies have shown that even 90-year-old persons can double their muscle strength by intensive training just three times per week. The level of the male sex hormone testosterone decreases with age and leads to impaired muscle mass. Twenty percent of men over 60 and 50 percent over 80 years, a low level of testosterone in total equivalent to more than 100,000 Danes. From the human and socio-economic perspective, it is important to find treatments that can enhance function in the elderly.

Official Title
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Effect of PROGRESSive Resistance Training, Protein Supplements and Testosterone in Older Frail Men With Testosterone Deficiency (PROGRESS Trial)

Conditions
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Muscle Weakness

Intervention / Treatment
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* Drug: testosterone
* Other: Progressive muscle training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Living in their own home or in sheltered accommodation. Independent gait possible. with tool. Capable of stand-up and sit in a chair at least 8 times in 30 sec. There must be at least 3 symptoms or objective findings of low testosterone . Serum testosterone <10nmol /L as the average of two independent measurements - Exclusion Criteria: Known or previous prostate cancer. Abnormally elevated serum PSA (PSA = prostate specific antigen) corresponding to PSA> 5 ng / ml or PSA> 0.15 ng / ml / cc (relative to the prostatic volume in cubic centimeters (cc)). Hæmatomacrose. Heart disease in the form of: peri-, myo-, or endocarditis, angina, severe heart failure (NYHA class III and IV), severe hypertension (systolic blood pressure> 180 or diastolic BT> 105 mmHg after antihypertensive therapy). Dyspnoea at rest. Liver (AST> 2 x ULN) or renal impairment (serum creatinine> 200 micromoles / L). Severe and insufficiently treated epilepsy or migraine. Insulin treatment. Previous or current bifosfonat-, fluoride, HRT, SERM-, strontium, teraparatid- or more than 3 weeks of prednisolone. Joint disease with acute inflammation. Active cancer disease in chemo- or radiotherapy. Bone metabolic disease apart from age-related osteoporosis. Autoimmune diseases, chronic systemic diseases (cirrhosis, AIDS, chronic renal failure). Primary testosterone deficiency in the form of testicular dysgenesis, Klinefelter syndrome (47, XXY), 46, XX males, LH-resistance, the Y chromosome deletions, other sex chromosome abnormalities ,. Significant abuse, mental illness, dementia, physical disability with inability to implement intervention or tests or to give informed consent. Contraindications to testosterone undecanoate is included in the exclusion criteria, such as. presence of liver tumors, breast and prostate cancer, as subjects will be examined before the trial starts.

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Controls<br>A control group, which is 20 weeks with placebo injections without training. | |
| Experimental: Testosterone<br>A testosterone group given 20 weeks on testosterone injections without training | Drug: testosterone<br>* Testosterone supplemented in 5 months<br>|
| Experimental: Training<br>A Training Group, which is 20 weeks with placebo injections and 16 weeks of progressive resistance training supplemented with vitamin D and protein supplements | Other: Progressive muscle training<br>* Progressive muscle training during 4 months<br>* Other names: Training;|
| Experimental: Testosterone and training<br>A combination group that is 20 weeks with testosterone injections and 16 weeks of progressive resistance training supplemented with vitamin D and protein supplements | Drug: testosterone<br>* Testosterone supplemented in 5 months<br>Other: Progressive muscle training<br>* Progressive muscle training during 4 months<br>* Other names: Training;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stand-up-and Sit-test | It is a measure of overall strength in the lower extremities. Result of the test is defined as the number of times the participant can stand up and sit from a chair in 30 seconds. There is a good correlation (r = 0.78) with a leg press and an acceptable test-retest reliability (ICC = 0.86). | up to 5 months (at study completion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of falls via questionaire | included in the monitoring of adverse events. | At baseline, 1 month, 5 months (at study completion) | 
| Balance ability, | Tandem Test containing three starting positions: 1) Standing with feet together, standing in the semi-tandem position and standing in the tandem stand. coupled with decrease risk of fall. | At baseline, 1 month, 5 months (at study completion) | 
| Avlund mobility scale | Questions about experiencing fatigue and support needs of ordinary everyday activities. Avlund mobility scale is correlated with the isometric muscle strength, simple function tests , increased risk of hospitalization and mortality | At baseline, 1 month, 5 months (at study completion) | 
| Leg extensor Power Rig test | An instrument for measuring muscle strength in the lower extremities. | At baseline, 1 month, 5 months (at study completion) | 
| Isometric muscle strength | Measurement of isometric muscle strength m. quadriceps in a seated leg press. | At baseline, 1 month, 5 months (at study completion) | 
| Armflexion Test: | Measures of overall strength in the upper extremities. The number of times the participant can inflect the elbow with dumbbell is measured in 30 sec. | At baseline, 1 month, 5 months (at study completion) | 
| 2-minute knee lift test: | Measures aerobic capacity in the elderly. Number of high knee lifts in 2 minutes. | At baseline, 1 month, 5 months (at study completion) | 
| 2,45minute up-and-go test: | Target for basic mobility in the elderly. Time it takes to rise from a chair, walk around a cone 2,45m away, go back and sit down again. Moderate to good correlation between the corresponding 3m test and Berg Balance Scale (r = 0.81), walking speed (r = 0.61) and Barthel index (r = 0.78) and a good test-retest- reliability (ICC = 0.98). | At baseline, 1 month, 5 months (at study completion) | 
| DXA scan | Lean body mass. Measurement of fat and fat-free mass and total bone mass (BMC). Executed only at baseline and at study end. | At baseline, 1 month, 5 months (at study completion) | 
| Bone Mineral Density | Of the spine, distal forearm bilaterally, total hip bilaterally and in the skeleton as a whole (total body). In case of osteoporosis treatment will be initiated following the department's usual guidelines, which can blur the results for bone density. | At baseline, 1 month, 5 months (at study completion | 
| Major Depression Inventory (MDI): | Questionnaire on depression and mental well-being. | At baseline, 1 month, 5 months (at study completion) | 
| Montreal Cognitive Assessment (MoCA): | A cognitive screening test that provides an estimate of the intellectual functioning; This test is also sensitive to mild cognitive problems and dementia. | At baseline, 1 month, 5 months (at study completion) | 
| Quality of Life EQ-5D: | Questionnaire on the experienced quality of life. | At baseline, 1 month, 5 months (at study completion) | 
| Modified PISQ-12: | An assessment of sexual performance (potency) and sexual desire. There are previously found improved sexual function, mood, muscle strength and body composiAn evaluation questionnaire of sexual function | At baseline, 1 month, 5 months (at study completion) | 
| Aastrands Test: | Sub-maximal fitness test performed on a treadmill. Includes monitoring heart rate | At baseline, 1 month, 5 months (at study completion) | 
| Measurements of the Heart Rate Variability (HRV) | Studies have indicated that hypogonodal men can improve the Heart Rate Variability by testosterone treatment | At baseline, 1 month, 5 months (at study completion) | 
| Dual-energy X-ray absorptiometry | Measurement of the body composition bioimpedance. | At baseline, 1 month, 5 months (at study completion) | 
| Safety parameters - blood pressure | Blood pressure. Blood samples: Serum testosterone, hemoglobin, hematocrit, lipid profile, Potassium, Natrium, creatinine, CRP, AST, bilirubin, alkaline phosphatase, TSH, p-ionized calcium, PTH, Ca ++, and 25-OH vitamin D. | Measured every four weeks through the study (for 5 months) | 
| Side effects | Measuring a lot of posssible side effects to training and testosterone | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - testosterone level | Measuring levels of testosterone and safely parameter | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - hemoglobin level | Measuring levels hemoglobin | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - hematocrit level | Measuring levels of hematocrit | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - lipid profile | Measuring levels cholesterol | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - Potassium | Measuring levels of potassium | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - Natrium | Measuring levels of natrium | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - creatinine | Measuring levels of creatinine | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - CRP | Measuring levels of CRP | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - Aspartate aminotransferase (AST) | Measuring levels of aspartate aminotransferase (AST) | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - bilirubin | Measuring levels of bilirubin | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - alkaline phosphatase | Measuring levels of alkaline phosphatase | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - Thyreoid Stimulating Hormone (TSH) | Measuring levels of TSH | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - p-ionized calcium | Measuring levels of p-ionized calcium | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - PTH | Measuring levels of PTH | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - Ca ++ | Measuring levels of Ca2+ | Measured every four weeks through the study (for 5 months) | 
| Safety parameters - blood sample - 25-OH vitamin D. | Measuring levels of vitamin D | Measured every four weeks through the study (for 5 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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older, frail, men, progressive muscle training, muscle training, exercise, testosterone