Effect of PROGRESSive Training and Teststerone in Older Frail Men

Phase 2

Completed

• Conditions: Muscle Weakness
• Interventions: Drug: testosterone; Other: Progressive muscle training

• Registration Number: NCT02873559
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-08-12
• Study First Submitted QC: 2016-08-18
• Study First Posted: 2016-08-19
• Study Start: 2016-11-01
• Primary Completion: 2022-03-31
• Study Completion: 2023-03
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-28
• Last Update Posted: 2024-05-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 192

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Testosterone	testosterone	A testosterone group given 20 weeks on testosterone injections without training
Training	Progressive muscle training	A Training Group, which is 20 weeks with placebo injections and 16 weeks of progressive resistance training supplemented with vitamin D and protein supplements
Testosterone and training	testosterone	A combination group that is 20 weeks with testosterone injections and 16 weeks of progressive resistance training supplemented with vitamin D and protein supplements
Testosterone and training	Progressive muscle training	A combination group that is 20 weeks with testosterone injections and 16 weeks of progressive resistance training supplemented with vitamin D and protein supplements

Primary Outcome Measures

Name	Time	Method
Stand-up-and Sit-test	up to 5 months (at study completion)	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).

Secondary Outcome Measures

Name	Time	Method
Safety parameters - blood sample - Ca ++	Measured every four weeks through the study (for 5 months)	Measuring levels of Ca2+
Safety parameters - blood sample - 25-OH vitamin D.	Measured every four weeks through the study (for 5 months)	Measuring levels of vitamin D
Balance ability,	At baseline, 1 month, 5 months (at study completion)	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.
Frequency and severity of falls via questionaire	At baseline, 1 month, 5 months (at study completion)	included in the monitoring of adverse events.
Avlund mobility scale	At baseline, 1 month, 5 months (at study completion)	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
Leg extensor Power Rig test	At baseline, 1 month, 5 months (at study completion)	An instrument for measuring muscle strength in the lower extremities.
Isometric muscle strength	At baseline, 1 month, 5 months (at study completion)	Measurement of isometric muscle strength m. quadriceps in a seated leg press.
Armflexion Test:	At baseline, 1 month, 5 months (at study completion)	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.
2-minute knee lift test:	At baseline, 1 month, 5 months (at study completion)	Measures aerobic capacity in the elderly. Number of high knee lifts in 2 minutes.
2,45minute up-and-go test:	At baseline, 1 month, 5 months (at study completion)	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).
DXA scan	At baseline, 1 month, 5 months (at study completion)	Lean body mass. Measurement of fat and fat-free mass and total bone mass (BMC). Executed only at baseline and at study end.
Bone Mineral Density	At baseline, 1 month, 5 months (at study completion	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.
Major Depression Inventory (MDI):	At baseline, 1 month, 5 months (at study completion)	Questionnaire on depression and mental well-being.
Montreal Cognitive Assessment (MoCA):	At baseline, 1 month, 5 months (at study completion)	A cognitive screening test that provides an estimate of the intellectual functioning; This test is also sensitive to mild cognitive problems and dementia.
Quality of Life EQ-5D:	At baseline, 1 month, 5 months (at study completion)	Questionnaire on the experienced quality of life.
Modified PISQ-12:	At baseline, 1 month, 5 months (at study completion)	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
Aastrands Test:	At baseline, 1 month, 5 months (at study completion)	Sub-maximal fitness test performed on a treadmill. Includes monitoring heart rate
Measurements of the Heart Rate Variability (HRV)	At baseline, 1 month, 5 months (at study completion)	Studies have indicated that hypogonodal men can improve the Heart Rate Variability by testosterone treatment
Dual-energy X-ray absorptiometry	At baseline, 1 month, 5 months (at study completion)	Measurement of the body composition bioimpedance.
Safety parameters - blood pressure	Measured every four weeks through the study (for 5 months)	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.
Side effects	Measured every four weeks through the study (for 5 months)	Measuring a lot of posssible side effects to training and testosterone
Safety parameters - blood sample - testosterone level	Measured every four weeks through the study (for 5 months)	Measuring levels of testosterone and safely parameter
Safety parameters - blood sample - hemoglobin level	Measured every four weeks through the study (for 5 months)	Measuring levels hemoglobin
Safety parameters - blood sample - hematocrit level	Measured every four weeks through the study (for 5 months)	Measuring levels of hematocrit
Safety parameters - blood sample - lipid profile	Measured every four weeks through the study (for 5 months)	Measuring levels cholesterol
Safety parameters - blood sample - Potassium	Measured every four weeks through the study (for 5 months)	Measuring levels of potassium
Safety parameters - blood sample - Natrium	Measured every four weeks through the study (for 5 months)	Measuring levels of natrium
Safety parameters - blood sample - creatinine	Measured every four weeks through the study (for 5 months)	Measuring levels of creatinine
Safety parameters - blood sample - CRP	Measured every four weeks through the study (for 5 months)	Measuring levels of CRP
Safety parameters - blood sample - Aspartate aminotransferase (AST)	Measured every four weeks through the study (for 5 months)	Measuring levels of aspartate aminotransferase (AST)
Safety parameters - blood sample - bilirubin	Measured every four weeks through the study (for 5 months)	Measuring levels of bilirubin
Safety parameters - blood sample - alkaline phosphatase	Measured every four weeks through the study (for 5 months)	Measuring levels of alkaline phosphatase
Safety parameters - blood sample - Thyreoid Stimulating Hormone (TSH)	Measured every four weeks through the study (for 5 months)	Measuring levels of TSH
Safety parameters - blood sample - p-ionized calcium	Measured every four weeks through the study (for 5 months)	Measuring levels of p-ionized calcium
Safety parameters - blood sample - PTH	Measured every four weeks through the study (for 5 months)	Measuring levels of PTH

Trial Locations

Locations (2)

Karsten Overgaard; 🇩🇰 Hellerup, Danmark, Denmark

Medical Dept. O, Geriatric Section; 🇩🇰 Herlev, Denmark