Clinical trial NCT02873559: Effect of PROGRESSive Training and Teststerone in Older Frail Men
Official title: Effect of PROGRESSive Resistance Training, Protein Supplements and Testosterone in Older Frail Men With Testosterone Deficiency (PROGRESS Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Muscle Weakness
Keywords: older
frail
men
progressive muscle training
muscle training
exercise
testosterone
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2016-08-19
Enrollment: 192
Sex: MALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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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.

Primary outcomes:
measure: Stand-up-and Sit-test
timeFrame: up to 5 months (at study completion)
Secondary outcomes:
measure: Frequency and severity of falls via questionaire
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Balance ability,
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Avlund mobility scale
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Leg extensor Power Rig test
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Isometric muscle strength
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Armflexion Test:
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: 2-minute knee lift test:
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: 2,45minute up-and-go test:
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: DXA scan
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Bone Mineral Density
timeFrame: At baseline, 1 month, 5 months (at study completion
measure: Major Depression Inventory (MDI):
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Montreal Cognitive Assessment (MoCA):
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Quality of Life EQ-5D:
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Modified PISQ-12:
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Aastrands Test:
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Measurements of the Heart Rate Variability (HRV)
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Dual-energy X-ray absorptiometry
timeFrame: At baseline, 1 month, 5 months (at study completion)
measure: Safety parameters - blood pressure
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Side effects
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - testosterone level
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - hemoglobin level
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - hematocrit level
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - lipid profile
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - Potassium
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - Natrium
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - creatinine
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - CRP
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - Aspartate aminotransferase (AST)
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - bilirubin
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - alkaline phosphatase
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - Thyreoid Stimulating Hormone (TSH)
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - p-ionized calcium
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - PTH
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - Ca ++
timeFrame: Measured every four weeks through the study (for 5 months)
measure: Safety parameters - blood sample - 25-OH vitamin D.
timeFrame: Measured every four weeks through the study (for 5 months)
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Karsten Overgaard
state: Danmark
city: Herlev
country: Denmark
facility: Medical Dept. O, Geriatric Section
Study officials:
affiliation: Herlev Hospital, Neurological Department N108
name: Karsten Overgaard, M.D.
role: STUDY_DIRECTOR
References:
citation: Rasmussen R, Midttun M, Kolenda T, Ragle AM, Sorensen TW, Vinther A, Zerahn B, Pedersen M, Overgaard K. Therapist-Assisted Progressive Resistance Training, Protein Supplements, and Testosterone Injections in Frail Older Men with Testosterone Deficiency: Protocol for a Randomized Placebo-Controlled Trial. JMIR Res Protoc. 2018 Mar 2;7(3):e71. doi: 10.2196/resprot.8854.