Falls (Accidents) in Old Age, Frail Elderly Patients, Hypogonadal Males, Testosterone Replacement Therapy
Conditions
Keywords
hypogonadism, frailty, falls, testosterone replacement therapy
Brief summary
The purpose of this study is to increase the functional level of the elderly to thereby reduce fall risk, improve motor skills, and increase psychological well-being, as well as to assess whether the restoration of a normal testosterone level contributes to a faster recovery. The effect of testosterone is investigated as measured by physical and mental functional capacity, including cognition, in hypogonadal elderly men with a significant loss of function. The study is aimed at participants who are too weak to participate in the progressive strength training.
Detailed description
Please see the uploaded study protocol.
Interventions
Testosterone supplementation is given intramuscularly with 1000 mg testosterone undecanoate, which has an effect for approx. 12 weeks, but which can be repeated more frequently between the 1st and 2nd administration. The injection is thus repeated in week 6. 3 injections per trial subject are expected, i.e., in weeks 1, 6, and 16. If the participants are motivated to continue so that long-term effects can be measured, the participants will be asked in week 12 whether they wish to continue to week 52. Upon acceptance of continuation to week 52, testosterone and placebo injections are offered according to original groups in weeks 26, 36, and 46, after which testing of primary and secondary endpoints is not only performed in week 20 but also in week 52.
Sponsors
Rune Skovgaard Rasmussen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Treatment with testosterone is made double-blind. We will ensure that the persons evaluating a patient do not have knowledge of the patient's treatment group.
Intervention model description
Participants are randomized equally into 2 different treatment groups with 48 participants each: 1. A control group given 3 placebo injections 2. A testosterone group given 3 testosterone injections. Randomization is thus into two arms so that the effect of testosterone can be evaluated against placebo.
Eligibility
Sex/Gender
MALE
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men aged 70 or over. * Living at home in their own home or in sheltered housing. * Independent walking function, possibly with a walking aid. * Able to perform the chair-stand test a maximum of 8 times in 30 seconds or Timed Up and Go (TUG) of at least 30 seconds. * There must be at least 3 symptoms of frailty or objective findings. * Serum testosterone \< 10 nmol/L as an average of 2 independent measurements at the Center for Growth and Reproduction, Rigshospitalet.
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 prostate size in cubic centimeters (cc)). * Hemochromatosis. * Heart diseases in the form of: Peri-, myo-, or endocarditis, angina pectoris, severe heart failure (NYHA class III and IV), severe hypertension (systolic BP \> 180 or diastolic BP \> 105 mmHg after possible antihypertensive treatment). - Resting dyspnea. * Liver (ASAT \> 2 x upper normal limit) or renal insufficiency (serum creatinine \> 200 micromol/l). * Severe intractable epilepsy or migraine. * Insulin treatment. * Previous or current bisphosphonate, fluoride, HRT, SERM, strontium, teriparatide, or more than 3 weeks of prednisolone treatment. * Joint disease with acute inflammation. * Active cancer disease, in chemo- or radiotherapy. * Bone metabolic disease except for 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, Y chromosome deletions, other sex chromosome abnormalities. * Significant abuse, mental illness, dementia, physical handicaps with inability to complete the intervention or tests, or to give informed consent. * Contraindications for testosterone undecanoate are thus included in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Chair-stand test | At weeks 0, 4 and 20. | A measure of general strength in extremities. Number of times the participant can stand up and sit down from a chair in 30 seconds. A good correlation (r=0.78) has been found with leg press and acceptable test-retest reliability (ICC=0.86). It has recently been scientifically documented that the ability among elderly persons to perform this simple test correlates with the risk of serious fall accidents |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of fall frequency and severity | At weeks 0, 4 and 20. | Registered via a questionnaire for each trial subject and is also included in the monitoring of adverse events. |
| Balance ability | At weeks 0, 4 and 20. | Tested via the Tandem test, which contains three starting positions: 1) Standing with feet together, standing in semi-tandem stance, and standing in tandem stance. |
| Avlund's mobility scale | At weeks 0, 4 and 20. | Questions about experiencing fatigue and need for support in common activities of daily living. Avlund's mobility scale is correlated with isometric muscle strength, simple functional tests, increased risk of hospitalizations, and mortality. Good inter- and intra-reliability (kappa 0.72-1.00) has been shown. Scores range from 0 to 6, and higher scores indicate worse outcome. |
| Geriatric Depression Scale (GDS) | At weeks 0, 4 and 20. | Questionnaire about depression and psychological well-being. Scores range from 0 til 15. Score below 5 are normal, while scores of 5 or higher indicate varying degrees of depression, scoring 13-15 indicates severe depression. |
| Montreal Cognitive Assessment (MoCA) | At weeks 0, 4 and 20. | The Montreal Cognitive Assessment is a cognitive screening instrument which provides an estimate of the level of intellectual functioning. Scores are from 0 to 30, where a score of 26 or higher is considered normal. Montreal Cognitive Assessment is moreover sensitive to mild cognitive problems as well as dementia. Studies have shown that Montreal Cognitive Assessment is more sensitive than Mini Mental State Examination to detecting mild cognitive changes and is as effective in identifying the incidence of Alzheimer's disease. |
| Mini Mental State Examination (MMSE) | At weeks 0, 4 and 20. | Cognitive screening test that provides an estimate of the intellectual functional level. This test is included as it is performed as standard at the Geriatric Outpatient Clinic. Combined, MMSE and MoCA provide a broader assessment of cognitive functional level. Scores range from 0 to 30, higher scores indicate better cognitive status. Scores from 26 to 30 are considered normal. |
| Quality of life EQ-5D | At weeks 0, 4 and 20. | Questionnaire about perceived quality of life. Scores range from 0 to 1 (first scale) and from 0 to 100 (second scale). Higher scores indicate better quality of life. |
| Clinical Frailty Scale (CFS) | At weeks 0, 4 and 20. | General assessment of health and functional level in the elderly. Scoring ranges from 1 to 9, and higher scores indicate more frailty. |
| Falls Efficacy Scale - International (FES-I, Fear of falling). Scores range from 16 to 64, and higher scores indicate increased anxiety of having a severe fall accident. | At weeks 0, 4 and 20. | Assessment of fall risk in the elderly. |
Countries
Denmark
Contacts
CONTACTRune S. Rasmussen, MSc, PhD
CONTACTKarsten Overgaard, MD, Neurologist
PRINCIPAL_INVESTIGATORMette Midttun, MD, DMSc
Holbaek Sygehus
Outcome results
None listed