Effect of PROGRESSive Training and Teststerone in Older Frail Men (PROGRESS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Muscle Weakness
• Intervention / Treatment: Drug: testosterone; Other: Progressive muscle training

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 Type: Interventional
• Enrollment (Anticipated): 196
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Karsten Overgaard, M.D.; Phone Number: +45 2617 2611; Email: karstenovergaard20@hotmail.com
• Study Contact Backup: Name: Rune S. Rasmussen, MA, PhD; Phone Number: +45 2875 7500; Email: rsr@sund.ku.dk

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Recruiting
    • Medical Dept. O, Geriatric Section
    • Contact: Mette Midttun, MD, DMSc; Phone Number: +45 38689188; Email: mette.midttun@regionh.dk
    • Principal Investigator: Mette Midttun, MD, DMSc
  • Danmark
    • Hellerup, Danmark, Denmark, DK-2900
      • Recruiting
      • Karsten Overgaard
      • Contact: Karsten Overgaard, neurologist; Phone Number: +45 2617 2611; Email: karstenovergaard20@hotmail.com
      • Contact: Rune Rasmussen, PhD neuropsy; Phone Number: +45 2875 7500; Email: rsr@sund.ku.dk
      • Principal Investigator: Mette Midttun, M.D. DMSci

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Controls; A control group, which is 20 weeks with placebo injections without training.
EXPERIMENTAL: Testosterone; A testosterone group given 20 weeks on testosterone injections without training	Drug: testosterone; Testosterone supplemented in 5 months
EXPERIMENTAL: 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	Other: Progressive muscle training; Progressive muscle training during 4 months; Other Names: Training
EXPERIMENTAL: Testosterone and 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	Drug: testosterone; Testosterone supplemented in 5 months; Other: Progressive muscle training; Progressive muscle training during 4 months; Other Names: Training

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Study Director: Karsten Overgaard, M.D., Herlev Hospital, Neurological Department N108

Publications and helpful links

General Publications

• 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.

Helpful Links

• Therapist-Assisted Progressive Resistance Training, Protein Supplements, and Testosterone Injections in Frail Older Men with Testosterone Deficiency: Protocol for a Randomized Placebo-Controlled Trial
• Testosterone serum levels in elderly fall-prone men do not correlate with age or performance in the 30 seconds chair stand test

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ANTICIPATED): December 31, 2021
• Study Completion (ANTICIPATED): January 1, 2022

Study Registration Dates

• First Submitted: August 12, 2016
• First Submitted That Met QC Criteria: August 18, 2016
• First Posted (ESTIMATE): August 19, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 30, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: exercise; men; testosterone; older; frail; muscle training; progressive muscle training
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: Ethical protocol H-16020521

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO