Strength Training as a Supplemental Therapy of Androgen Deficiency of the Aging Male

Study Overview
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Brief Summary
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This study examines the effect of 12-week strength training program with and without testosterone replacement therapy (TRT) on body composition, physical function, selected biochemical markers of metabolic health, molecular parameters of training adaptation and the quality of life patients with ADAM. The investigators believe, that strength training program performed 2 times per week for 12 weeks can improve body composition (decrease fat mass and gain lean mass), muscle strength, muscle power and general quality of life in all training groups. In addition, combination TRT and strength training could help decrease fat mass, improve BMI, cardio-respiratory fitness and thus provide optimal therapy combination for hypogonadal ageing males.

Detailed Description
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The study is 3 groups controlled 12-week study to assess the effect of testosterone replacement therapy (TRT) with strength training (ST) and strength training (ST) for hypogonadal participants without testosterone replacement therapy (NON-TRT) with control healthy eugonadal group, that is also engaged in strength training. Strength training protocol starts one week after all the pre-intervention testing. The intervention is performed at the Comenius University in Bratislava, Faculty of Physical Education and Sport (FSPORT CU) in Slovakia. The strength training protocol follows a modified resistance exercise program. The participants perform strength training sessions two times per week for 12 weeks. All training sessions are supervised and guided by professional coaches with university degree in sports training to ensure safety, technique and progression in training load, with a maximum of three participants per coach. Each training session include 5-minute general dynamic warm-up followed by progressive strength training with exercises for the entire body. The strength exercises are performed with free weights and on machines. The training program consist of 6 exercises for upper and lower body at an intensity of 60-80% (8 - 12RM: the load that induces technique failure in eight or twelve repetitions) of one-repetition maximum and takes approximately 60 minutes. The participants are instructed to perform concentric action in 2 s and immediately after eccentric action in also 2 s. The exercises performed are: leg press, split squats, bench press, knee extension, knee flexion, seated cable rows, seated cable pull downs, dumbbell bench press, incline dumbbell bench press. Training equipment is provided by KOHI Leopoldov, Slovakia and Technogym, Italia. Clinical and muscle cellular outcomes are collected before the intervention (pre-testing assessments) and after the intervention (post-testing assessments). Post intervention measurements start 7 days after intervention and go up to 3 weeks after intervention. Clinical outcomes Body composition analysis is measured by Dual-energy X-ray Absorptiometry using Hologic fan-beam bone densitometer Discovery QDR series. LBM(lean body mass) is measured in total body and separately for arms, legs and trunk. The changes in lower and upper body LBM are investigated separately because of differences in androgen sensitivity in leg muscles compared to neck, chest and shoulder muscles. Body weight is measured by bioimpedance scale, the height by stadiometer and waist circumference by tape. The body mass index is calculated. Biochemical outcomes Fasting morning venous blood is taken from 8:00 am to 10:00 am. The haematological and biochemical parameters analysed are Haemoglobin, hematocrits, leucocytes, thrombocytes, glucose, urea, sodium, potassium, calcium, ALAT, total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, testosterone, oestrogen, LH, FSH, SHBG, albumin, bilirubin, total protein, CRP, insulin, PSA. Physical functioning Muscle strength is measured by novel portable isometric knee dynamometer (maximal voluntary contraction of isometric knee extension, isometric knee flexion), hand grip strength dynamometry by Camry Digital Hand Dynamometer, predicted 1RM leg press from multiple repetition maximum testing. Cardio-respiratory fitness is measured by The Single Stage Treadmill Walking Test on Woodway Pro Treadmill, 10-m fast walk and 10-m usual walk measured by Photocells. Quality of life The general health status is measured by The Short Form (36) Health Survey patient-reported survey of patient health (SF-36). In addition to that clinically investigating the health-related quality of life (HRQoL) and symptoms of aging men are measured by Aging Males' Symptom Scale (AMS). Muscle cellular outcomes Muscle biopsies are obtain from approximately 80% of the subjects included in the study. Participants not willing to undergo biopsy are still eligible for trial participation. With the participant in a supine position, a 5 mm Muscle Biopsy Cannula (Bergstrom-stille, Sweden) with manual suction is used to obtain muscle samples (200 mg), under local anaesthesia (Lidocain 2%,). Before the intervention the biopsy is obtained from the mid-section of the right musculus vastus lateralis, and after the intervention the biopsy is obtained 3 cm proximal to the pre-intervention biopsy.

Official Title
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Strength Training as a Supplemental Therapy of Androgen Deficiency of the Aging Male (ADAM)

Conditions
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Hypogonadism, Male, Physical Activity, Testosterone Deficiency

Intervention / Treatment
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* Procedure: Strength training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of secondary hypogonadism on testosterone replacement therapy, newly diagnosed patients of secondary hypogonadism. Exclusion Criteria: Regular strength training, medical treating osteoporosis, abnormal digital rectal results, conditions which are medical contraindications (without adjusting state): diabetes mellitus, severe cardiac arrhythmia, uncontrolled hypertension, unstable angina pectoris, chronic obstructive pulmonary disease, epilepsy, unstable bone lesions with high risk of fracture, prostate cancer or abnormal serum PSA levels without adverse histological examination.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 60 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study is 3 arms 12-week strength training program to assess the effect of testosterone replacement therapy (TRT) with strength training (ST) and strength training (ST) for hypogonadal patients without testosterone replacement therapy (NON-TRT) with control healthy eugonadal group, that is also engaged in strength training.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hypogonadal males without TRT<br>Strength training | Procedure: Strength training<br>* The participants perform strength training sessions two times per week for 12 weeks. Each training session include 5-minute general dynamic warm-up followed by progressive strength training with exercises for the entire body. The strength exercises are performed with free weights and on machines. The training program consist of 6 exercises for upper and lower body at an intensity of 60-80% (8 - 12RM: the load that induces technique failure in eight or twelve repetitions) of one-repetition maximum and takes approximately 60 minutes. The exercises performed are: leg press, split squats, bench press, knee extension, knee flexion, seated cable rows, seated cable pull downs, dumbbell bench press, incline dumbbell bench press.<br>|
| Experimental: hypogonadal males with TRT<br>Strength training and regular prescribed testosterone therapy given by participant urologist. | Procedure: Strength training<br>* The participants perform strength training sessions two times per week for 12 weeks. Each training session include 5-minute general dynamic warm-up followed by progressive strength training with exercises for the entire body. The strength exercises are performed with free weights and on machines. The training program consist of 6 exercises for upper and lower body at an intensity of 60-80% (8 - 12RM: the load that induces technique failure in eight or twelve repetitions) of one-repetition maximum and takes approximately 60 minutes. The exercises performed are: leg press, split squats, bench press, knee extension, knee flexion, seated cable rows, seated cable pull downs, dumbbell bench press, incline dumbbell bench press.<br>|
| Active Comparator: healthy eugonadal males<br>Strength training | Procedure: Strength training<br>* The participants perform strength training sessions two times per week for 12 weeks. Each training session include 5-minute general dynamic warm-up followed by progressive strength training with exercises for the entire body. The strength exercises are performed with free weights and on machines. The training program consist of 6 exercises for upper and lower body at an intensity of 60-80% (8 - 12RM: the load that induces technique failure in eight or twelve repetitions) of one-repetition maximum and takes approximately 60 minutes. The exercises performed are: leg press, split squats, bench press, knee extension, knee flexion, seated cable rows, seated cable pull downs, dumbbell bench press, incline dumbbell bench press.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Lean Mass | Total body by Dual-energy X-ray Absorptiometry using Hologic fan-beam bone densitometer Discovery QDR series. | 7 days before intervention, 7 days after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fat Mass | Total body by Dual-energy X-ray Absorptiometry using Hologic fan-beam bone densitometer Discovery QDR series. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Total Body Mass | Total body by Dual-energy X-ray Absorptiometry using Hologic fan-beam bone densitometer Discovery QDR series. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in 10-m Usual Walk Test | Measured in seconds by Microgates Photocells and than calculated to meters per second. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in 10-m Fast Walk Test | Measured in seconds by Microgates Photocells than calculated to meters per second | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Handgrip Strength | Measured by Camry Digital Hand Dynamometer. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Maximal Voluntary Contraction (MVC) of Isometric Knee Extension | Measured by Portable Isometric Knee Dynamometer. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Maximal Voluntary Contraction (MVC) of Isometric Knee Flexion | Measured by Portable Isometric Knee Dynamometer. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in The Single Stage Treadmill Walking Test | This test is focused on calculated VO2max in ml.kg-1.min-1 from speed measured on Woodway Pro Treadmill. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Predicted One Repetition Maximum on Leg Press | One repetition maximum in kg on leg press is predicted from multiple repetition maximum testing and measured on Life Fitness Signature Series Leg Press machine. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Maximal Voluntary Contraction in Benchpress | Measured in N by FiTRO Force Plates. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in The Short Form Health Survey (SF-36) | Patient-reported survey of patient health (SF-36), clinically investigating the health-related quality of life (HRQoL). The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The items contributing to a scale are scored so that a higher score represents better health, and they are averaged together to create the scale score. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Aging Males' Symptom (AMS) Scale | Measuring symptoms of ageing men by numeric score scale. The questionnaire has for each of the 17 item an option to check one of 5 degrees of severity (severity 1...5 points at the questionnaire). The composite scores for each of the three dimensions (sub-scales) is based on adding up the scores of the items of the respective dimensions. The composite score (total score) is the sum of the three dimension scores. Higher score means higher severity of symptoms. The minimum total score is 17 and the maximum is 85. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Metabolic Parameters | Fasting morning venous blood was taken after overnight (10-hour) fasting and 15 min rest from cubital vein from 8:00 am to 10:00 am [69] into closed system collection tubes containing beads coated with a clotting activator and polyacryl ester-gel (Sarstedt AG & Co, Germany). The blood will be centrifuged (3000g, 4°C, 10min) immediately after sampling to obtain EDTA plasma or they will be centrifuged (3000g, 4°C, 20min) after 30min at RT, to obtain serum. | 7 days before intervention, 7 days after intervention | 
| Change From Baseline in Liver Function Blood Parameters | Fasting morning venous blood was taken after overnight (10-hour) fasting and 15 min rest from cubital vein from 8:00 am to 10:00 am [69] into closed system collection tubes containing beads coated with a clotting activator and polyacryl ester-gel (Sarstedt AG & Co, Germany). The blood will be centrifuged (3000g, 4°C, 10min) immediately after sampling to obtain EDTA plasma or they will be centrifuged (3000g, 4°C, 20min) after 30min at RT, to obtain serum. | 7 days before intervention, 14 days after intervention | 
| Change From Baseline in Hormonal Parameters | Fasting morning venous blood was taken after overnight (10-hour) fasting and 15 min rest from cubital vein from 8:00 am to 10:00 am [69] into closed system collection tubes containing beads coated with a clotting activator and polyacryl ester-gel (Sarstedt AG & Co, Germany). The blood will be centrifuged (3000g, 4°C, 10min) immediately after sampling to obtain EDTA plasma or they will be centrifuged (3000g, 4°C, 20min) after 30min at RT, to obtain serum. | 7 days before intervention, 14 days after intervention | 
| Change From Baseline in Ions | Fasting morning venous blood was taken after overnight (10-hour) fasting and 15 min rest from cubital vein from 8:00 am to 10:00 am [69] into closed system collection tubes containing beads coated with a clotting activator and polyacryl ester-gel (Sarstedt AG & Co, Germany). The blood will be centrifuged (3000g, 4°C, 10min) immediately after sampling to obtain EDTA plasma or they will be centrifuged (3000g, 4°C, 20min) after 30min at RT, to obtain serum. | 7 days before intervention, 14 days after intervention | 
| Change From Baseline in CRP | Fasting morning venous blood was taken after overnight (10-hour) fasting and 15 min rest from cubital vein from 8:00 am to 10:00 am [69] into closed system collection tubes containing beads coated with a clotting activator and polyacryl ester-gel (Sarstedt AG & Co, Germany). The blood will be centrifuged (3000g, 4°C, 10min) immediately after sampling to obtain EDTA plasma or they will be centrifuged (3000g, 4°C, 20min) after 30min at RT, to obtain serum. | 7 days before intervention, 14 days after intervention | 
| Change From Baseline in Muscle Fiber Size | Muscle fiber size measured in um2. Analysis of the date are in progress. | 7 days before intervention, 14 days after intervention | 
| Change From Baseline in Regulators of Muscle Fiber Size | Regulators of muscle fiber size - number of myonuclei per muscle fiber, number of satellite cells per muscle fiber, number of satellite cells and myonuclei positive for androgen receptors, proteins involved in muscle hypertrophy. Analysis of the date are in progress. | 7 days before intervention, 14 days after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypogonadism, aging male, strength training, physical activity, testosterone