Clinical trial NCT03282682: Strength Training as a Supplemental Therapy of Androgen Deficiency of the Aging Male
Official title: Strength Training as a Supplemental Therapy of Androgen Deficiency of the Aging Male (ADAM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypogonadism, Male
Physical Activity
Testosterone Deficiency
Keywords: hypogonadism
aging male
strength training
physical activity
testosterone
Lead sponsor: Comenius University
Sponsor class: OTHER
Collaborators: name: Norwegian School of Sport Sciences
name: Slovak Academy of Sciences
First posted: 2017-09-14
Enrollment: 22
Sex: MALE
Minimum age (years): 45
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Lean Mass
timeFrame: 7 days before intervention, 7 days after intervention
Secondary outcomes:
measure: Change From Baseline in Fat Mass
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Total Body Mass
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in 10-m Usual Walk Test
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in 10-m Fast Walk Test
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Handgrip Strength
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Maximal Voluntary Contraction (MVC) of Isometric Knee Extension
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Maximal Voluntary Contraction (MVC) of Isometric Knee Flexion
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in The Single Stage Treadmill Walking Test
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Predicted One Repetition Maximum on Leg Press
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Maximal Voluntary Contraction in Benchpress
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in The Short Form Health Survey (SF-36)
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Aging Males' Symptom (AMS) Scale
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Metabolic Parameters
timeFrame: 7 days before intervention, 7 days after intervention
measure: Change From Baseline in Liver Function Blood Parameters
timeFrame: 7 days before intervention, 14 days after intervention
measure: Change From Baseline in Hormonal Parameters
timeFrame: 7 days before intervention, 14 days after intervention
measure: Change From Baseline in Ions
timeFrame: 7 days before intervention, 14 days after intervention
measure: Change From Baseline in CRP
timeFrame: 7 days before intervention, 14 days after intervention
measure: Change From Baseline in Muscle Fiber Size
timeFrame: 7 days before intervention, 14 days after intervention
measure: Change From Baseline in Regulators of Muscle Fiber Size
timeFrame: 7 days before intervention, 14 days after intervention
Other outcomes:
Locations:
city: Bratislava
country: Slovakia
facility: Comenius University in Bratislava, Faculty of physical education and sport
Study officials:
affiliation: Comenius University of Bratislava, Faculty Physical Education and Sport
name: Milan Sedliak, assoc. prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Basaria S. Androgen deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth. J Androl. 2008 Sep-Oct;29(5):534-9. doi: 10.2164/jandrol.108.005454. Epub 2008 Jun 20.
citation: Hildreth KL, Barry DW, Moreau KL, Vande Griend J, Meacham RB, Nakamura T, Wolfe P, Kohrt WM, Ruscin JM, Kittelson J, Cress ME, Ballard R, Schwartz RS. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab. 2013 May;98(5):1891-900. doi: 10.1210/jc.2013-2227. Epub 2013 Mar 26.
citation: Schwarz ER, Willix RD Jr. Impact of a physician-supervised exercise-nutrition program with testosterone substitution in partial androgen-deficient middle-aged obese men. J Geriatr Cardiol. 2011 Dec;8(4):201-6. doi: 10.3724/SP.J.1263.2011.00201.
citation: Kadi F, Bonnerud P, Eriksson A, Thornell LE. The expression of androgen receptors in human neck and limb muscles: effects of training and self-administration of androgenic-anabolic steroids. Histochem Cell Biol. 2000 Jan;113(1):25-9. doi: 10.1007/s004180050003.
citation: Gardner JR, Livingston PM, Fraser SF. Effects of exercise on treatment-related adverse effects for patients with prostate cancer receiving androgen-deprivation therapy: a systematic review. J Clin Oncol. 2014 Feb 1;32(4):335-46. doi: 10.1200/JCO.2013.49.5523. Epub 2013 Dec 16.
citation: Kralik M, Cvecka J, Buzgo G, Putala M, Ukropcova B, Ukropec J, Killinger Z, Payer J, Kollarik B, Bujdak P, Raastad T, Sedliak M. Strength training as a supplemental therapy for androgen deficiency of the aging male (ADAM): study protocol for a three-arm clinical trial. BMJ Open. 2019 Sep 5;9(9):e025991. doi: 10.1136/bmjopen-2018-025991.