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Systemic Hormones and Muscle Protein Synthesis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03054168
Recruitment Status : Active, not recruiting
First Posted : February 15, 2017
Last Update Posted : February 26, 2019
Sponsor:
Information provided by (Responsible Party):
Philip Atherton, University of Nottingham

Brief Summary:
This study evaluates the effect of increase in testosterone levels in older males and the effects of decrease in testosterone levels in young males on muscle protein synthesis.

Condition or disease Intervention/treatment Phase
Sarcopenia Muscle Hypotrophy Muscle Atrophy Drug: Sustanon 250 Drug: Zoladex Other: Placebo Phase 3

Detailed Description:

Skeletal muscle represents the largest organ in the body, comprising >50% of total body mass. The function of skeletal muscle is best understood for its role in locomotion and providing mechanical support to the skeleton to facilitate movement. However, skeletal muscles are also important for maintaining whole-body metabolic health. For example, muscles also act as a site for glucose disposal thereby acting to maintain whole-body glycaemic control. In addition, skeletal muscles represent a vast protein store, the amino acids from which can be used in times of fasting, infection and disease to provide energy to maintain other critical organs. Exercise (resistance type exercise (RE-T) in particular) still remains the most effective means by which to maintain and increase muscle mass through stimulation of muscle protein synthesis (MPS), despite this, how exercise regulates these changes in muscle mass is still unknown. A number of pathways have been inferred as key, however it is clear from a number of studies that systemic hormone levels, testosterone in particular, may provide a significant contribution. It is well known that chronic androgenic hormone deficiency can lead to a loss of lean body mass and strength, which can in turn contribute to impaired physical function. Furthermore, when testosterone levels are pharmacologically reduced (using a gonadotropin releasing hormone analogue) in healthy young males, resistance exercise training induced increases in muscle mass and strength are absent. Whilst systemic hormone levels are carefully maintained in youth (unless illness or deficiency is present), levels of these hormones decrease with age, particularly in those that are not regularly physically active, indeed approximately 25-30% of older men have levels of testosterone which are below the threshold used to define hypogonadism. Therefore, there is significant need to understand the underlying mechanisms behind hormonally induced muscle mass regulation. Furthermore, in older age there is a resistance to traditional anabolic stimuli such as nutrition or resistance exercise, with older adults showing a blunted-anabolic hormonal profile in response to resistance training compared to young. These impairments to hormonal regulation with ageing may in part be responsible for the slow decline in muscle mass with age known as sarcopenia. Whilst all muscle-wasting conditions are of considerable concern, it is the loss of muscle in older age that poses the greatest socio-economic burden. Therefore there is a significant clinical need to identify contributing factors to this muscle loss so that they can be specifically targeted for intervention (i.e., pharmacological hormonal therapies).

The aims of this project are two fold: 1) Firstly we aim to investigate the impact of systemic hormone levels on control of muscle mass in healthy young adults undertaking a resistance exercise training program, we hypothesize that reduction of hormone levels in systemically normal young adults will impair MPS and muscle mass gains in response to resistance exercise training. 2) Secondly we aim to investigate the impact of enhancing testosterone levels in older adults on responsiveness to resistance exercise training and the contribution of systemic testosterone levels to muscle mass regulation in ageing, we hypothesize that increasing testosterone levels in older males will improve responsiveness to anabolic stimuli (RE-T).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: To achieve our aims we will recruit 16 young healthy males (Age: 18-30 y; BMI: 18-30kg/m2) and 16 older healthy males (Age: 65-75 y; BMI: 18-30kg/m2). Volunteers will then be randomly assigned to a testing group; 1) Young placebo trained (N=10), 2) Young gonadotropin releasing hormone analogue trained (3.6mg Zoladex subcutaneous injection (every 4 weeks) N=10), 3) Old placebo trained (N=10) and 4) Old Testosterone trained (Sustanon 250: 250 mg every 2-3wks intramuscular injection, N=10). All participants will receive whole body resistance exercise training for six weeks.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Regulation of Skeletal Muscle Protein Synthesis by Systemic Hormones and Its Influence on Ageing and Anabolic Resistance
Actual Study Start Date : December 15, 2016
Actual Primary Completion Date : November 15, 2018
Estimated Study Completion Date : February 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
Experimental: Old Testosterone trained

8 old participants (65-75 years old) who will receive resistance exercise training and Testosterone (Sustanon 250: 250 mg every 2wks)

Drug name: Sustanon 250 Generic Name: Testosterone Proprietary Name: N/A Formulation: 250mg of Testosterone in 1ml volume Dose: 250mg of testosterone Frequency: every 2 weeks Route: intramuscular injection

Drug: Sustanon 250
The frequency of the injection will be every 2 weeks, 250mg of testosterone, intramuscular injection.
Other Name: Testosterone

Placebo Comparator: Old Placebo trained
8 old participants (65-75 years old) who will receive resistance exercise training and Placebo every two weeks.
Other: Placebo
Other Name: Saline

Experimental: Young Zoladex trained

8 young participants (18-30 years old) who will receive resistance exercise training and Testosterone inhibitor (3.6mg Zoladex subcutaneous injection, one time over the study)

Drug name: Zoladex Generic Name: Gonadotropin-releasing hormone analogue; Goserelin Proprietary Name: N/A Formulation: Solution for injection Dose: 3.6mg Frequency: Single injection one time over the study. Route: Subcutaneous injection (abdomen) performed by clinician.

Drug: Zoladex
The frequency of the injection will be just one injection, 3.6 mg of Zoladex, Subcutaneous injection (abdomen).
Other Name: Gonadotropin-releasing hormone analogue; Goserelin

Placebo Comparator: Young placebo trained
8 young participants (18-30 years old) who will receive resistance exercise training and placebo, one time over the study.
Other: Placebo
Other Name: Saline




Primary Outcome Measures :
  1. Muscle Protein Synthesis [ Time Frame: 0-6 Weeks ]
    Comparison of muscle protein synthesis between young and older individuals when their testosterone levels decrease and increase, respectively; in response to 6 weeks whole body resistance exercise training



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   All participants are male.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Young (18-30y) and old (60-75y) males who are generally healthy

Exclusion Criteria:

  • Participation in a formal exercise regime
  • BMI < 18 or > 30 kg·m2
  • Active cardiovascular disease:

    • uncontrolled hypertension (BP > 160/100),
    • angina,
    • heart failure (class III/IV),
    • arrhythmia,
    • right to left cardiac shunt,
    • recent cardiac event
  • Taking beta-adrenergic blocking agents, statins, non-steroidal anti-inflammatory drugs or HRT
  • Cerebrovascular disease:

    • previous stroke,
    • aneurysm (large vessel or intracranial)
    • epilepsy
  • Respiratory disease including:

    • pulmonary hypertension,
    • COPD,
    • asthma,
  • Metabolic disease:

    • hyper and hypo parathyroidism,
    • Hypo and hyper gonadism
    • untreated hyper and hypothyroidism,
    • Cushing's disease,
    • type 1 or 2 diabetes
  • Active inflammatory bowel or renal disease
  • Malignancy
  • Altered hormonal profile
  • Recent steroid treatment (within 6 months) or hormone replacement therapy
  • Clotting dysfunction
  • Musculoskeletal or neurological disorders
  • Family history of early (<55y) death from cardiovascular disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03054168


Locations
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United Kingdom
Royal Derby Hospital Medical School
Derby, Derbyshire, United Kingdom, DE22 3DT
Sponsors and Collaborators
University of Nottingham
Investigators
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Principal Investigator: Philip J Atherton, Professor The University of Nottingham
Study Chair: Nathaniel Szewczyk, Ass. Proff The University of Nottingham
Publications:

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Responsible Party: Philip Atherton, University of Nottingham
ClinicalTrials.gov Identifier: NCT03054168    
Other Study ID Numbers: Hormones
First Posted: February 15, 2017    Key Record Dates
Last Update Posted: February 26, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Philip Atherton, University of Nottingham:
Protein Synthesis
Hypertrophy
Testosterone
Additional relevant MeSH terms:
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Sarcopenia
Muscular Atrophy
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Goserelin
Testosterone
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Androgens
Antineoplastic Agents, Hormonal
Antineoplastic Agents