Systemic Hormones and Muscle Protein Synthesis

February 22, 2019 updated by: Philip Atherton, University of Nottingham

The Regulation of Skeletal Muscle Protein Synthesis by Systemic Hormones and Its Influence on Ageing and Anabolic Resistance

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Derbyshire
      • Derby, Derbyshire, United Kingdom, DE22 3DT
        • Royal Derby Hospital Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
0-6 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nottingham

Investigators

  • Principal Investigator: Philip J Atherton, Professor, The University of Nottingham
  • Study Chair: Nathaniel Szewczyk, Ass. Proff, The University of Nottingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2016

Primary Completion (Actual)

November 15, 2018

Study Completion (Anticipated)

February 15, 2019

Study Registration Dates

First Submitted

February 10, 2017

First Submitted That Met QC Criteria

February 10, 2017

First Posted (Actual)

February 15, 2017

Study Record Updates

Last Update Posted (Actual)

February 26, 2019

Last Update Submitted That Met QC Criteria

February 22, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Hormones

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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