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The Effects of 17β-estradiol on Skeletal Muscle

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ClinicalTrials.gov Identifier: NCT03069781
Recruitment Status : Withdrawn (Lack of funding)
First Posted : March 3, 2017
Last Update Posted : August 16, 2018
Sponsor:
Information provided by (Responsible Party):
Stuart Phillips, McMaster University

Brief Summary:

The maintenance of skeletal muscle mass and function is critical for healthy aging. Muscle loss with disuse, termed muscle disuse muscle atrophy, leads to impaired functional capacity, the onset of insulin resistance, as well as a heightened risk for morbidity and mortality. With advancing age there is a chronic wasting of muscle. This is especially true in women, where rapid rates of decline in muscle mass and greater anabolic resistance are experienced around the time of menopause, despite higher protein synthesis rates. As women have a longer life expectancy, they are particularly venerable to age-related frailty and morbidity.

Skeletal muscle protein turnover serves to maintain the optimal function of proteins and also provides plasticity of the tissue during altered demands such as during increased loading or unloading of the muscle. Reduced periods of physical activity also have a similar, albeit milder, impact on skeletal muscle and most, people will likely experience multiple bouts of skeletal muscle disuse during their lifetime from which some, particularly older adult women, will fail to fully recover. Thus, muscle disuse atrophy is a significant and continuing problem as reclamation of lost muscle mass, strength/function, and potentially metabolic health (particularly insulin-induced glucose disposal), following disuse is oftentimes incomplete and may be further exacerbated after menopause.

Previous evidence has demonstrated that in the loss of muscle mass is less pronounced in post-menopausal women when receiving hormone replacement therapy. Skeletal muscle has estrogen-β-receptors on the cell membrane, in the cytoplasm and on the nuclear membrane, and therefore a direct mechanistic link between low estrogen levels and a decrease MPS. Interestingly, despite higher rates of protein synthesis, older women still lose muscle mass with advancing age. It has been suggested that the negative muscle protein balance is due to an enhanced rate of MPB. Insulin is a potent inhibitor of MPB and estrogen has been shown to enhance insulin sensitivity in skeletal muscle. However, to our knowledge, no study has examined the efficacy of estrogen supplementation to attenuate the losses of skeletal muscle mass and function during a period of disuse. The findings of this investigation may yield critical data for those who wish to combat skeletal muscle disuse atrophy, particularly after menopause.


Condition or disease Intervention/treatment Phase
Muscle Atrophy Drug: 17β-estradiol Drug: Polycose Early Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel-group, double-blinded, randomized controlled trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Both forms of supplementation (estrogen and placebo) will be packaged and administered in identical fashion.
Primary Purpose: Basic Science
Official Title: The Effects of 17β-estradiol on Skeletal Muscle Mass Following Immobilization
Estimated Study Start Date : May 2017
Estimated Primary Completion Date : May 2018
Actual Study Completion Date : August 14, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 17β-estradiol
1mg/day for 3-days and 3mg/day for 7-days of 17β-estradiol (Estrace, Acerus Pharmaceuticals Corporation, Mississauga, ON, Canada). 7 Day Breg Knee Brace unilateral immobilization.
Drug: 17β-estradiol
1mg/day for 3-days and 3mg/day for 7-days of Estrance
Other Name: Estrance

Placebo Comparator: Placebo
400 mg/day for 10-days of Polycose (Abbott Laboratories, St. Laurent, QC, Canada).7 Day Breg Knee Brace unilateral immobilization.
Drug: Polycose
400 mg/day for 10-days of Polycose (Abbott Laboratories, St. Laurent, QC, Canada)
Other Name: Enteral Nutrition Formulas




Primary Outcome Measures :
  1. Muscle protein synthesis and breakdown rates [ Time Frame: Prior to immobilization (-3-0 d) and over the 7 days of immobilization (0-7 d). ]
    Myofibrillar protein will be extracted from the muscle biopsies. Myofibrillar protein-bound 2H-alanine enrichments will be determined by gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) by Metabolic Solutions, Nashua, NH as described previously (16). The saliva and plasma samples will be analyzed for 2H enrichments by cavity ring-down spectroscopy by Metabolic Solutions. Fractional synthetic rates of muscle protein synthesis will be calculated by dividing the increment in muscle protein-bound enrichment between two muscle biopsies over time by the average enrichment in total body water/plasma.


Secondary Outcome Measures :
  1. Muscle size [ Time Frame: At t=0 and after 7 days of immobilization. ]
    Ultrasound will be performed on both legs to assess leg muscle volume and mass.

  2. Muscle strength [ Time Frame: At t=0 and after 7 days of immobilization. ]
    Muscle strength will be assessed using Biodex.



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Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Generally healthy, non-smoking as assessed by questionnaire
  2. Willing and able to provide informed consent
  3. BMI between 22 and 29 kg/m2

Exclusion Criteria:

  1. Any concurrent medical, orthopedic, or psychiatric condition that, in the opinion of the Investigators, would compromise the ability to comply with the study requirements
  2. Significant orthopedic, cardiovascular, pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine disorders or other disease that would preclude oral 17β-estradiol supplementation
  3. Current illnesses which could interfere with the study (e.g. prolonged severe diarrhea, regurgitation, difficulty swallowing)
  4. Excessive alcohol consumption (>21 units/week)
  5. History of bleeding diathesis, platelet or coagulation disorders, or antiplatelet/anticoagulation therapy
  6. Personal or family history of clotting disorder or deep vein thrombosis
  7. Concomitant use of corticosteroids, testosterone replacement therapy (ingestion, injection, or transdermal), or any anabolic steroid

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): NCT03069781


Locations
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Canada, Ontario
McMaster Univeristy
Hamilton, Ontario, Canada
Sponsors and Collaborators
McMaster University
Investigators
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Principal Investigator: Stuart Phillips, PhD McMaster University

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Responsible Party: Stuart Phillips, Professor, McMaster University
ClinicalTrials.gov Identifier: NCT03069781     History of Changes
Other Study ID Numbers: REB-2919
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Stuart Phillips, McMaster University:
estrogen
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Muscular Atrophy
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female