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Muscle AtrophyEarly Phase 1NCT03069781

The Effects of 17β-estradiol on Skeletal Muscle

A Early Phase 1 study testing 17β-estradiol and Polycose in people with Muscle Atrophy, run by McMaster University at 1 site in Canada.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 30 years, men onlyHealthy volunteers can take part
Conditions the study is for
Muscle Atrophy
What is being tested?
17β-estradiol and Polycose
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteCanada
Study dates
May 2017to 14 Aug 2018
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 30 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Canada1 site
  • McMaster Univeristy

    Hamilton, Ontario

Other trials in Canada

About this study

Official title: The Effects of 17β-estradiol on Skeletal Muscle Mass Following Immobilization

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.

Read the detailed description

Design and detailed description of methodology This is a parallel-group randomized controlled trial, blinded to the 17β-estradiol (n=10) or placebo (n=10) supplement administered every day for 10 days. Twelve healthy young men (age: 18-25yrs; BMI: 22-33 kg/m2) will be recruited to participate in this study. During phone or e-mail conversations we will explain the purpose and experimental design of the study and address all questions the participants might have (see telephone and email scripts). Participants will visit the laboratory for a screening to assess whether they are eligible to participate in this study. During the screening we will first explain the experimental design and obtain written informed consent. A medical questionnaire will be completed by the participants to assess their general health and use of medication. Body height and mass will be measured as baseline characteristics of the participants. Participants will be requested to fill out a 3-d dietary record to assess habitual energy and protein intake. Participants will be randomly assigned to the 17β-estradiol (n=10) or placebo (n=10) supplementation group. Randomization will be performed using a computerized list randomizer (https://www.random.org/lists/), and participants will be sequentially allocated to a condition according to the randomized list. The experimental trial is composed of 10 days of 17β-estradiol (Estrace, Acerus Pharmaceuticals Corporation, Mississauga, ON, Canada or placebo (400 mg/day Polycose, Abbott Laboratories, St. Laurent, QC, Canada) supplementation, including 3 days of pre-immobilization, and 7 days of single leg immobilization. Three days prior to immobilization (t=-3 d) a blood sample will be obtained and muscle strength will be assessed before daily 17β-estradiol or placebo supplementation will be initiated. Participants will consume 1mg/day for 3-days and 3mg/day for 7-days of Estrace or 400 mg/day of Polycose for 7-days. The estrogen and placebo bottles are coded to ensure complete blinding to both researchers and participants. Additional blood samples will be obtained to assess the compliance of the participants to the supplementation. In addition, at t=-3 d a saliva sample will be obtained before ingesting 150 mL of deuterium-labeled water (D2O). Daily saliva sampling will be continued until the end of the experimental trial to assess precursor pool enrichments. Dietary intake will be controlled for 10-days (including 3 d prior to immobilization and 7 d of immobilization) providing an energy balanced diet containing 1 weight per day equally distributed over breakfast, lunch, and dinner (15). Participants will be instructed to refrain from vigorous-intensity physical activity (running, fast cycling, competitive sports, carrying heavy loads, etc.) and refrain from alcohol consumption for 3 d prior to and during the 7-day single leg immobilization. Daily activity will be monitored with a SenseWear Armband, which subjects will be required to wear from t=-3 d until the end of the experimental trial.

Participants will have one leg immobilized by means of knee bracing (http://www.breg.com/products/knee-bracing/post-op) thus the contralateral limb will act as an internal control. The leg to be immobilized will be chosen in a random counterbalanced manner to result in equal numbers of participants having their weaker or stronger legs being immobilized. The brace (http://www.breg.com/products/knee-bracing/post-op) will be worn in a fixed flexion position at 140° (i.e., 40° from full extension) with a plastic band that is removed to check for pressure points daily and resealed with a custom-modified plastic strap that is melted to seal the strap, as we have done previously19,20. The reason for this is that the brace cannot be removed without breaking the plastic seal, but could be broken in the case of an emergency and the brace removed entirely, if required. Using this model of disuse we have found the immobilizing brace to be well tolerated, not restrictive, and importantly it does not occlude for popliteal and/or femoral artery blood flow, and we have had no cases of edema or venous thrombosis in previous studies. Participants will also be provided with elastic support bandages to lessen the risk of deep vein thrombosis.

On t=0 d, a blood sample, saliva sample and muscle biopsy will be collected for the assessment of muscle protein synthesis rates. Muscle strength and volume will be assessed using a Biodex and ultrasonography respectively. A knee brace will be placed to start the 7-day single leg immobilization phase. The choice of leg for immobilization will be randomized and balanced for dominance according to maximal isometric strength. At the end of the immobilization phase (t=7 d), a blood sample will be obtained, muscle biopsies will be collected from both the immobilized and non-immobilized leg, and muscle volume and strength will be assessed. After strength is assessed in both legs, a further muscle biopsy will be taken to assess the effect of 17β-estradiol on muscle response to a single bout of exercise (Biodex) in both the non-immobilized and immobilized leg 3-hrs after the exercise bout.

Conditions
Muscle Atrophy
Being tested
17β-estradiol, Polycose
Keywords
estrogen
Medical subject headings
Muscular Atrophy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 17β-estradiolDrug

    Also called Estrance

    1mg/day for 3-days and 3mg/day for 7-days of Estrance

  • PolycoseDrug

    Also called Enteral Nutrition Formulas

    400 mg/day for 10-days of Polycose (Abbott Laboratories, St. Laurent, QC, Canada)

Study groups in NCT03069781
Study groupRoleWhat they receive
17β-estradiolExperimental1mg/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.
Receives: Drug: 17β-estradiol
PlaceboPlacebo comparator400 mg/day for 10-days of Polycose (Abbott Laboratories, St. Laurent, QC, Canada).7 Day Breg Knee Brace unilateral immobilization.
Receives: Drug: Polycose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Muscle protein synthesis and breakdown rates

    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.

    Measured: Prior to immobilization (-3-0 d) and over the 7 days of immobilization (0-7 d).

Secondary outcomes (2)
  1. Muscle size

    Ultrasound will be performed on both legs to assess leg muscle volume and mass.

    Measured: At t=0 and after 7 days of immobilization.

  2. Muscle strength

    Muscle strength will be assessed using Biodex.

    Measured: At t=0 and after 7 days of immobilization.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2017
  2. Study startMay 2017 (estimated)
  3. Primary completionMay 2018 (estimated)
  4. Study completion14 Aug 2018

Why it stopped: Lack of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel-group, double-blinded, randomized controlled trial.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03069781
Sponsor's protocol ID
REB-2919
Status last verified
Aug 2018
First submitted
27 Feb 2017
Last updated
16 Aug 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing 17β-estradiol and Polycose in people with Muscle Atrophy, run by McMaster University at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Muscle protein synthesis and breakdown rates (time frame: Prior to immobilization (-3-0 d) and over the 7 days of immobilization (0-7 d).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2018.

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