Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse (MAC)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04151901
Recruitment Status : Not yet recruiting
First Posted : November 5, 2019
Last Update Posted : April 9, 2020
Sponsor:
Information provided by (Responsible Party):
The University of Texas Medical Branch, Galveston

Brief Summary:

This project is a 2-phase, randomized clinical trial that includes 7 days of unilateral leg disuse (Phase 1), immediately followed by 14 days of bilateral leg rehabilitation (Phase 2). The investigators will recruit cohorts of healthy middle-aged men and women to address their aims:

  • Demonstrate the sex-specific effects of skeletal muscle disuse (Phase 1)
  • Identify key molecular determinates of susceptibility of skeletal muscle atrophy (Phase 1)
  • Map the early, sex-specific molecular time-course of rehabilitation (Phase 2)
  • Determine if disused and healthy muscle respond similarly to exercise (Phase 2)

Healthy, middle-age men and post-menopausal women (50-65 years) will be recruited from the greater Houston/Galveston area. This under-represented research demographic demonstrate few negative metabolic or phenotypic signs of advanced age, but are at increased risk of being hospitalized and experiencing accelerated loss of lean mass and muscle function that parallels a much older population.

The goal of this study is to characterize phenotypic and molecular skeletal muscle changes in middle-aged men and women during critical periods of disuse and rehabilitation and ultimately direct the development of targeted and effective prevention and treatment strategies.


Condition or disease Intervention/treatment Phase
Atrophy of Muscle Due to Disuse Rehabilitation Other: Resistance Exercise Rehabilitation Other: Walking-based rehabilitation Not Applicable

Detailed Description:

The negative health consequences of muscular disuse in aging populations are unequivocal. While descriptive, outcome data on disuse and recovery are abundant, key knowledge gaps limit researcher's ability to implement evidence-based, rehabilitation strategies. Limiters include: i) an inability to identify individuals most susceptible to disuse, ii) insufficient information to differentiate between, and respond to, disuse atrophy in men and women, iii) limited insight into the mechanisms driving adaptation to early rehabilitative exercise, and iv) the assumption that disused and healthy skeletal muscle will have a similar, positive response to resistance exercise. The investigators will complete a 2-phase, randomized clinical trial at the University of Texas Medical Branch (UTMB). The protocol includes 7-days of unilateral leg disuse (ULD; Phase 1), immediately followed by 14-days of bilateral leg rehabilitation (Phase 2). Healthy, middle-aged men (n=40) and (post-menopausal) women (n=40), (50-65 y) will be recruited; a neglected research demographic who present with a largely youthful phenotype, but are at risk of accelerated disuse atrophy.

This project will provide a highly powered, detailed phenotypic characterization of the continuum of adults most and least susceptible to muscular disuse. Clinical outcomes will be supported by RNA deep sequencing and pathway analysis to establish a platform that: i) improves scientists' ability to identify higher-risk individuals and ii) provides insight into time-sensitive, sex-specific and effective rehabilitation strategies. Findings and reposed molecular data from this study, may help identify future therapeutic targets and serve as an uncomplicated/comorbidity-free baseline for clinical trials in populations experiencing disuse atrophy.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single (Participant)
Primary Purpose: Other
Official Title: Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : August 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rehabilitation

Arm Intervention/treatment
Experimental: Male Rehabilitation (M-REHAB)
Disuse + resistance exercise rehabilitation
Other: Resistance Exercise Rehabilitation
Following disuse, the REHAB groups (M-REHAB, F-REHAB) will complete monitored resistance exercise rehabilitation sessions using an isokinetic dynamometer at a similar relative load at each rehab visit.

Experimental: Male Control (M-CON)
Disuse + ambulatory control rehabilitation
Other: Walking-based rehabilitation
Following disuse, the CON groups (M-CON, F-CON) will complete 30 minutes of monitored walking at a moderate intensity at each rehab visit.

Experimental: Female Rehabilitation (F-REHAB)
Disuse + resistance exercise rehabilitation
Other: Resistance Exercise Rehabilitation
Following disuse, the REHAB groups (M-REHAB, F-REHAB) will complete monitored resistance exercise rehabilitation sessions using an isokinetic dynamometer at a similar relative load at each rehab visit.

Experimental: Female Control (F-CON)
Disuse + ambulatory control rehabilitation
Other: Walking-based rehabilitation
Following disuse, the CON groups (M-CON, F-CON) will complete 30 minutes of monitored walking at a moderate intensity at each rehab visit.




Primary Outcome Measures :
  1. Quantitative RNA-sequencing [ Time Frame: Study day 1 (before starting leg disuse) ]
    RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  2. Quantitative RNA-sequencing [ Time Frame: Study day 7 (after finishing leg disuse) ]
    RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  3. Quantitative RNA-sequencing [ Time Frame: Study day 7 (after 1 bout of rehabilitation) ]
    RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  4. Quantitative RNA-sequencing [ Time Frame: Study day 9 (after 2 bouts of rehabilitation) ]
    RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  5. Quantitative RNA-sequencing [ Time Frame: Study Day 11 (after 3 bouts of rehabilitation) ]
    RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  6. Quantitative RNA-sequencing [ Time Frame: Study Day 21 (after finishing 7 bouts of rehabilitation) ]
    RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome

  7. Muscle function [ Time Frame: Study day 1 (before starting leg disuse) ]
    Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  8. Muscle function [ Time Frame: Study day 7 (after 1 bout of rehabilitation) ]
    Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  9. Muscle function [ Time Frame: Study day 9 (after 2 bouts of rehabilitation) ]
    Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  10. Muscle function [ Time Frame: Study Day 11 (after 3 bouts of rehabilitation) ]
    Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  11. Muscle function [ Time Frame: Study Day 21 (after finishing 7 bouts of rehabilitation) ]
    Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)

  12. Body (leg) composition [ Time Frame: Study day 1 (before starting leg disuse) ]
    Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  13. Body (leg) composition [ Time Frame: Study day 7 (after finishing leg disuse) ]
    Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  14. Body (leg) composition [ Time Frame: Study day 9 (after 2 bouts of rehabilitation) ]
    Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  15. Body (leg) composition [ Time Frame: Study Day 11 (after 3 bouts of rehabilitation) ]
    Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry

  16. Body (leg) composition [ Time Frame: Study Day 21 (after finishing 7 bouts of rehabilitation) ]
    Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry


Secondary Outcome Measures :
  1. Muscle fiber cross sectional area [ Time Frame: Study day 1 (before starting leg disuse) ]
    Muscle biopsy samples will be evaluated for muscle fiber cross sectional area

  2. Muscle fiber cross sectional area [ Time Frame: Study day 7 (after finishing leg disuse) ]
    Muscle biopsy samples will be evaluated for muscle fiber cross sectional area

  3. Muscle fiber cross sectional area [ Time Frame: Study day 9 (after 2 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber cross sectional area

  4. Muscle fiber cross sectional area [ Time Frame: Study Day 11 (after 3 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber cross sectional area

  5. Muscle fiber cross sectional area [ Time Frame: Study Day 21 (after finishing 7 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber cross sectional area

  6. Muscle fiber type [ Time Frame: Study day 1 (before starting leg disuse) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution

  7. Muscle fiber type [ Time Frame: Study day 7 (after finishing leg disuse) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution

  8. Muscle fiber type [ Time Frame: Study day 9 (after 2 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution

  9. Muscle fiber type [ Time Frame: Study Day 11 (after 3 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution

  10. Muscle fiber type [ Time Frame: Study Day 21 (after finishing 7 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution

  11. Diet recall [ Time Frame: Familiarization session (~1 week before starting leg disuse) ]
    A multi-pass 24-hour dietary recall using the Automated Self Assessment 24-h dietary assessment tool to determine habitual food intake

  12. Diet recall [ Time Frame: Study day 11 (after two bouts of rehabilitation) ]
    A multi-pass 24-hour dietary recall using the Automated Self Assessment 24-h dietary assessment tool to determine habitual food intake

  13. Physical activity [ Time Frame: Study Days -7 to Day 0 (1 week prior to starting leg disuse) ]
    Accelerometers will placed on the waist and ankle to measure physical activity

  14. Physical activity [ Time Frame: Study Days 1-6 (1 week of disuse) ]
    Accelerometers will placed on the waist and ankle to measure physical activity

  15. Physical activity [ Time Frame: Study Days 7-21 (2 weeks of rehabilitation) ]
    Accelerometers will placed on the waist and ankle to measure physical activity



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. All races and ethnic backgrounds
  2. Men and women, age 50-65 years
  3. Generally healthy (see exclusion criteria)
  4. Able and willing to provide informed consent
  5. Ability to speak and read English

Exclusion Criteria:

  1. Compromised musculoskeletal function that precludes safe participation or use of crutches
  2. Pre-menopausal women
  3. Hypogonadal men (testosterone <300 ng/dL)
  4. Women taking hormone replacement therapy (HRT)
  5. Sarcopenia (European Working Group on Sarcopenia in Older People, EWGSOP102)
  6. Clinically significant heart disease (e.g. New York Heart Classification greater than grade II; ischemia)
  7. Peripheral vascular disease
  8. History of claudication
  9. Pulmonary disease
  10. History of systemic or pulmonary embolus
  11. Uncontrolled blood pressure (systolic BP>170, diastolic BP>95 mmHg)
  12. Impaired renal function (creatinine >1.5 mg/dl)
  13. Anemia (hematocrit <33)
  14. Untreated thyroid disease (abnormal TSH)
  15. A recent history (<12 months) of GI bleed
  16. Diabetes mellitus or other untreated endocrine or metabolic disease
  17. Electrolyte abnormalities
  18. Any history of stroke, hypo- or hyper-coagulation disorders
  19. Employment requiring long (>1 h) uninterrupted period of standing
  20. Inability to meet study travel requirements (e.g. manual geared car)
  21. Recent history of balance issues or falls.
  22. Recent (3 years) treated cancer other than basal cell carcinoma
  23. Systemic steroids, anabolic steroids, growth hormone or immunosuppressant use within 12 months
  24. Recent (6 months) adherence to a weight-loss or weight-gain diet
  25. Weight change of 5% or more in previous 6 months
  26. Body mass index >30 or excess body fat that compromises muscle biopsy collection
  27. Body mass index <20 or recent history (<12 month) of disordered eating
  28. Acute infectious disease or chronic infection
  29. Alcohol or drug abuse
  30. Any other condition or event considered exclusionary by study physician

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): NCT04151901


Contacts
Layout table for location contacts
Contact: Emily Lantz, PhD 281-886-3018 ejlantz@utmb.edu
Contact: Doug Paddon-Jones, PhD djpaddon@utmb.edu

Sponsors and Collaborators
The University of Texas Medical Branch, Galveston
Investigators
Layout table for investigator information
Principal Investigator: Doug Paddon-Jones, PhD University of Texas
Layout table for additonal information
Responsible Party: The University of Texas Medical Branch, Galveston
ClinicalTrials.gov Identifier: NCT04151901    
Other Study ID Numbers: 19-0045
First Posted: November 5, 2019    Key Record Dates
Last Update Posted: April 9, 2020
Last Verified: September 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Atrophy
Pathological Conditions, Anatomical