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Trial record 2 of 4 for:    paddon-jones

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

Tracking Information
First Submitted Date  ICMJE October 9, 2019
First Posted Date  ICMJE November 5, 2019
Last Update Posted Date April 9, 2020
Estimated Study Start Date  ICMJE June 2020
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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
  • 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
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2019)
  • 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
  • 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
  • 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
  • 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
  • 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
  • Muscle fiber type [ Time Frame: Study day 1 (before starting leg disuse) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution
  • Muscle fiber type [ Time Frame: Study day 7 (after finishing leg disuse) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution
  • Muscle fiber type [ Time Frame: Study day 9 (after 2 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution
  • Muscle fiber type [ Time Frame: Study Day 11 (after 3 bouts of rehabilitation) ]
    Muscle biopsy samples will be evaluated for muscle fiber type distribution
  • 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
  • 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
  • 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
  • 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
  • Physical activity [ Time Frame: Study Days 1-6 (1 week of disuse) ]
    Accelerometers will placed on the waist and ankle to measure physical activity
  • Physical activity [ Time Frame: Study Days 7-21 (2 weeks of rehabilitation) ]
    Accelerometers will placed on the waist and ankle to measure physical activity
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
Official Title  ICMJE Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single (Participant)
Primary Purpose: Other
Condition  ICMJE
  • Atrophy of Muscle Due to Disuse
  • Rehabilitation
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: Male Rehabilitation (M-REHAB)
    Disuse + resistance exercise rehabilitation
    Intervention: Other: Resistance Exercise Rehabilitation
  • Experimental: Male Control (M-CON)
    Disuse + ambulatory control rehabilitation
    Intervention: Other: Walking-based rehabilitation
  • Experimental: Female Rehabilitation (F-REHAB)
    Disuse + resistance exercise rehabilitation
    Intervention: Other: Resistance Exercise Rehabilitation
  • Experimental: Female Control (F-CON)
    Disuse + ambulatory control rehabilitation
    Intervention: Other: Walking-based rehabilitation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 1, 2019)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date May 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Emily Lantz, PhD 281-886-3018 ejlantz@utmb.edu
Contact: Doug Paddon-Jones, PhD djpaddon@utmb.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04151901
Other Study ID Numbers  ICMJE 19-0045
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The University of Texas Medical Branch, Galveston
Study Sponsor  ICMJE The University of Texas Medical Branch, Galveston
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Doug Paddon-Jones, PhD University of Texas
PRS Account The University of Texas Medical Branch, Galveston
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP