Back to resultsSex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse (MAC)
Primary Purpose
Atrophy of Muscle Due to Disuse, Rehabilitation
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Resistance Exercise Rehabilitation
Walking-based rehabilitation
Sponsored by
About this trial
This is an interventional other trial for Atrophy of Muscle Due to Disuse
Eligibility Criteria
Inclusion Criteria:
- All races and ethnic backgrounds
- Men and women, age 50-65 years
- Generally healthy (see exclusion criteria)
- Able and willing to provide informed consent
- Ability to speak and read English
Exclusion Criteria:
- Compromised musculoskeletal function that precludes safe participation or use of crutches
- Pre-menopausal women
- Hypogonadal men (testosterone <300 ng/dL)
- Women taking hormone replacement therapy (HRT)
- Sarcopenia (European Working Group on Sarcopenia in Older People, EWGSOP102)
- Clinically significant heart disease (e.g. New York Heart Classification greater than grade II; ischemia)
- Peripheral vascular disease
- History of claudication
- Pulmonary disease
- History of systemic or pulmonary embolus
- Uncontrolled blood pressure (systolic BP>170, diastolic BP>95 mmHg)
- Impaired renal function (creatinine >1.5 mg/dl)
- Anemia (hematocrit <33)
- Untreated thyroid disease (abnormal TSH)
- A recent history (<12 months) of GI bleed
- Diabetes mellitus or other untreated endocrine or metabolic disease
- Electrolyte abnormalities
- Any history of stroke, hypo- or hyper-coagulation disorders
- Employment requiring long (>1 h) uninterrupted period of standing
- Inability to meet study travel requirements (e.g. manual geared car)
- Recent history of balance issues or falls.
- Recent (3 years) treated cancer other than basal cell carcinoma
- Systemic steroids, anabolic steroids, growth hormone or immunosuppressant use within 12 months
- Recent (6 months) adherence to a weight-loss or weight-gain diet
- Weight change of 5% or more in previous 6 months
- Body mass index >30 or excess body fat that compromises muscle biopsy collection
- Body mass index <20 or recent history (<12 month) of disordered eating
- Acute infectious disease or chronic infection
- Alcohol or drug abuse
- Any other condition or event considered exclusionary by study physician
Sites / Locations
- University of Texas Medical BranchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Male Rehabilitation (M-REHAB)
Male Control (M-CON)
Female Rehabilitation (F-REHAB)
Female Control (F-CON)
Arm Description
Disuse + resistance exercise rehabilitation
Disuse + ambulatory control rehabilitation
Disuse + resistance exercise rehabilitation
Disuse + ambulatory control rehabilitation
Outcomes
Primary Outcome Measures
Quantitative RNA-sequencing
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Quantitative RNA-sequencing
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Muscle function
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Muscle function
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Muscle function
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Muscle function
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Muscle function
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Body (leg) composition
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Body (leg) composition
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Body (leg) composition
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Body (leg) composition
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Body (leg) composition
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Secondary Outcome Measures
Muscle fiber cross sectional area
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Muscle fiber cross sectional area
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Muscle fiber cross sectional area
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Muscle fiber cross sectional area
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Muscle fiber cross sectional area
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Muscle fiber type
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Muscle fiber type
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Muscle fiber type
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Muscle fiber type
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Muscle fiber type
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Diet recall
A multi-pass 24-hour dietary recall using the Automated Self Assessment 24-h dietary assessment tool to determine habitual food intake
Diet recall
A multi-pass 24-hour dietary recall using the Automated Self Assessment 24-h dietary assessment tool to determine habitual food intake
Physical activity
Accelerometers will placed on the waist and ankle to measure physical activity
Physical activity
Accelerometers will placed on the waist and ankle to measure physical activity
Physical activity
Accelerometers will placed on the waist and ankle to measure physical activity
Full Information
NCT ID
NCT04151901
First Posted
October 9, 2019
Last Updated
April 4, 2023
Sponsor
The University of Texas Medical Branch, Galveston
1. Study Identification
Unique Protocol Identification Number
NCT04151901
Brief Title
Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
Acronym
MAC
Official Title
Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 27, 2021 (Actual)
Primary Completion Date
October 31, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Medical Branch, Galveston
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrophy of Muscle Due to Disuse, Rehabilitation
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
Participant
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Male Rehabilitation (M-REHAB)
Arm Type
Experimental
Arm Description
Disuse + resistance exercise rehabilitation
Arm Title
Male Control (M-CON)
Arm Type
Experimental
Arm Description
Disuse + ambulatory control rehabilitation
Arm Title
Female Rehabilitation (F-REHAB)
Arm Type
Experimental
Arm Description
Disuse + resistance exercise rehabilitation
Arm Title
Female Control (F-CON)
Arm Type
Experimental
Arm Description
Disuse + ambulatory control rehabilitation
Intervention Type
Other
Intervention Name(s)
Resistance Exercise Rehabilitation
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Walking-based rehabilitation
Intervention Description
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 Measure Information:
Title
Quantitative RNA-sequencing
Description
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Time Frame
Study day 1 (before starting leg disuse)
Title
Quantitative RNA-sequencing
Description
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Time Frame
Study day 7 (after finishing leg disuse)
Title
Quantitative RNA-sequencing
Description
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Time Frame
Study day 7 (after 1 bout of rehabilitation)
Title
Quantitative RNA-sequencing
Description
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Time Frame
Study day 9 (after 2 bouts of rehabilitation)
Title
Quantitative RNA-sequencing
Description
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Time Frame
Study Day 11 (after 3 bouts of rehabilitation)
Title
Quantitative RNA-sequencing
Description
RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome
Time Frame
Study Day 21 (after finishing 7 bouts of rehabilitation)
Title
Muscle function
Description
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Time Frame
Study day 1 (before starting leg disuse)
Title
Muscle function
Description
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Time Frame
Study day 7 (after 1 bout of rehabilitation)
Title
Muscle function
Description
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Time Frame
Study day 9 (after 2 bouts of rehabilitation)
Title
Muscle function
Description
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Time Frame
Study Day 11 (after 3 bouts of rehabilitation)
Title
Muscle function
Description
Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque)
Time Frame
Study Day 21 (after finishing 7 bouts of rehabilitation)
Title
Body (leg) composition
Description
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Time Frame
Study day 1 (before starting leg disuse)
Title
Body (leg) composition
Description
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Time Frame
Study day 7 (after finishing leg disuse)
Title
Body (leg) composition
Description
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Time Frame
Study day 9 (after 2 bouts of rehabilitation)
Title
Body (leg) composition
Description
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Time Frame
Study Day 11 (after 3 bouts of rehabilitation)
Title
Body (leg) composition
Description
Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry
Time Frame
Study Day 21 (after finishing 7 bouts of rehabilitation)
Secondary Outcome Measure Information:
Title
Muscle fiber cross sectional area
Description
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Time Frame
Study day 1 (before starting leg disuse)
Title
Muscle fiber cross sectional area
Description
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Time Frame
Study day 7 (after finishing leg disuse)
Title
Muscle fiber cross sectional area
Description
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Time Frame
Study day 9 (after 2 bouts of rehabilitation)
Title
Muscle fiber cross sectional area
Description
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Time Frame
Study Day 11 (after 3 bouts of rehabilitation)
Title
Muscle fiber cross sectional area
Description
Muscle biopsy samples will be evaluated for muscle fiber cross sectional area
Time Frame
Study Day 21 (after finishing 7 bouts of rehabilitation)
Title
Muscle fiber type
Description
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Time Frame
Study day 1 (before starting leg disuse)
Title
Muscle fiber type
Description
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Time Frame
Study day 7 (after finishing leg disuse)
Title
Muscle fiber type
Description
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Time Frame
Study day 9 (after 2 bouts of rehabilitation)
Title
Muscle fiber type
Description
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Time Frame
Study Day 11 (after 3 bouts of rehabilitation)
Title
Muscle fiber type
Description
Muscle biopsy samples will be evaluated for muscle fiber type distribution
Time Frame
Study Day 21 (after finishing 7 bouts of rehabilitation)
Title
Diet recall
Description
A multi-pass 24-hour dietary recall using the Automated Self Assessment 24-h dietary assessment tool to determine habitual food intake
Time Frame
Familiarization session (~1 week before starting leg disuse)
Title
Diet recall
Description
A multi-pass 24-hour dietary recall using the Automated Self Assessment 24-h dietary assessment tool to determine habitual food intake
Time Frame
Study day 11 (after two bouts of rehabilitation)
Title
Physical activity
Description
Accelerometers will placed on the waist and ankle to measure physical activity
Time Frame
Study Days -7 to Day 0 (1 week prior to starting leg disuse)
Title
Physical activity
Description
Accelerometers will placed on the waist and ankle to measure physical activity
Time Frame
Study Days 1-6 (1 week of disuse)
Title
Physical activity
Description
Accelerometers will placed on the waist and ankle to measure physical activity
Time Frame
Study Days 7-21 (2 weeks of rehabilitation)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
All races and ethnic backgrounds
Men and women, age 50-65 years
Generally healthy (see exclusion criteria)
Able and willing to provide informed consent
Ability to speak and read English
Exclusion Criteria:
Compromised musculoskeletal function that precludes safe participation or use of crutches
Pre-menopausal women
Hypogonadal men (testosterone <300 ng/dL)
Women taking hormone replacement therapy (HRT)
Sarcopenia (European Working Group on Sarcopenia in Older People, EWGSOP102)
Clinically significant heart disease (e.g. New York Heart Classification greater than grade II; ischemia)
Peripheral vascular disease
History of claudication
Pulmonary disease
History of systemic or pulmonary embolus
Uncontrolled blood pressure (systolic BP>170, diastolic BP>95 mmHg)
Impaired renal function (creatinine >1.5 mg/dl)
Anemia (hematocrit <33)
Untreated thyroid disease (abnormal TSH)
A recent history (<12 months) of GI bleed
Diabetes mellitus or other untreated endocrine or metabolic disease
Electrolyte abnormalities
Any history of stroke, hypo- or hyper-coagulation disorders
Employment requiring long (>1 h) uninterrupted period of standing
Inability to meet study travel requirements (e.g. manual geared car)
Recent history of balance issues or falls.
Recent (3 years) treated cancer other than basal cell carcinoma
Systemic steroids, anabolic steroids, growth hormone or immunosuppressant use within 12 months
Recent (6 months) adherence to a weight-loss or weight-gain diet
Weight change of 5% or more in previous 6 months
Body mass index >30 or excess body fat that compromises muscle biopsy collection
Body mass index <20 or recent history (<12 month) of disordered eating
Acute infectious disease or chronic infection
Alcohol or drug abuse
Any other condition or event considered exclusionary by study physician
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emily Lantz, PhD
Phone
281-886-3018
Email
ejlantz@utmb.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Blake Rasmussen, PhD
Email
blrasmus@utmb.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Blake Rasmussen, PhD
Organizational Affiliation
University of Texas
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Medical Branch
City
Galveston
State/Province
Texas
ZIP/Postal Code
77555
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Lantz, PhD
Email
ejlantz@utmb.edu
First Name & Middle Initial & Last Name & Degree
Blake Rasmussen, PhD
12. IPD Sharing Statement
Learn more about this trial
Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse
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