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 :
Recruiting
First Posted : November 5, 2019
Last Update Posted : April 4, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
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 : | 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 |
Actual Study Start Date : | August 27, 2021 |
Estimated Primary Completion Date : | October 31, 2023 |
Estimated Study Completion Date : | November 30, 2023 |

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. |
- 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
- 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

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.
Ages Eligible for Study: | 50 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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

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
Contact: Emily Lantz, PhD | 281-886-3018 | ejlantz@utmb.edu | |
Contact: Blake Rasmussen, PhD | blrasmus@utmb.edu |
United States, Texas | |
University of Texas Medical Branch | Recruiting |
Galveston, Texas, United States, 77555 | |
Contact: Emily Lantz, PhD ejlantz@utmb.edu | |
Principal Investigator: Blake Rasmussen, PhD |
Principal Investigator: | Blake Rasmussen, PhD | University of Texas |
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 4, 2022 |
Last Verified: | March 2022 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Atrophy Pathological Conditions, Anatomical |