Muscle AtrophyNCT04131712
Mechanisms Underlying Local and Systemic Effects of Massage
A study testing Massage in people with Muscle Atrophy, run by Esther Dupont-Versteegden at 1 site in United States.
Trial summary
The purpose of this study is to determine whether massage can attenuate the loss of muscle mass in humans after a short period of disuse. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Muscle Atrophy
- What is being tested?
- Massage
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2020to 1 Jun 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women 18-30 years of age.
- All races and ethnic backgrounds.
- Non-smoker and generally healthy.
Who cannot join
- Have a current lower extremity musculoskeletal injury or compromised musculoskeletal function that would not allow the safe use of crutches or a brace.
- Previous lower extremity surgeries or injury.
- Activities of daily living require long periods of standing or driving a manual transmission car.
- Body mass index (BMI) under 27.
- Evidence or signs and symptoms of metabolic syndrome or disorder (diagnosis of diabetes or insulin resistance, elevated BP, high fasting blood sugar, abnormal cholesterol or triglyceride levels).
- Thyroid disorder.
Show all 12Show fewer
- Acute or chronic infections.
- Use of systemic steroids, anabolic steroids, or growth hormone.
- Chronic aspirin or NSAID use (unless it can be safely stopped prior to the biopsies), and any other use of an anticoagulant (e.g., Coumadin) or history of bleeding including history of hypo- or hyper-coagulation disorders.
- Lidocaine allergy (1% lidocaine is the local anesthetic used during the muscle biopsy procedure).
- Any other condition or events considered exclusionary by the PI and/or physician, such as non-compliance.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether massage can attenuate the loss of muscle mass in humans after a short period of disuse.
Read the detailed description
The loss of skeletal muscle mass is a common symptom associated with diseases such as cancer, AIDS, diabetes, and congestive heart failure, and with aging. Muscle atrophy is associated with poor disease prognosis and decreased quality of life and therefore, maintaining muscle size and reducing the loss of muscle during disuse atrophy is of vital significance. Mechanical stimulation of muscle, such as during resistance exercise, stimulates protein synthesis that increases muscle protein content, and muscle size. The investigators have shown that mechanical stimulation applied to skeletal muscle in the form of massage is an effective mechanotherapy in rats, since it leads to a shift in protein turnover favoring anabolism, attenuation of muscle loss and enhanced regrowth after disuse-induced atrophy. Whether the same positive effect of massage occurs in humans is currently unknown, but would be extremely beneficial for skeletal muscle and overall health in case where resistance exercise is contraindicated or not feasible. In addition to the direct anabolic effects on the massaged rat muscle, the investigators have shown an equally beneficial response on the homologous muscle in the contralateral non-massaged limb. This novel finding indicated the existence of indirect mechanisms that could have profound systemic effects beyond the massaged muscle. Extracellular vesicles (EVs) are lipid membrane-bound vesicles released from cells with the ability to modulate function of cells from which they are released, as well as in cells with which they fuse. As such EVs are likely mediators of the well-documented but poorly-understood effects of massage in humans on the brain and other organs, such as relief of pain, anxiety or depression or changes in immunity. Therefore, the goal of this proposal is to determine anabolic effects of massage in human muscle, and to identify whether EVs released with massage are candidates for beneficial effects of this mechanotherapy on muscle as well as other organs. In Aim 1 the investigators will address the following hypothesis: Massage acts as a mechanotherapy by attenuating muscle atrophy through a shift in protein biogenesis towards anabolism in humans. Using a novel massage device we will apply mechanical load to muscle undergoing atrophy through unilateral lower limb suspension and muscle size as well as protein synthesis and degradation will be determined. In Aim 2 the investigators will test the hypothesis that massage attenuates the loss of EVs during atrophy by enhancing EV biogenesis in muscle. The investigators will measure EVs and their miRNA cargo in the serum, and markers of EV biogenesis in muscle of human subjects from Aim 1. Results from this study will indicate not only whether mechanotherapy, such as massage, can attenuate atrophy and enhance anabolic processes during disuse, but also determine whether EVs are a candidate mechanism for the overall health benefits of massage.
- Conditions
- Muscle Atrophy
- Being tested
- Massage
- Keywords
- Massage, Muscle, Extracellular Vesicles, Atrophy
- Medical subject headings
- Muscular Atrophy, Atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MassageOther
A custom-made cyclic compressive loading (CCL) device will be used to apply a mechanical load to the left thigh of the participants. Massage application using a 35 Newton load will be applied for 15 minutes every other day over the course of 7 days for a total of four massages.
| Study group | Role | What they receive |
|---|---|---|
| Ambulatory Control | No intervention | Following baseline assessments, participants will be randomized into the ambulatory group for the remainder of the study. Atrophy will not be induced and massage intervention will not be applied. Ambulatory groups will be recruited following the immobilized groups. |
| Ambulatory Massage | Sham comparator | Following baseline assessments, participants will be randomized into the ambulatory group for the remainder of the study. No atrophy induction. Four massage treatments will be applied every other day until the end of the study. Ambulatory groups will be recruited following the immobilized groups. Receives: Other: Massage |
| Immobilization Control | No intervention | Following baseline assessments, participants will be randomized into the unilateral lower limb suspension group undergoing atrophy for the remainder of the study. Massage intervention will not be applied. |
| Immobilization Massage | Experimental | Following baseline assessments, participants will be randomized into the unilateral lower limb suspension group undergoing atrophy for the remainder of the study. Four massage treatments will be applied every other day until the end of the study. Receives: Other: Massage |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Myofiber Cross Sectional Area (CSA).
The ability of massage to attenuate the atrophic response to disuse will be determined. Muscle biopsies of the vastus lateralis will be used to quantify myofiber cross-sectional area. The percent change in myofiber size between day 7 and day -2 was used.
Calculation details: [(day 7 CSA) - (day -2 CSA)/(day -2 CSA)]*100
Measured: 9 days
Myofibrillar Protein Synthesis Rate (MyoKsyn).
The ability of massage to attenuate the atrophic response to disuse due to protein synthesis will be determined. Muscle biopsies of the vastus lateralis will be used to quantify protein synthesis rates.
Measured: 9 days
Secondary outcomes (2)
Percent Change in Serum Extracellular Vesicle Number (EV #).
The ability of massage to attenuate the loss in EV number will be determined. Serum will be used to quantify EV numbers. The percent change in EVs between day 7 and day -2 was used.
Measured: 9 days
Percent Change in the Expression of Muscle Rab27b mRNA.
The ability of massage to attenuate the loss in Rab27b protein expression will be determined. Muscle biopsies of the vastus lateralis will be used to quantify muscle Rab27b expression. The percent change in muscle Rab27b expression between day 7 and day -2 was used.
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2019
- Study start1 Aug 2020
- Primary completion1 Jun 2023
- Study completion1 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Muscle AtrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Esther Dupont-Versteegden
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oklahoma, National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Sponsor-investigator, Esther Dupont-Versteegden, University of Kentucky
- Investigators
- Esther Dupont-Versteegden, Ph.D., Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04131712
- Sponsor's protocol ID
- 43499
- Other IDs
- R21AT010847
- Status last verified
- May 2024
- First submitted
- 16 Oct 2019
- Last updated
- 21 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms Underlying Local and Systemic Effects of Massage
- ClinicalTrials.gov ID
- NCT04131712
- Acronym / sponsor ID
- 43499
- Conditions
- Muscle Atrophy
- Keywords
- Massage, Muscle, Extracellular Vesicles, Atrophy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Esther Dupont-VersteegdenUniversity, hospital or other
- Collaborators
- University of Oklahoma, National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 18 Oct 2019 (actual)
- Results
- Posted 21 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether massage can attenuate the loss of muscle mass in humans after a short period of disuse.
Detailed description
The loss of skeletal muscle mass is a common symptom associated with diseases such as cancer, AIDS, diabetes, and congestive heart failure, and with aging. Muscle atrophy is associated with poor disease prognosis and decreased quality of life and therefore, maintaining muscle size and reducing the loss of muscle during disuse atrophy is of vital significance. Mechanical stimulation of muscle, such as during resistance exercise, stimulates protein synthesis that increases muscle protein content, and muscle size. The investigators have shown that mechanical stimulation applied to skeletal muscle in the form of massage is an effective mechanotherapy in rats, since it leads to a shift in protein turnover favoring anabolism, attenuation of muscle loss and enhanced regrowth after disuse-induced atrophy. Whether the same positive effect of massage occurs in humans is currently unknown, but would be extremely beneficial for skeletal muscle and overall health in case where resistance exercise is contraindicated or not feasible. In addition to the direct anabolic effects on the massaged rat muscle, the investigators have shown an equally beneficial response on the homologous muscle in the contralateral non-massaged limb. This novel finding indicated the existence of indirect mechanisms that could have profound systemic effects beyond the massaged muscle. Extracellular vesicles (EVs) are lipid membrane-bound vesicles released from cells with the ability to modulate function of cells from which they are released, as well as in cells with which they fuse. As such EVs are likely mediators of the well-documented but poorly-understood effects of massage in humans on the brain and other organs, such as relief of pain, anxiety or depression or changes in immunity. Therefore, the goal of this proposal is to determine anabolic effects of massage in human muscle, and to identify whether EVs released with massage are candidates for beneficial effects of this mechanotherapy on muscle as well as other organs. In Aim 1 the investigators will address the following hypothesis: Massage acts as a mechanotherapy by attenuating muscle atrophy through a shift in protein biogenesis towards anabolism in humans. Using a novel massage device we will apply mechanical load to muscle undergoing atrophy through unilateral lower limb suspension and muscle size as well as protein synthesis and degradation will be determined. In Aim 2 the investigators will test the hypothesis that massage attenuates the loss of EVs during atrophy by enhancing EV biogenesis in muscle. The investigators will measure EVs and their miRNA cargo in the serum, and markers of EV biogenesis in muscle of human subjects from Aim 1. Results from this study will indicate not only whether mechanotherapy, such as massage, can attenuate atrophy and enhance anabolic processes during disuse, but also determine whether EVs are a candidate mechanism for the overall health benefits of massage.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Ambulatory Control | No intervention | –Following baseline assessments, participants will be randomized into the ambulatory group for the remainder of the study. Atrophy will not be induced and massage intervention will not be applied. Ambulatory groups will be recruited following the immobilized groups. |
| Ambulatory Massage | Sham comparator | Other: MassageFollowing baseline assessments, participants will be randomized into the ambulatory group for the remainder of the study. No atrophy induction. Four massage treatments will be applied every other day until the end of the study. Ambulatory groups will be recruited following the immobilized groups. |
| Immobilization Control | No intervention | –Following baseline assessments, participants will be randomized into the unilateral lower limb suspension group undergoing atrophy for the remainder of the study. Massage intervention will not be applied. |
| Immobilization Massage | Experimental | Other: MassageFollowing baseline assessments, participants will be randomized into the unilateral lower limb suspension group undergoing atrophy for the remainder of the study. Four massage treatments will be applied every other day until the end of the study. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Men and women 18-30 years of age.
- All races and ethnic backgrounds.
- Non-smoker and generally healthy.
Key exclusion criteria (12 listed)
- Have a current lower extremity musculoskeletal injury or compromised musculoskeletal function that would not allow the safe use of crutches or a brace.
- Previous lower extremity surgeries or injury.
- Activities of daily living require long periods of standing or driving a manual transmission car.
- Body mass index (BMI) under 27.
- Evidence or signs and symptoms of metabolic syndrome or disorder (diagnosis of diabetes or insulin resistance, elevated BP, high fasting blood sugar, abnormal cholesterol or triglyceride levels).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MassageA custom-made cyclic compressive loading (CCL) device will be used to apply a mechanical load to the left thigh of the participants. Massage application using a 35 Newton load will be applied for 15 minutes every other day over the course of 7 days for a total of four massages. | Other | Ambulatory Massage, Immobilization Massage |
Primary outcome
Percent Change in Myofiber Cross Sectional Area (CSA).
Time frame: 9 days
The ability of massage to attenuate the atrophic response to disuse will be determined. Muscle biopsies of the vastus lateralis will be used to quantify myofiber cross-sectional area. The percent change in myofiber size between day 7 and day -2 was used. Calculation details: [(day 7 CSA) - (day -2 CSA)/(day -2 CSA)]*100
Myofibrillar Protein Synthesis Rate (MyoKsyn).
Time frame: 9 days
The ability of massage to attenuate the atrophic response to disuse due to protein synthesis will be determined. Muscle biopsies of the vastus lateralis will be used to quantify protein synthesis rates.
2 secondary outcomes
Percent Change in Serum Extracellular Vesicle Number (EV #).
Time frame: 9 days
Percent Change in the Expression of Muscle Rab27b mRNA.
Time frame: 9 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Esther Dupont-Versteegden, Ph.D. principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Massage in people with Muscle Atrophy, run by Esther Dupont-Versteegden at 1 site in United States.
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 12 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: finished, as of the sponsor's last update on 21 May 2024. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Change in Myofiber Cross Sectional Area (CSA). (time frame: 9 days). The study lists 2 primary outcomes in all. 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 21 May 2024.