Trial Outcomes & Findings for Mechanisms Underlying Local and Systemic Effects of Massage (NCT NCT04131712)

Last Updated: 2024-05-21

Results Overview

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

Recruitment status

COMPLETED

Study phase

Target enrollment

44 participants

Primary outcome timeframe

9 days

Results posted on

2024-05-21

Participant Flow

Subjects were actively recruited from the University of Kentucky campus as well as from the surrounding Lexington community through local advertisement using IRB approved recruitment flyers or newspaper advertisement. Recruitment occurred between August of 2020 and May 2023. The COVID pandemic shut down research activities at the University of Kentucky for some time impacting recruitment. Thus, the PI decided to focus on randomization of immobilized groups

Consent, inclusion/exclusion criteria checklist, participant characteristics such as height and weight, and pregnancy testing were conducted prior to randomization.

Participant milestones

Participant milestones
Measure	Ambulatory Control 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.	Immobilization Control 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 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. Massage: 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.
Overall Study STARTED	9	19	16
Overall Study COMPLETED	9	16	16
Overall Study NOT COMPLETED	0	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ambulatory Control 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 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. Massage: 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.	Immobilization Control 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 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. Massage: 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.
Overall Study COVID related	0	0	2	0
Overall Study PI withdrawal, subject could not follow study schedule	0	0	1	0

Baseline Characteristics

Mechanisms Underlying Local and Systemic Effects of Massage

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ambulatory Control n=9 Participants 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 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. Massage: 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.	Immobilization Control n=16 Participants 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 n=16 Participants 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. Massage: 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.	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	—	16 Participants n=5 Participants	16 Participants n=4 Participants	41 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	22.83 years STANDARD_DEVIATION 3.31 • n=5 Participants	—	22.64 years STANDARD_DEVIATION 3.93 • n=5 Participants	22.07 years STANDARD_DEVIATION 3.77 • n=4 Participants	22.46 years STANDARD_DEVIATION 3.66 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	—	12 Participants n=5 Participants	12 Participants n=4 Participants	28 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	—	4 Participants n=5 Participants	4 Participants n=4 Participants	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	—	1 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	—	15 Participants n=5 Participants	13 Participants n=4 Participants	36 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	—	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	—	15 Participants n=5 Participants	14 Participants n=4 Participants	37 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	—	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	9 participants n=5 Participants	—	16 participants n=5 Participants	16 participants n=4 Participants	41 participants n=21 Participants

PRIMARY outcome

Timeframe: 9 days

Population: Only one biopsy post 9 days was taken in the ambulatory groups only and thus % change could not be calculated. For the immobilization control group, one biopsy specimen could not be accurately analyzed due to tissue quality.

Outcome measures

Outcome measures
Measure	Ambulatory Control 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 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. Massage: 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.	Immobilization Control n=15 Participants 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 n=16 Participants 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. Massage: 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.
Percent Change in Myofiber Cross Sectional Area (CSA).	—	—	-15.1 percent change from baseline Standard Deviation 5.1	-13.4 percent change from baseline Standard Deviation 3.0

PRIMARY outcome

Timeframe: 9 days

Population: Participants were not randomized to the ambulatory massage group. For the immobilization control group, one biopsy specimen could not be accurately analyzed due to tissue quality.

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.

Outcome measures

Outcome measures
Measure	Ambulatory Control n=8 Participants 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 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. Massage: 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.	Immobilization Control n=15 Participants 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 n=16 Participants 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. Massage: 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.
Myofibrillar Protein Synthesis Rate (MyoKsyn).	1.19 percentage of protein produced per day Standard Deviation 0.25	—	1.04 percentage of protein produced per day Standard Deviation 0.31	1.07 percentage of protein produced per day Standard Deviation 0.29

SECONDARY outcome

Timeframe: 9 days

Population: Data was not generated.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 9 days

Population: Data was not generated.

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.

Outcome measures

Outcome data not reported

Adverse Events

Ambulatory Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Ambulatory Massage

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Immobilization Control

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Immobilization Massage

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ambulatory Control n=9 participants at risk 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 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. Massage: 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.	Immobilization Control n=16 participants at risk 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 n=16 participants at risk 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. Massage: 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.
Nervous system disorders Nausea	0.00% 0/9 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	— 0/0 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	0.00% 0/16 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	12.5% 2/16 • Number of events 2 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.
Musculoskeletal and connective tissue disorders Pain	0.00% 0/9 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	— 0/0 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	6.2% 1/16 • Number of events 1 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	6.2% 1/16 • Number of events 1 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.
Skin and subcutaneous tissue disorders Blister	0.00% 0/9 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	— 0/0 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	12.5% 2/16 • Number of events 2 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	6.2% 1/16 • Number of events 1 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.
General disorders Fatigue	0.00% 0/9 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	— 0/0 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	6.2% 1/16 • Number of events 1 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.	6.2% 1/16 • Number of events 1 • Adverse events were monitored over the 9 day study period and for approximately 3 days post last biopsy. AEs and SAEs were collected according to the standard definitions used by clinicaltrials.gov.

Additional Information

Douglas Long

University of Kentucky

Phone: 859-323-5438

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place