UMIN-CTR Clinical Trial

Public title

Analysis of myokine dynamics due to relaxation of the oblique abdominal muscles -Randomised crossover trial-

Acronym

Analysis of myokine dynamics due to relaxation of the oblique abdominal muscles

Scientific Title

Analysis of myokine dynamics due to relaxation of the oblique abdominal muscles

Scientific Title:Acronym

Analysis of myokine dynamics due to relaxation of the oblique abdominal muscles

Region

Japan

Condition

healthy volunteers

Classification by specialty

Psychosomatic Internal Medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Investigating the dynamics of myokines due to skeletal muscle relaxation

Basic objectives2

Bio-availability

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Serum myokine concentrations for 15 items

Key secondary outcomes

1) Ultrasound elastography assessment of lateral abdominal wall tissue stiffness
Tissue stiffness of the subcutaneous fat, fascia, external oblique muscle, and internal oblique muscle is assessed by ultrasound elastography at the anterior, midaxillary, and posterior axillary lines before, immediately after, and 15 min after the intervention.

2) Serum myoglobin concentrations
Serum myoglobin concentrations are assessed before the intervention, immediately after the intervention, and 5, 10, and 15 min after the intervention. Serum myoglobin was added as a secondary outcome in protocol version 1.2 dated 17 April 2025.

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Single blind -participants are blinded

Control

Dose comparison

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

4.9 N-first sequence: In period 1, a 10-min focal manual loading procedure at 4.9 N is applied to the bilateral lateral abdominal wall during slow guided lateral trunk movement. After a 7-day interval, participants receive a 10-min movement-matched 0.49 N control procedure in period 2. Participant position, anatomical region, practitioner contact, trunk movement, contact sequence, and duration are matched between procedures; the planned difference is the target fingertip force.

Interventions/Control_2

0.49 N-first sequence: In period 1, participants receive a 10-min movement-matched 0.49 N control procedure applied to the bilateral lateral abdominal wall during slow guided lateral trunk movement. After a 7-day interval, participants receive a 10-min focal manual loading procedure at 4.9 N in period 2. Participant position, anatomical region, practitioner contact, trunk movement, contact sequence, and duration are matched between procedures; the planned difference is the target fingertip force.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

39

years-old

>=

Gender

Male

Key inclusion criteria

1 Men aged 20 to 39 at the time of obtaining consent
2 Individuals with a body mass index (BMI) ranging from 18.5 to 25

Key exclusion criteria

1 Individuals receiving treatment for an underlying medical condition.
2 Individuals deemed inappropriate for the research by the supervising physician due to the significant mental and physical load of participation.
3 Individuals deemed unfit by the study's supervisor

Target sample size

20

Name of lead principal investigator

1st name	Haruka
Middle name
Last name	Amitani

Organization

Kagoshima University Graduate School of Medical and Dental Sciences

Division name

Department of Psychosomatic Internal Medicine

Zip code

890-8520

Address

8-35-1 Sakuragaoka Kagoshima, Japan

TEL

0992755751

Email

amitani@m3.kufm.kagoshima-u.ac.jp

Name of contact person

1st name	Haruka
Middle name
Last name	Amitani

Organization

Kagoshima University Graduate School of Medical and Dental Sciences

Division name

Department of Psychosomatic Internal Medicine

Zip code

890-8520

Address

8-35-1 Sakuragaoka Kagoshima, Japan

TEL

0992755751

Homepage URL

Email

amitani@m3.kufm.kagoshima-u.ac.jp

Institute

Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences

Institute

Department

Personal name

Organization

Japan Health Organization

Organization

Division

Category of Funding Organization

Non profit foundation

Nationality of Funding Organization

Co-sponsor

Japan Health Organization

Name of secondary funder(s)

FUJIFILM Healthcare Corporation (in-kind support through the loan of an ARIETTA 750 DeepInsight ultrasound system)

Organization

Kagoshima University Hospital

Address

Sakuragaoka 8-35-1, Kagoshima

Tel

099-275-5934

Email

crmc@m2.kufm.kagoshima-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2024

Year

11

Month

15

Day

URL releasing protocol

The study protocol is not currently publicly available.

Publication of results

Unpublished

URL related to results and publications

No results are currently publicly available outside UMIN-CTR.

Number of participants that the trial has enrolled

20

Results

Twenty healthy men were randomised and all completed both procedures. The primary panel of 15 candidate myokine-related proteins was limited by assay censoring and variable interpretability, and no confirmatory treatment-specific effect was established. As a secondary outcome, lateral abdominal wall SWS reduction was greater after 4.9 N than 0.49 N, especially at the external oblique and deep intermuscular interface. No acute myoglobin increase or procedure-related adverse event was observed.

Results date posted

2026

Year

07

Month

30

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The participants were 20 healthy men, including 10 assigned to the 4.9 N-first sequence and 10 assigned to the 0.49 N-first sequence. Values before the first study period are presented as medians (interquartile ranges) for the overall population, 4.9 N-first sequence, and 0.49 N-first sequence, respectively: age, 28 (26-32), 26 (25-30), and 28 (27-33) years; height, 170.4 (166.4-173.0), 171.3 (168.2-173.7), and 168.4 (165.1-172.1) cm; weight, 62.8 (60.5-66.1), 64.9 (61.0-67.2), and 61.7 (56.7-64.4) kg; BMI, 21.80 (20.82-23.00), 21.90 (21.02-23.75), and 21.80 (19.97-21.90) kg/m2; fasting plasma glucose, 84.5 (77.5-90.2), 82.0 (76.5-84.8), and 90.0 (83.0-91.8) mg/dL; and fasting insulin, 3.50 (3.18-5.30), 3.25 (3.12-4.40), and 4.10 (3.50-5.50) uU/mL. No between-sequence hypothesis tests were performed for baseline characteristics.

Participant flow

Twenty healthy men were enrolled and randomised, with 10 assigned to the 4.9 N-first sequence and 10 assigned to the 0.49 N-first sequence. Participants in the 4.9 N-first sequence received the 4.9 N procedure in period 1 and the 0.49 N control procedure in period 2, whereas participants in the reverse sequence received the procedures in the opposite order. All 20 participants completed both study periods separated by 7 days. There were no discontinuations, withdrawals, or losses to follow-up. All 20 participants were included in the main elastography and serum myoglobin analyses. Analysis-specific sample sizes for the exploratory biomarker analyses varied because of assay censoring and complete-pair requirements.

Adverse events

No adverse events considered related to either the 4.9 N procedure or the 0.49 N control procedure were observed.

Outcome measures

[Primary outcomes: 15 candidate myokine-related proteins]

Each protein was measured at six time points during both study sessions: before the procedure, 5 min after the start of the procedure, immediately after completion, and 5, 10, and 15 min thereafter. A total of 240 measurements was planned for each protein. The numbers of quantifiable measurements/240 were: apelin 115, BDNF 202, erythropoietin 178, FABP3 240, FGF21 240, fractalkine 138, FSTL-1 225, IL-15 136, IL-6 160, irisin 186, LIF 141, myostatin/GDF-8 123, oncostatin M 220, musclin 230, and SPARC/osteonectin 240.

The extent of assay censoring differed among proteins. IL-6, IL-15, and myostatin/GDF-8 were remeasured using single-analyte ELISAs under protocol version 1.3. Because of the assay limitations and the post hoc selection of analytes for remeasurement, no confirmatory treatment-specific effect was established for the complete 15-protein panel.

The median treatment-specific BDNF responses (4.9 N minus 0.49 N) [bootstrap 95% CI] were 829 pg/mL [-33 to 1811] immediately after the procedure, 1521 pg/mL [-699 to 3585] at 5 min, 625 pg/mL [-251 to 2795] at 10 min, and 789 pg/mL [-520 to 3831] at 15 min. The time-normalised Delta AUC0-15 min was 771 pg/mL [-623 to 3363]. The Holm-adjusted P value was 0.539 for each of the five BDNF endpoints (analysis-specific n = 12-14).

Median treatment-specific ELISA changes (4.9 N minus 0.49 N) [bootstrap 95% CI] were:

| Protein | Immediately post | Post +5 min | Post +10 min | Post +15 min |
|---|---|---|---|---|
| IL-6, pg/mL | 0.36 [0.03 to 1.77] | 0.09 [-0.45 to 0.76] | 0.21 [-1.08 to 1.44] | 0.05 [-0.67 to 0.59] |
| IL-15, pg/mL | 0.00 [-0.28 to 3.87] | 1.20 [0.00 to 6.67] | 2.84 [0.41 to 7.95] | 0.70 [-0.56 to 4.44] |
| Myostatin/GDF-8, pg/mL | 33.8 [9.5 to 56.1] | 6.7 [-16.3 to 38.5] | 4.9 [-17.1 to 21.2] | 18.4 [-0.4 to 34.6] |

None of the 12 ELISA analyte-by-time-point comparisons met the nominal threshold after Holm adjustment. For myostatin/GDF-8 immediately after the procedure, the raw P value was 0.0043 and the Holm-adjusted P value was 0.0515. All other Holm-adjusted P values were at least 0.653. The biomarker analyses were interpreted as exploratory.


[Secondary outcome 1: lateral abdominal wall shear wave speed]

Within-session SWS reduction was defined as pre-procedure SWS minus post-procedure SWS. The treatment-specific difference was defined as the reduction after the 4.9 N procedure minus the corresponding reduction after the 0.49 N control procedure. Positive values indicate a greater SWS reduction after the 4.9 N procedure. Values are medians (IQRs) or medians [bootstrap 95% CIs] (n = 20).

| Layer and time point | SWS reduction after 4.9 N, m/s | SWS reduction after 0.49 N, m/s | Treatment-specific difference, m/s [95% CI] | Holm-adjusted P |
|---|---|---|---|---|
| Subcutaneous fat, immediately post | 0.098 (0.034 to 0.376) | -0.003 (-0.192 to 0.065) | 0.215 [0.002 to 0.334] | 0.0434 |
| Subcutaneous fat, post +15 min | 0.149 (0.088 to 0.421) | -0.020 (-0.235 to 0.082) | 0.296 [0.159 to 0.463] | 0.0104 |
| Fascia 1, immediately post | 0.302 (0.122 to 0.597) | -0.069 (-0.284 to 0.435) | 0.325 [0.115 to 0.443] | 0.0434 |
| Fascia 1, post +15 min | 0.321 (0.085 to 0.640) | 0.106 (-0.152 to 0.242) | 0.323 [0.011 to 0.515] | 0.0458 |
| External oblique, immediately post | 0.390 (0.287 to 0.807) | 0.092 (-0.071 to 0.275) | 0.326 [0.133 to 0.707] | 0.0304 |
| External oblique, post +15 min | 0.386 (0.242 to 0.635) | -0.091 (-0.172 to 0.149) | 0.501 [0.266 to 0.617] | 0.0044 |
| Fascia 2, immediately post | 0.772 (0.461 to 1.234) | 0.080 (-0.125 to 0.333) | 0.610 [0.302 to 0.928] | 0.0051 |
| Fascia 2, post +15 min | 1.041 (0.573 to 1.211) | 0.096 (-0.119 to 0.274) | 0.780 [0.482 to 1.160] | 0.0096 |

Fascia 2 was operationally defined as the deep echogenic interface between the external and internal oblique muscles. Site-specific and internal oblique analyses were exploratory. A sequence-dependent shift in the period-2 pre-procedure Fascia 2 value was observed, and complete washout could not be confirmed. First-period-only and sequence-stratified analyses produced directionally consistent but less precise Fascia 2 estimates.


[Secondary outcome 2: serum myoglobin]

The within-participant difference in change from baseline was calculated as the change after the 4.9 N procedure minus the corresponding change after the 0.49 N control procedure (n = 20). Median treatment-specific changes [bootstrap 95% CI] were 3.2 ng/mL [-2.9 to 5.8] immediately after the procedure, -1.7 ng/mL [-6.2 to 5.6] at 5 min, -1.6 ng/mL [-8.0 to 8.8] at 10 min, and -0.1 ng/mL [-4.3 to 3.8] at 15 min. The Holm-adjusted P value was 1.000 at each time point.

The treatment-specific Delta AUC0-15 min was -11.4 ng min/mL [-80.2 to 96.4], and the peak-change difference was 1.4 ng/mL [-5.8 to 6.7]; the Holm-adjusted P value was 1.000 for both comparisons. No acute treatment-specific myoglobin increase was detected within the 15-min observation period. This result does not constitute a comprehensive safety assessment or exclude delayed changes.


[Other secondary measures]

Fasting plasma glucose, fasting insulin, height, body weight, and body-composition measurements were evaluated descriptively as participant characteristics. No hypothesis test of a treatment-specific effect was performed for these measures.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2024

Year

09

Month

17

Day

Date of IRB

2024

Year

09

Month

17

Day

Anticipated trial start date

2024

Year

11

Month

06

Day

Last follow-up date

2024

Year

12

Month

26

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2024

Year

11

Month

15

Day

Last modified on

2026

Year

08

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000064172