UMIN-CTR Clinical Trial

Public title

Genome-wide serum microRNA profiling before and after sleeve gastrectomy: a pilot study comparing metabolically healthy and metabolically unhealthy obesity

Acronym

SG-miRNA Obesity Phenotype Study

Scientific Title

Genome-wide serum microRNA profiling before and after sleeve gastrectomy: a pilot study comparing metabolically healthy and metabolically unhealthy obesity

Scientific Title:Acronym

SG-miRNA Obesity Phenotype Pilot Study

Region

Japan

Condition

Severe obesity

Classification by specialty

Endocrinology and Metabolism

Surgery in general

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

To comprehensively analyse serum microRNA expression profiles before and after sleeve gastrectomy in patients with severe obesity, and to identify phenotype-specific miRNA expression patterns and candidate biomarkers predictive of post-operative metabolic improvement in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO).

Basic objectives2

Others

Basic objectives -Others

Exploratory

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Primary outcomes

Changes in serum microRNA expression profiles before and 3 months after sleeve gastrectomy, assessed by genome-wide Agilent SurePrint G3 Human miRNA microarray (8x60K)

Key secondary outcomes

Changes in HOMA-IR, fasting glucose, fasting insulin, HbA1c, CRP, BMI, and percentage total weight loss before and 3 months after sleeve gastrectomy

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

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

18

years-old

<=

Age-upper limit

65

years-old

>=

Gender

Male and Female

Key inclusion criteria

Patients diagnosed with morbid obesity at our institution between 08/2020and 03/2021
Patients aged 18 years or older
Availability of relevant clinical information from medical records
Informed consent (or opt-out) obtained from patients or their legal representatives

Key exclusion criteria

Cases with poor sample quality unsuitable for analysis
Cases with insufficient clinical information
Cases who declined participation (opted out)
(Relevant comorbidities, e.g., concurrent malignancies, etc.)

Target sample size

8

Name of lead principal investigator

1st name	Susumu
Middle name
Last name	Inamine

Organization

Ohama Daiichi Hospital

Division name

Center for Metabolic and Bariatric Surgery

Zip code

900-0005

Address

Ameku1000, Naha city, Okinawa, Japan

TEL

0570-00-5171

Email

inamine@me.com

Name of contact person

1st name	Susumu
Middle name
Last name	Inamine

Organization

Ohama Daiichi Hospital

Division name

Center for Metabolic and Bariatric Surgery

Zip code

900-0005

Address

Ameu1000, Naha city, Okinawa, Japan

TEL

0570-00-5171

Homepage URL

Email

i.ssm@mac.com

Institute

Ohama Daiichi Hospital

Institute

Department

Personal name

Organization

Ohama Daiichi Hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ohama Daiichi Hospital

Address

Ameku1000, Naha city, Okinawa, Japan

Tel

0570-00-5171

Email

i.ssm@mac.com

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

2026

Year

05

Month

13

Day

URL releasing protocol

N/A

Publication of results

Partially published

URL related to results and publications

N/A

Number of participants that the trial has enrolled

8

Results

Genome-wide serum microRNA profiling before and 3 months after sleeve gastrectomy (SG) in 8 patients (MHO n=4, MUO n=4; JASSO criteria). MUO had higher HbA1c, HOMA-IR, fasting glucose/insulin, and AST (all p=0.029). Pre-op miR-5100 predicted post-op HOMA-IR reduction (rho=-0.878, p=0.004). Pre-op miR-5585-3p predicted CRP reduction (rho=-0.854, p=0.007). Set analysis identified 10 microRNAs detected in all MUO but none in MHO. miR-8069 decreased in 7/8 after SG (Wilcoxon p=0.016).

Results date posted

2026

Year

05

Month

13

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Eight patients with severe obesity (BMI >=35 kg/m2) were classified into
metabolically healthy obesity (MHO, n=4) and metabolically unhealthy
obesity (MUO, n=4) groups per JASSO criteria.

[MHO group / MUO group (mean +/- SD)]
- Sex (female/male): 3/1 / 2/2
- Age (years): 47.5 +/- 2.7 / 45.8 +/- 12.2 (p=0.772)
- BMI (kg/m2): 61.3 +/- 11.7 / 56.2 +/- 14.0 (p=0.886)
- Visceral fat area (cm2): 354 +/- 65 / 391 +/- 144 (p=0.686)

[Glucose metabolism]
- HbA1c (%): 5.6 +/- 0.1 / 7.5 +/- 0.7 (p=0.029)
- Fasting glucose (mg/dL): 98 +/- 14 / 130 +/- 8 (p=0.029)
- Fasting insulin (uU/mL): 18.9 +/- 4.1 / 40.7 +/- 6.4 (p=0.029)
- HOMA-IR: 4.6 +/- 1.3 / 13.1 +/- 2.4 (p=0.029)

[Lipids and blood pressure]
- Triglycerides (mg/dL): 113 +/- 22 / 114 +/- 42 (p=0.772)
- HDL-C (mg/dL): 51 +/- 16 / 43 +/- 4 (p=1.000)
- Systolic BP (mmHg): 150 +/- 23 / 139 +/- 15 (p=0.686)

[Inflammation and liver]
- CRP (mg/dL): 0.9 +/- 0.3 / 3.3 +/- 2.2 (p=0.114)
- AST (U/L): 18 +/- 3 / 32 +/- 4 (p=0.029)

Statistical test: Mann-Whitney U test.
BMI and visceral fat area were comparable between groups, while MUO had
significantly higher glucose metabolism indices (HbA1c, fasting glucose,
fasting insulin, HOMA-IR) and AST.

Participant flow

Patients with severe obesity scheduled for sleeve gastrectomy (SG) at the
Center for Metabolic and Bariatric Surgery, Ohama Daiichi Hospital, were
consecutively screened, and eight eligible patients were enrolled.

- Enrolled: 8 patients (MHO n=4, MUO n=4)
- Pre-operative serum samples collected: 8 (100%)
- Sleeve gastrectomy performed: 8 (100%)
- Post-operative (3 months) serum samples collected: 8 (100%)
- Included in analysis: 8 (no dropouts)

All participants completed pre- and post-operative sample collection and
analysis with no dropouts. Mean percentage total weight loss (%TWL) at
3 months: MHO group 18.2 +/- 3.4%, MUO group 22.8 +/- 7.2% (p=0.343).

Adverse events

This is an observational study with no study-specific intervention.
Sleeve gastrectomy was performed as standard clinical care. No
study-related adverse events occurred. There were no serious adverse
events associated with pre-operative or post-operative (3-month) blood
sampling.

Outcome measures

[Primary outcome measures]
1. Spearman rank correlation coefficients between pre-operative serum
microRNA expression (log2-transformed) and baseline metabolic
parameters as well as their changes (Delta) at 3 months post-SG:
- HOMA-IR, fasting glucose, fasting insulin, HbA1c
- CRP, AST
- Triglycerides, HDL-C
- BMI, visceral fat area, systolic blood pressure
- Percentage total weight loss (%TWL) at 3 months

[Secondary outcome measures]
2. Differences in pre-operative microRNA profiles between MHO and MUO
groups, evaluated by qualitative set analysis based on dichotomous
detection patterns (Detected vs. Not Detected).

3. Within-group comparison of microRNA expression between pre- and
post-operative (3 months) time points, using Welchs t-test with
false discovery rate (FDR) correction at p < 0.05.

4. Whole-cohort comparison of microRNA expression between pre- and
post-operative (3 months) time points, using Wilcoxon signed-rank
test.

[Measurement methods]
Serum microRNA expression was measured using the Agilent SurePrint G3
Human miRNA microarray (8x60K, 2,549 probes), and log2-transformed
signal values after quantile normalisation were used for analysis.
Statistical analyses were performed using Python 3.12 / SciPy 1.11.
Statistical significance was defined as p < 0.05.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2020

Year

04

Month

10

Day

Date of IRB

2020

Year

07

Month

07

Day

Anticipated trial start date

2020

Year

08

Month

18

Day

Last follow-up date

2021

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This is a single-center, prospective observational cohort study (pilot study).

[Factors examined (Exposures)]
1) Metabolic phenotype: metabolically healthy obesity (MHO) vs.
metabolically unhealthy obesity (MUO) classified per JASSO criteria,
using CT-measured visceral fat area (>=100 cm2) and a metabolic
component score (fasting glucose, triglycerides, HDL-cholesterol,
and blood pressure; one point each). Scores 0-1 = MHO; 2-3 = MUO.
2) Sleeve gastrectomy (SG)
3) Pre-operative serum microRNA expression measured by Agilent
SurePrint G3 Human miRNA microarray (8x60K, 2,549 probes,
quantile normalisation)

[Outcomes]
Primary: Association between pre-operative serum microRNA expression
levels and changes in metabolic parameters (HOMA-IR, CRP, fasting
glucose, fasting insulin) at 3 months post-SG.
Secondary: (1) Differences in microRNA profiles between MHO and MUO
phenotypes; (2) Pre- to post-operative changes in microRNA expression
across all participants.

[Study design]
Single-center, prospective observational cohort study.

[Sampling]
Non-probability consecutive sampling of eight patients with severe
obesity (BMI >=35 kg/m2) undergoing sleeve gastrectomy at the Center
for Metabolic and Bariatric Surgery, Ohama Daiichi Hospital
(MHO n=4, MUO n=4). Four complementary statistical approaches were
applied: Spearman correlation, Wilcoxon signed-rank test, qualitative
set analysis, and Welchs t-test with false discovery rate correction.

Registered date

2026

Year

05

Month

13

Day

Last modified on

2026

Year

05

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000070425