UMIN-ICDS Clinical Trial

Public title

Association of DNA methylation of inflammatory, anti-inflammatory, and longevity-related genes with complications and prognosis in patients with chronic kidney disease

Acronym

Association of DNA Methylation with Complications and Prognosis in Patients with Chronic Kidney Disease

Scientific Title

Association of epigenetic alterations in inflammatory/anti-inflammatory cytokine and longevity-related genes with complications and prognosis in patients with chronic kidney disease

Scientific Title:Acronym

Association of epigenetic alterations with complications and prognosis in patients with chronic kidney disease

Region

Japan

Condition

Chronic kidney disease

Classification by specialty

Nephrology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

While chronic kidney disease(CKD)patients frequently develop cardiovascular and nutritional complications, the underlying pathophysiology remains unclarified. Recently, epigenetic modifications-specifically DNA methylation-have been implicated in various diseases. Since CKD-specific stressors, such as uremia, chronic inflammation, and oxidative stress, are closely associated with altered DNA methylation, epigenetic alterations in inflammatory and longevity-related genes likely drive disease progression and patient prognosis. This study aims to evaluate the relationship between targeted DNA methylation and complications in CKD patients(both non-dialysis and dialysis-dependent phases)compared to healthy controls.

Basic objectives2

Others

Basic objectives -Others

The primary endpoint is defined as a composite of fatal and non-fatal cardiovascular disease and mortality. The secondary endpoints include: 1)nutritional disorders, 2)bone metabolism disorders, 3)anemia, and 4)the rate of renal disease progression. We will investigate the association between these endpoints and the methylation of the promoter region of the target gene.

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Not applicable

Primary outcomes

Composite of fatal and non-fatal cardiovascular disease and mortality

Key secondary outcomes

1)nutritional disorders, 2)bone metabolism disorders, 3)anemia, and 4)the rate of renal disease progression.

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

20

years-old

<=

Age-upper limit

100

years-old

>

Gender

Male and Female

Key inclusion criteria

Hemodialysis Patients: Patients undergoing maintenance hemodialysis at Kawasaki Clinic, Ebara Clinic, Monnaka Kidney Clinic, Toyosu Kidney Clinic, Shibagaki Clinic Jiyugaoka, Shibagaki Clinic Togoshi, Shibagaki Clinic Kugahara, Nagahara Sanwa Clinic, and Yukigaya Sanwa Clinic.
CKD Patients: Patients undergoing treatment at the Department of Nephrology, Showa Medical University Hospital, and the Department of Nephrology, Showa Medical University Koto Toyosu Hospital.
Healthy Controls: Subjects recruited at the Showa Medical University Clinical Pharmacology Research Institute.

Key exclusion criteria

1)Patients under 20 years of age
2)Patients unable to provide written informed consent
3)Patients with advanced cancer, active hepatitis, infectious diseases, or collagen diseases

Target sample size

250

Name of lead principal investigator

1st name	Hirokazu
Middle name
Last name	Honda

Organization

Showa Medical University Graduate School of Medicine

Division name

Department of Nephrology

Zip code

142-8666

Address

1-5-8, Hatanodai, Shinagawa-ku, Tokyo, Japan

TEL

03-3784-8533

Email

hondah@med.showa-u.ac.jp

Name of contact person

1st name	Hirokazu
Middle name
Last name	Honda

Organization

Showa Medical University Graduate School of Medicine

Division name

Department of Nephrology

Zip code

142-8666

Address

1-5-8, Hatanodai, Shinagawa-ku, Tokyo, Japan

TEL

03-3784-8533

Homepage URL

Email

hondah@med.showa-u.ac.jp

Institute

Showa Medical University

Institute

Department

Personal name

Organization

Japan Science and Technology Agency

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Showa Medical University Research Ethics Review Board

Address

1-5-8 Hatanodai, Shinagawa-ku, Tokyo

Tel

03-3784-8863

Email

surac1@ofc.showa-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

Not Applicable

Institutions

Date of disclosure of the study information

2026

Year

05

Month

22

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Enrolling by invitation

Date of protocol fixation

2013

Year

11

Month

08

Day

Date of IRB

2013

Year

11

Month

08

Day

Anticipated trial start date

2016

Year

05

Month

30

Day

Last follow-up date

2028

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This study was initially designed as a research protocol for methylation analysis in dialysis patients; the first version was finalized and approved by the institutional review board in November 2013. Patient enrollment subsequently began in May 2016. The collected samples were cryopreserved at -80 degrees C until the required number of cases was reached, allowing for batch analysis of DNA and other components.
Thereafter, the protocol underwent multiple revisions due to the addition of non-dialysis chronic kidney disease (CKD) patients and healthy subjects to the study population, the introduction of new DNA methylation analysis methods, and a change in our institution's name. However, the primary endpoints, secondary endpoints, and the evaluation period remained unchanged.
Because this study was initiated as a non-interventional observational study, it was not initially registered in a clinical trial registry. Subsequently, the target population was expanded, and targeted gene methylation analysis using droplet digital PCR (ddPCR) became feasible, which led to a protocol revision. Furthermore, as we are considering the future addition of comprehensive methylation analysis using whole-genome bisulfite sequencing (WGBS), we newly registered the study in the UMIN Clinical Trials Registry (UMIN-CTR) to enhance the objective transparency and reliability of the overall research.
Importantly, at the time of this UMIN registration, the eligibility criteria for the target patients and the definitions of the primary and secondary endpoints (clinical outcomes) were kept completely identical to the initial plan. Therefore, there are no arbitrary protocol modifications (bias) driven by post-hoc data analysis results.

Registered date

2026

Year

05

Month

19

Day

Last modified on

2026

Year

05

Month

20

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000070514