UMIN-ICDS Clinical Trial

Public title

Development of a diagnostic system for precision medicine in refractory vascular anomalies

Acronym

VA-EP Study

Scientific Title

Development of a diagnostic system for precision medicine in refractory vascular anomalies: a multicenter observational and human genome/gene analysis study using a Vascular Anomaly Expert Panel (VA-EP)

Scientific Title:Acronym

Vascular Anomaly Expert Panel (VA-EP) Study

Region

Japan

Condition

Refractory vascular anomalies (vascular tumors and vascular malformations) as defined by the ISSVA classification, including generalized lymphatic anomaly, Gorham-Stout disease, lymphatic malformation, venous malformation, arteriovenous malformation, Klippel-Trenaunay-Weber syndrome, Sturge-Weber syndrome, blue rubber bleb nevus syndrome, and Kasabach-Merritt phenomenon

Classification by specialty

Medicine in general	Gastroenterology	Hematology and clinical oncology
Surgery in general	Pediatrics	Dermatology
Orthopedics	Radiology	Neurosurgery
Plastic surgery	Aesthetic surgery

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

In collaboration with the Japanese Society for the Study of Vascular Anomalies (JSSVA) and related research groups, this study aims (1) to establish a multidisciplinary Vascular Anomaly Expert Panel (VA-EP) that integrates clinical, imaging, pathological, and genetic information to improve diagnostic accuracy and standardize treatment decisions; (2) to develop standard operating procedures for genetic analysis of FFPE and frozen specimens; (3) to develop a highly sensitive method for detecting low-VAF variants by enrichment of lesional endothelial cells with CD31 sorting; (4) to evaluate the clinical applicability of cfDNA-based liquid biopsy; (5) to build a patient-centered model for returning genetic results by comparing return methods using patient-reported outcomes (PROs); and (6) to provide information in partnership with patient organizations. Through these activities, the study will build a diagnostic system for precision medicine in refractory vascular anomalies.

Basic objectives2

Others

Basic objectives -Others

Improvement of diagnostic accuracy and standardization of diagnosis and treatment decisions (evaluation of the rate of diagnostic change by the VA-EP)

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Rate of diagnostic change by the VA-EP compared with the conventional diagnosis

Key secondary outcomes

(1) Variant detection rate by specimen type and analytical method; (2) rate of change in treatment strategy before and after VA-EP review; (3) change in VAF before and after CD31 sorting; (4) concordance between cfDNA and tissue analysis (kappa coefficient); (5) comprehension score (scaled 0-100), satisfaction with the explanation, and psychological distress (Japanese versions of K6 and SDQ) by method of returning genetic results; (6) proportion of participants who wished disclosure among those asked about disclosure (disclosure preference rate); (7) association between genetic variants and clinical phenotype (disease, lesion site); (8) association between genetic variants and treatment response

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

Not applicable

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

(1) Patients clinically diagnosed with, or strongly suspected of having, refractory vascular anomalies (vascular tumors or vascular malformations) according to the ISSVA classification, including generalized lymphatic anomaly, Gorham-Stout disease, lymphatic malformation, venous malformation, arteriovenous malformation, Klippel-Trenaunay-Weber syndrome, Sturge-Weber syndrome, blue rubber bleb nevus syndrome, and Kasabach-Merritt phenomenon.
(2) Patients from whom tissue (frozen or FFPE), blood, or body fluid (lymph, cyst fluid, pleural effusion, ascites, etc.) specimens are obtained for diagnostic or therapeutic purposes, or have already been obtained and stored.
(3) Patients meeting any of the following: (a) written informed consent obtained from the patient or a legally authorized representative; (b) patients whose specimens/data were obtained in the prior studies specified in the protocol, where the original consent covers use in this study or an opt-out procedure has been implemented at the providing institution without refusal; (c) patients whose existing specimens are used under an opt-out procedure at the providing institution without refusal.

Key exclusion criteria

(1) Patients (or their legally authorized representatives) who do not consent to participation, or who refuse research use under the opt-out procedure.
(2) Patients for whom tissue, blood, or body fluid specimens of adequate quality or quantity for analysis cannot be secured.
(3) Patients judged by the principal investigator or co-investigators to be inappropriate for participation.

Target sample size

450

Name of lead principal investigator

1st name	Michio
Middle name
Last name	Ozeki

Organization

Gifu University Graduate School of Medicine

Division name

Department of Pediatrics

Zip code

5011194

Address

1-1 Yanagido, Gifu City 501-1194, Japan

TEL

0582306000

Email

ozeki.michio.j5@f.gifu-u.ac.jp

Name of contact person

1st name	Michio
Middle name
Last name	Ozeki

Organization

Gifu University Hospital

Division name

Department of Pediatrics

Zip code

5011194

Address

1-1 Yanagido, Gifu City 501-1194, Japan

TEL

0582306000

Homepage URL

https://www.hosp.gifu-u.ac.jp/medical/shoni/

Email

ozeki.michio.j5@f.gifu-u.ac.jp

Institute

Department of Pediatrics, Gifu University Graduate School of Medicine

Institute

Department

Personal name

Michio Ozeki

Organization

Japan Agency for Medical Research and Development (AMED), Practical Research Project for Rare/Intractable Diseases (Grant No. 26ek0109864h0001)

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Japan

Co-sponsor

Tohoku University Graduate School of Medicine; Keio University School of Medicine; Hokkaido University Graduate School of Medicine; Wakayama Medical University; Osaka University Graduate School of Medicine; National Hospital Organization Osaka National Hospital; Shinshu University School of Medicine; National Defense Medical College; Saitama Children's Medical Center (9 collaborating institutions)

Name of secondary funder(s)

Gifu University (operating grant)

Organization

Medical Research Ethics Committee, Gifu University Graduate School of Medicine

Address

1-1 yanagito Gifu-shi

Tel

0582306000

Email

ozeki.michio.j5@f.gifu-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

岐阜大学医学部附属病院および、東北大学大学院医学系研究科、慶應義塾大学医学部、北海道大学大学院医学研究院、和歌山県立医科大学医学部、大阪大学大学院医学系研究科、独立行政法人国立病院機構大阪医療センター、信州大学学術研究院医学系、防衛医科大学校、埼玉県立小児医療センター

Date of disclosure of the study information

2026

Year

09

Month

07

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

Open public recruiting

Date of protocol fixation

2026

Year

08

Month

16

Day

Date of IRB

2026

Year

09

Month

02

Day

Anticipated trial start date

2026

Year

09

Month

07

Day

Last follow-up date

2029

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This is an observational study and a human genome/gene analysis study, including a retrospective component using existing specimens and data. Enrollment continues until March 31, 2028; the observation period ends March 31, 2029; and the overall study period ends March 31, 2032 (including publication). Part of the genetic analysis is outsourced to Thermo Fisher Scientific K.K. (targeted panel sequencing) and Cancer Precision Medicine Inc. (cfDNA analysis and digital PCR). The PRO sub-study on returning genetic results is exploratory; the return method is chosen by the participant (or representative) in consultation with the attending physician, without allocation by investigators.

Registered date

2026

Year

09

Month

07

Day

Last modified on

2026

Year

09

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071937