UMIN-CTR Clinical Trial

Public title

Case-control study of Autoimmune hepatitis and Primary Biliary Cholangitis

Acronym

Case-control study of Autoimmune hepatitis and Primary Biliary Cholangitis

Scientific Title

Case-control study of Autoimmune hepatitis and Primary Biliary Cholangitis

Scientific Title:Acronym

Case-control study of Autoimmune hepatitis and Primary Biliary Cholangitis

Region

Japan

Condition

Autoimmune hepatitis
Primary Biliary Cholangitis

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Purpose of identifying environmental factors involved in the development of PBC and AIH

Basic objectives2

Others

Basic objectives -Others

Identification of disease-causing factors

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Incidence of diseases affected by environmental factors (Artificial statistical / socio-economic characteristics, lifestyle, medical history, family history, surgical history, vaccination history, women's events)

Key secondary outcomes

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

Not applicable

Gender

Male and Female

Key inclusion criteria

Case
Primary Biliary Cholangitis or Autoimmune hepatitis was confirmed by the diagnostic criteria of the "Investigative Research on The Intractable Hepato-Biliary Diseases" group of the Health Labor Science research Grants from Research on Measures for intractable Diseases, and is currently at Teikyo University Hospital, or Among patients who are outpatients or inpatients to other facilities belonging to the research organization of this study, those who have consented to participate in this study.

Control
Patients who meet the following three conditions and are currently outpatient or inpatient at Teikyo University Hospital or another facility belonging to the research organization of this research.
The gender and age of the patient match.
Not suffering from PBC, AIH, and other autoimmune diseases.
A member of the research organization is the attending physician.

Key exclusion criteria

PBC/AIH atypical cases or overlapping cases. Patients under 20 years old.
Other patients who are judged to be inappropriate for research participation.

Target sample size

1500

Name of lead principal investigator

1st name	Atsushi
Middle name
Last name	Tanaka

Organization

Teikyo University School of Medicine

Division name

Internal medicine

Zip code

173-8605

Address

2-11-1 Kaga, Itabashi City, Tokyo 173-8605

TEL

03-3964-1211

Email

a-tanaka@med.teikyo-u.ac.jp

Name of contact person

1st name	Kosuke
Middle name
Last name	Matsumoto

Organization

Teikyo University School of Medicine

Division name

Internal medicine

Zip code

173-8605

Address

2-11-1 Kaga, Itabashi City, Tokyo 173-8605

TEL

03-3964-1211

Homepage URL

Email

m-kosuke0716@med.teikyo-u.ac.jp

Institute

Teikyo University School of Medicine

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Teikyo University Medical Research Ethics Committee

Address

2-11-1 Kaga, Itabashi City, Tokyo 173-8605

Tel

03-3964-7256

Email

turb-office@teikyo-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

2021

Year

01

Month

09

Day

URL releasing protocol

https://link.springer.com/article/10.1007/s00535-021-01836-6

Publication of results

Published

URL related to results and publications

https://link.springer.com/article/10.1007/s00535-021-01836-6

Number of participants that the trial has enrolled

1096

Results

The identified factors were vault toilet at home in childhood, unpaved roads around the house in childhood, ever smoking, and hair dye use in the model for lifestyle factors, and a history of any type of autoimmune disease, a history of Cesarean section, and presence of PBC in first-degree relatives in the model for medical and familial factors.

Results date posted

2023

Year

01

Month

10

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

2021

Year

11

Month

18

Day

Baseline Characteristics

Eligible cases were patients who were diagnosed with PBC aged over 20 years old. PBC was diagnosed according to the criteria established by the Japanese Intractable Hepatobiliary Disease Study Group. The patients with PBC were consecutively asked to participate in this study at the outpatient clinic or during admission, and 548 patients with PBC. Overlap cases with autoimmune hepatitis and cases with viral hepatitis as comorbidities were excluded from this study. However, PBC patients with other etiologies associated with lifestyle (alcoholic liver disease and non-alcoholic fatty liver disease) were included in the study.
As a control, 548 age-and sex-matched individuals (range of 5 years) who visited the same center at the same time (within 2 months) for a disease other than PBC and any autoimmune disease were invited to participate in the study. Each cooperating center was asked to provide at least one pair of participants, the case and control.

Participant flow

Completed and returned the questionnaires with respect to demographic and lifestyle factors and past and family history, and reproductive history in women, after giving their informed consent.

Adverse events

Did not occur in particular.

Outcome measures

The patient's self-administered questionnaires included 121 items, as follows: 1) demographic, anthropometric, and socioeconomic features; 2) lifestyle; 3) past history of autoimmune diseases, non-autoimmune diseases, surgery, and vaccinations; 4) history of autoimmune diseases in first-degree relatives (FDRs); and 5) reproductive history in female individuals. Most of these items were included in the questionnaires since previous studies had utilized these and identified some of them as environmental factors that were significantly associated with PBC. In addition, several items (vault toilet at home in childhood, Japanese-style toilet at home in childhood, ditches around the house in childhood, and unpaved roads around the house in childhood) were included in the current study to adjust with the Japanese environment.
Comparisons between cases and controls for potential associations were conducted using the nonparametric Wilcoxon test for continuous variables and the chi-square test and Fisher's exact test for categorical variables. Factors with statistically significant differences in unadjusted bivariate analyses were entered into backward stepwise conditional multiple logistic regressions. We developed two different models as in a previous study : the first was a model for lifestyle factors, and the second was a model for factors in terms of medical and familial history. Each model was adjusted for putative explanatory variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to determine significance.
All analyses were two-sided, and the level of significance was set at P<0.05. Continuous variables are expressed as median (interquartile range (IQR)), and categorical variables are expressed as percentages. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 28.0.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2020

Year

08

Month

06

Day

Date of IRB

2020

Year

08

Month

06

Day

Anticipated trial start date

2020

Year

12

Month

01

Day

Last follow-up date

2021

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Research method

Ask study participants who have agreed in writing to participate in the study to access the constructed Electronic Data Capture System and enter answers to the questions related to the listed environmental factors. Participants who have difficulty using EDC will be asked to distribute a questionnaire and return envelope, fill it out, and mail it.
Integrate the information entered into the EDC by study participants and the information in the mailed questionnaire and statistically compare AIH patients with control patients and PBC patients with control patients.

Registered date

2021

Year

01

Month

09

Day

Last modified on

2023

Year

01

Month

10

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049036