UMIN-CTR Clinical Trial

Public title

Multicenter observational studies for lipoid congenital adrenal hyperplasia in Japan

Acronym

LCAH-J

Scientific Title

Establishment of a patient registry system and multicenter observational studies for lipoid congenital adrenal hyperplasia in Japan

Scientific Title:Acronym

LCAH-J

Region

Japan

Condition

Lipoid congenital adrenal hyperplasia

Classification by specialty

Endocrinology and Metabolism

Pediatrics

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

The purpose of the study is to establish a Japanese patient registry and to accumulate evidence, helping develop clinical practice guidelines for LCAH. The evidence includes the prevalence, incidence, age at onset, or risk factor for obesity, hypertension, glucose intolerance, diabetes mellitus, osteoporosis, hypogonadism, or ovarian cysts or torsion. The evidence will be derived from a prospective observational study in cooperation with the registry. The study focuses on the following clinical questions (CQ) raised by the research group for adrenal disorders: CQ1 Is it possible to predict the risks of adverse effects of glucocorticoid supplementation? Any optimization of glucocorticoid supplementation to reduce the risk of adverse effects?; CQ2 Is it possible to predict the risk of premature ovarian failure among female patients?; CQ3 Is it possible to predict the risk of ovarian cysts or torsion among female patients? Any strategy to reduce or circumvent the risk of ovarian cysts or torsion?; CQ4 Is it possible to predict the risk of androgen deficiency or spermatogenesis defect among non-classic LCAH male patients?

Basic objectives2

Others

Basic objectives -Others

The expected achievements of this study are to establish a patient registry, that will be available for future cohort study or intervention study assessing new treatment strategies, and to provide recommendation on each CQ to develop a high-quality clinical practice guideline for LCAH. The recommendations will enhance the quality of management for patients with LCAH including optimization of glucocorticoid supplementation to reduce adverse effects and accurate prediction of prognosis of gonadal function or risk for ovarian cysts or torsion to enable preemptive medicine.

Trial characteristics_1

Others

Trial characteristics_2

Others

Developmental phase

Not applicable

Primary outcomes

1) Incidence (or prevalence), onset ages, and risk factors of commodities for glucocorticoid replacement therapy
Commodities such as obesity, hypertension, impaired glucose tolerance, diabetes mellitus, or osteoporosis were assessed.

2) Incidence (or prevalence), onset ages, and risk factors of commodities for ovarian function and other anatomical abnormalities
Secondary sexual characteristics, premature ovarian failure, and ovarian hypertrophy, cyst, or torsion in 46,XX female cases were assessed.

3) Incidence (or prevalence), onset ages, and risk factors of commodities for testicular function
Secondary sexual characteristics and spermatogenesis in 46,XY male cases were assessed.

Key secondary outcomes

1) Protective or risk factors for health-related quality of life (QOL)
Scores of SF36 health survey v2 (Japanese version) were assessed with other factors including age, STAR genotype, sex of raring, and amount or type of glucocorticoid or sex steroids for replacement therapy.

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

This study enrolls patients with lipoid congenital adrenal hyperplasia who met the following criteria as "definite" or "probable" and provide the informed consent.

Criteria for lipoid congenital adrenal hyperplasia
Definite: I + II + III + V or I + II + IV + V
Probable: I + II + V

I. Clinical manifestation
1) Signs related to adrenal insufficiency: poor appetite, failure to thrive, nausea/vomit, dehydration, impaired consciousness, or shock.
2) Hyperpigmentation: generalized skin, gingiva, lips, areola, umbilicus, or genitalia.
3) Undermasculinization of the external genitalia in 46,XY cases: Mostly severe as female-type external genitalia, rarely mild as hypospadias or micropenis.
4) Hypergonadotropic hypogonadism: delayed puberty, stunted pubertal progression, secondary menarche.

II. Laboratory data
1) Deficiency of adrenocortical steroid hormones
(1) Low serum cortisol level
(2) Low serum or plasma aldosterone level
(3) Low serum adrenal androgen level
(4) Low urinary metabolites of adrenocortical steroid hormones, especially those derived from fetal cortex
2) High plasma ACTH level
3) High plasma renin level
4) Low serum sodium, high serum potassium, or low plasma glucose level
5) High serum LH and FSH levels

III. Imaging study (abdominal CT)
Adrenal swelling with fat density

IV. Genetic analysis
Pathogenic STAR variants

V. Exclusion
Congenital adrenal hypolpasia, ACTH unresponsiveness, 21-hydroxylase deficiency, 3beta-hydoroxysteroid dehydrogenase deficiency

Key exclusion criteria

The study dose not enroll patients who have other disorders causing obesity, hypertension, impaired glucose tolerance, diabetes mellitus, osteoporosis, or hypogonadism or those whom their physicians or principal investigator decide inappropriate for this study.

Target sample size

80

Name of lead principal investigator

1st name	Tomohiro
Middle name
Last name	Ishii

Organization

Keio University School of Medicine

Division name

Department of Pediatrics

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, JAPAN

TEL

03-3353-1211

Email

tishii@1992.jukuin.keio.ac.jp

Name of contact person

1st name	Tomohiro
Middle name
Last name	Ishii

Organization

Keio University School of Medicine

Division name

Department of Pediatrics

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, JAPAN

TEL

03-3353-1211

Homepage URL

Email

tishii@1992.jukuin.keio.ac.jp

Institute

Keio University School of Medicine

Institute

Department

Personal name

Tomohiro Ishii

Organization

AMED

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

The Ethics Committee of the Keio University School of Medicine

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, JAPAN

Tel

03-3353-1211

Email

med-rinri-ft_pt@adst.keio.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

慶應義塾大学病院、都立小児総合医療センター、あいち小児保健医療総合センター、大分大学、自治医科大学とちぎこども医療センター、福島県立医科大学、東京女子医科大学、徳島大学、浜松医科大学、秋田大学、大阪母子医療センター、聖マリアンナ医科大学横浜市西部病院、新潟大学医歯学総合病院、太田記念病院、大阪大学、名古屋市立大学病院、国立成育医療研究センター、さいたま市立病院、九州大学病院、静岡市立清水病院、金沢大学、東京歯科大学市川総合病院、信州大学など

Date of disclosure of the study information

2023

Year

04

Month

01

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

Preinitiation

Date of protocol fixation

2022

Year

12

Month

14

Day

Date of IRB

2023

Year

02

Month

07

Day

Anticipated trial start date

2023

Year

04

Month

01

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 multicenter observational study will collect and analyze the following data every 6 month since the enrollment.

1) Baseline characteristics
DOB, sex, smoking or drinking history, past medical history, co-morbidities, food or drug allergy, pregnant or delivery history (spouse), transition, sex chromosome, and STAR genotype.

2) Physical examination
Blood pressure, height, weight, abdominal circumference, breast or pubic hair development (Tanner stage), menstrual cycle (female), stretched penile length (male), and testicular volume (male).

3) Laboratory examination
Blood chemistry (AST, ALT, LDH, ALP, UN, Cr, UA, Na, K, Cl, Ca, IP, Glu, HbA1c, LDL-C, HDL-C, TG), endocrinological tests (plasma ACTH, plasma renin, serum LH, FSH, estradiol, progesterone, AMH, testosterone, cortisol, aldosterone, 25-OH vitamin D, BAP, TRACP-5b), Urine chemistry (Cr, Ca, IP), semen analysis (ejaculate volumed, sperm concentration, sperm morphology, total motility)

4) Imaging study
Gonad, uterus.

5) Bone mineral density

6) Treatment
Type or amounts of medication.

7) Health-related quality of life (QOL)
SF-36 health survey v2 (Japanese version).

Registered date

2023

Year

02

Month

28

Day

Last modified on

2023

Year

02

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000056614