PENELOPE: Early Breast Growth in Girls Aged 6 to 8 Years in the Current Environmental Context

Sponsor

Lille Catholic University (Other)

Overall Status

Recruiting

CT.gov ID

NCT06083415

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Various studies show an increase in the number of cases of early puberty in girls with breast development with a variable clinical presentation and evolution. This increasing phenomenon concerns girls between 6 and 8 years old. In a large number of cases, from 70 to 95% depending on the series, no medical cause is found and environmental factors are suspected to be involved.

Descriptive studies of these patients are scarce and not always provide an overview of all the parameters in line with the concept of the exposome.

The PENELOPE clinical trial will allow to analyze a large number of parameters, including the adipose tissue, its metabolism, the endocrine disruptors, and the epigenetic modifications, and to study the impact of environmental health measures in the evolution of these parameters.

The data from the analyses of the endocrine disruptors of the patients will be explored in parallel in experimental models (amphibians, murine, cellular) in order to test potential mechanistic hypotheses.

Condition or Disease	Intervention/Treatment	Phase
Puberty, Precocious Breast Environmental Exposure	Other: Environmental health measures	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Early Breast Growth in Girls Aged 6 to 8 Years in the Current Environmental Context: Clinical and Biological Parameters, Level of Impregnation With Endocrine Disruptors and Evaluation of the Impact of Environmental Health Measures

Actual Study Start Date :

May 15, 2023

Anticipated Primary Completion Date :

May 15, 2026

Anticipated Study Completion Date :

May 15, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 6 to 8 years old girls, presenting with a breast flare-up Girls aged 6 to 8 years old with breast flare (isolated or not) and scheduled for pediatric day hospital stay	Other: Environmental health measures MRI will be used to confirm the presence of breast buds, to measure the size of the ovaries and uterus, as well as the fraction of fat mass (abdominal, subcutaneous, liver and bone marrow). The bood and urine tests will allow to measure different biological and metabolic parameters. The presence of endocrine disruptors will be determined in the hair. The bone age x ray will be estimate the maturity of the child's skeletal system. Other Names: Magnetic Resonance Imaging (MRI) Blood tests Determination of endocrine disruptors in hair Urine tests Bone age x ray

Arm

Intervention/Treatment

Experimental: 6 to 8 years old girls, presenting with a breast flare-up

Girls aged 6 to 8 years old with breast flare (isolated or not) and scheduled for pediatric day hospital stay

Other: Environmental health measures

MRI will be used to confirm the presence of breast buds, to measure the size of the ovaries and uterus, as well as the fraction of fat mass (abdominal, subcutaneous, liver and bone marrow). The bood and urine tests will allow to measure different biological and metabolic parameters. The presence of endocrine disruptors will be determined in the hair. The bone age x ray will be estimate the maturity of the child's skeletal system.

Other Names:

Magnetic Resonance Imaging (MRI)

Blood tests

Determination of endocrine disruptors in hair

Urine tests

Bone age x ray

Outcome Measures

Primary Outcome Measures

Change from baseline of the size of the breast development measured by Magnetic Resonance Imaging [Baseline, 3 months]
This parameter will allow to describe the clinical evolution of breast development after application of environmental health measures
Change from baseline of the size of ovaries/uterus measured by Magnetic Resonance Imaging [Baseline, 3 months,]
This parameter will allow to describe the clinical evolution of ovaries and uterus after application of environmental health measures
Change from baseline of the abdominal fat surface measured by Magnetic Resonance Imaging [Baseline, 3 months]
This parameter will allow to describe the clinical evolution of the abdominal fat surface after application of environmental health measures
Change from baseline of the weight [Baseline, 3 months, 6 months]
This parameter will allow to describe the clinical evolution of the weight after application of environmental health measures
Change from baseline of the height [Baseline, 3 months, 6 months]
This parameter will allow to describe the clinical evolution of the height after application of environmental health measures
Body mass index (BMI) [Baseline, 3 months, 6 months]
This parameter will allow to describe the clinical evolution of the BMI after application of environmental health measures

Secondary Outcome Measures

Measurement of endocrine disruptors in hair [Change from baseline at 90 days]
Describe the evolution of the amount of endocrine disruptors in hair after the implementation of environmental health measures. from 70 to 100 mg of hair will cut as close as possible to the scalp at the posterior vertex, and stored at room temperature to measure endocrine disruptors such as parabens, phthalates, bisphenols and pesticides.
Tanner scale [Change from baseline at 90 and 180 days]
The Tanner scale is a scale of physical development as children transition into adolescence and then adulthood. The scale defines physical measurements of development based on external primary and secondary sex characteristics. Breast: Tanner I: no glandular tissue Tanner II: breast bud forms, areola begins to widen Tanner III: breast begins to become more elevated, and extends beyond the borders of the areola, Tanner IV: increased breast sizing and elevation; areola and papilla form a secondary mound projecting from the contour of the surrounding breast Tanner V: breast reaches final adult size Pubis hair: Tanner I: no pubic hair Tanner II: small amount of long, downy hair Tanner III: hair becomes more coarse and curly, and begins to extend laterally Tanner IV: adult-like hair quality, extending across pubis but sparing medial thighs Tanner V: hair extends to medial surface of the thighs
Bone age determination by X ray [Change from baseline at 90]
Determination of bone age to determine the maturity of the child's skeletal system.
Degree of severity of teeth hypomineralisation [Baseline, 3 months]
The dree of severity is determine according to a scale: 1: <30% of the tooth's enamel surface area visibly disrupted, 2: 31 to 49% of the tooth's enamel surface area visibly disrupted, 3: >50% of the tooth's enamel surface area visibly disrupted
Follicle-stimulating hormone (FSH) level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Estradiol (E2) level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Testosterone Level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
17 hydroxyprogesterone level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Dehydroepiandrosterone sulfate level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Sex Hormone-Binding Globulin level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Thyroid Stimulating Hormone level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
FT4 (Free Thyroxine hormone) level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Androstenedione level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Insulin level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Glycated hemoglobin (HbA1C) level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Insulin-like Growth Factor-1 level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Leptine level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Luteinizing hormone (LH) level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline
Glycemia level [Change from baseline at 90 days and 180 days]
Blood test for determining the evolution of this parameter from baseline

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Years to 8 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Girls aged 6 to 8 years
Presenting a breast development (isolated or not)
Undergoing scheduled pediatric day hospital care (HDJ)
Who agree to participate in the study
Whose parents agree to their child's participation in the study
French speaking
Whose parents speak French
Affiliated to social security

Exclusion Criteria:

Organic brain causes of precocious puberty: History of neurocerebral disease (malformations, developmental abnormalities)
Organic causes of precocious puberty: Mac Cune Albright syndrome, ovarian cyst or tumor and adrenal hyperplasia
History of chemotherapy or radiation therapy
Presenting with a communication disorder
Pregnancy
Persons under protective measures
Persons deprived of liberty for judicial or administrative reasons