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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Puberty, Precocious; Environmental Exposure; Breast
• Intervention / Treatment: Other: Environmental health measures

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marie-Paule LEBITASY; Phone Number: +33 03.20.22.52.69; Email: lebitasy.marie-paule@ghicl.net
• Study Contact Backup: Name: Elodie MOUTAILLER; Phone Number: +33 03.20.22.52.69; Email: moutailler.elodie@ghicl.net

Study Locations

• France
  • Nord Pas De Calais
    • Lambersart, Nord Pas De Calais, France, 59130
      • Recruiting
      • Cabinet BLM
      • Contact: Patricia RANNAUD-BARTAIRE, PhD; Email: bartaire.patricia@ghicl.net
      • Principal Investigator: Patricia RANNAUD-BARTAIRE
    • Lille, Nord Pas De Calais, France, 59000
      • Recruiting
      • Saint Vincent Hospital
      • Contact: Patricia RANNAUD-BARTAIRE, PhD; Email: bartaire.patricia@ghicl.net
      • Principal Investigator: Patricia RANNAUD-BARTAIRE, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Blood tests; Magnetic Resonance Imaging (MRI); Determination of endocrine disruptors in hair; Urine tests; Bone age x ray

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of endocrine disruptors in hair	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.	Change from baseline at 90 days
Tanner scale	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	Change from baseline at 90 and 180 days
Bone age determination by X ray	Determination of bone age to determine the maturity of the child's skeletal system.	Change from baseline at 90
Degree of severity of teeth hypomineralisation	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	Baseline, 3 months
Follicle-stimulating hormone (FSH) level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Estradiol (E2) level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Testosterone Level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
17 hydroxyprogesterone level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Dehydroepiandrosterone sulfate level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Sex Hormone-Binding Globulin level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Thyroid Stimulating Hormone level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
FT4 (Free Thyroxine hormone) level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Androstenedione level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Insulin level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Glycated hemoglobin (HbA1C) level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Insulin-like Growth Factor-1 level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Leptine level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Luteinizing hormone (LH) level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days
Glycemia level	Blood test for determining the evolution of this parameter from baseline	Change from baseline at 90 days and 180 days

Collaborators and Investigators

• Sponsor: Lille Catholic University
• Investigators: Principal Investigator: Patricia RANNAUD-BARTAIRE, PhD, Hôpital Saint-Vincent de Paul

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2023
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2027

Study Registration Dates

• First Submitted: October 4, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Endocrine disruptors; Girls; Early puberty; Breast growth; Environmental Health Measure
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Puberty, Precocious; Physiological Effects of Drugs; Endocrine Disruptors
• Other Study ID Numbers: RT-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No