Long-term Outcome of GnRH Analogues Treatment of Children With Idiopathic Central Precocious Puberty

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Status: Unknown

Conditions: Adiposity; Puberty, Precocious

Treatments: Other: GnRHas

Study type: Interventional

Funder types: Other

Identifiers

NCT02790112

RESEARCH GRANT (Other Grant/Funding Number)

2015/14OCT/549

Details and patient eligibility

About

This study evaluates the influence of early adiposity rebound, genetic polymorphisms and GnRHa treatment on long-term outcome of girls with idiopathic central precocious puberty.

Full description

Gonadotropin-releasing hormone (GnRH) analogs are the mainstay of treatment for central precocious puberty (CPP) since 1985. The relatively short time period elapsed since the introduction of this therapy has not allowed until now to carry out exhaustive studies on the long-term evolution of treated patients. This project will analyze the long-term outcomes of patients with CPP treated or not with GnRHas on adult height, body mass index, body composition, metabolic disorders, bone mineralization, gonadal function, and fertility in comparison to a control group. Overweight before puberty is associated to earlier menarche, and conversely, earlier menarche predispose to adult obesity and metabolic disorders. Nevertheless, it is unclear if adult adiposity is a direct consequence of early puberty or if early puberty is a marker of a predisposition to excess adiposity from prepuberty through adult life. Recent data in rodent models support the hypothesis that early nutritional status determines a risk for both childhood and adult obesity and influences pubertal timing. In girls, early weight gain in childhood has been associated with early menarche. Pattern of growth rather than absolute level of fatness seem to be of most importance. So the first aim of this study is to compare the outcomes of CCP patients with or without an early adiposity rebound and to demonstrate that adiposity rebound more than CPP per se or the GnRHas therapy affect the outcomes. Moreover, recent genome-wide association studies have identified obesity-related gene variants associated with earlier age at menarche. The investigators hypothesized that there might be a genetic basis underlying the early programming of both childhood and adulthood adiposity and puberty timing. The investigators thus aim to determine if those obesity-related gene variants associated with an early but not precocious menarche could also be found in CPP, especially in girls with an early adiposity rebound and if their presence may affect adult health.

Enrollment: 418 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• History of idiopathic CPP (ICPP) treated with GnRHas.
• A diagnosis of CPP made according to the following criteria: 1) secondary pubertal signs (Tanner stage 2) before 8 years in girls and 9 years in boys; 2) accelerated growth velocity (GV); 3) BA advanced for CA ≥ 1 year; 4) GnRH-stimulated peak LH >5 IU/L.
• A diagnosis of idiopathic CPP according the following criteria: 1) no hypothalamic-pituitary organic lesions at magnetic resonance imaging; 2) no known medical condition that might affect the onset of puberty.
• To determine whether the supposed long-term effects of treatment are instead consequences of the disease itself, untreated ICPP girls aged of ≥ 18 years, will also be included. For comparative purposes, age-matched normal (menarche > 10 y) volunteers will be recruited as a control group.

Exclusion criteria

• In the treated ICCP group if 1) treatment with GnRHas for < 2 years; 2) non-compliance; 3) no gonadotropin suppression observed.
• For all patients: 4) small for gestational age; 5) chronic disease and/or treatment; 6) being < 4 years from menarche.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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418 participants in 3 patient groups

GnRHas - Not GnRHas patients

Other group

Description:

Compared long term outcome of treated and untreated patients with idiopathic central precocious puberty : hormonal assessment; DNA for candidate single nucleotide polymorphisms (SNP) analyses; pelvic ultrasound; dual energy x-ray absorptiometry (DXA)

Treatment:

Other: GnRHas

GnRHas - controls patients

Other group

Description:

Compared long term outcome of treated patients with idiopathic central precocious puberty and control patients for: hormonal assessment; DNA for candidate single nucleotide polymorphisms (SNP) analyses; pelvic ultrasound; dual energy x-ray absorptiometry (DXA)

Treatment:

Other: GnRHas

Not GnRHas - Controls patients

Other group

Description:

Compared long term outcome of untreated patients with idiopathic central precocious puberty and control patients for: hormonal assessment; DNA for candidate single nucleotide polymorphisms (SNP) analyses; pelvic ultrasound; dual energy x-ray absorptiometry (DXA)

Treatment:

Other: GnRHas