Clinical trial NCT02790112: Long-term Outcome of GnRH Analogues Treatment of Children With Idiopathic Central Precocious Puberty
Official title: Influence of Early Adiposity Rebound, Genetic Polymorphisms and GnRHa Treatment on Long-term Outcome of Girls With Idiopathic Central Precocious Puberty.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Puberty, Precocious
Adiposity
Keywords: Body Mass Index
Body Composition
Glucose Metabolism Disorders
Bone Development
Gonadal Disorders
Fertility
Overweight
Obesity
Menarche
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
Collaborators: name: Belgian Study Group for Pediatric Endocrinology
First posted: 2016-06-03
Enrollment: 418
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Single nucleotide polymorphisms (SNP) analyses
timeFrame: 1 day
Secondary outcomes:
measure: Adult height in meters
timeFrame: 1 day
measure: Body mass index in kg/m2
timeFrame: 1 day
measure: Body composition in %
timeFrame: 1 day
measure: Glucose in mg/dl
timeFrame: 1 day
measure: Total Cholesterol in mg/dl
timeFrame: 1 day
measure: LDL-Cholesterol in mg/dl
timeFrame: 1 day
measure: HDL-Cholesterol in mg/dl
timeFrame: 1 day
measure: Insulin in microU/ml
timeFrame: 1 day
measure: Total bone mineralization in Tscore
timeFrame: 1 day
measure: Lumbar bone mineralization in Tscore
timeFrame: 1 day
measure: Femoral neck bone mineralization in Tscore
timeFrame: 1 day
measure: Ovaries volume in ml
timeFrame: 1 day
measure: Ovaries follicles diameter in mm
timeFrame: 1 day
measure: Chronic anovulation in number
timeFrame: 1 day
measure: SHBG by nmol/l
timeFrame: 1 day
measure: Total serum testosterone by ng/dl
timeFrame: 1 day
measure: Ovaries follicles counting
timeFrame: 1 day
measure: Abdominal perimeter in cm
timeFrame: 1 day
measure: Hip perimeter in cm
timeFrame: 1 day
measure: Blood pressure in mmHg
timeFrame: 1 day
measure: Testicular volume in ml
timeFrame: 1 day
measure: LH in IU/L
timeFrame: 1 day
measure: FSH in IU/L
timeFrame: 1 day
measure: Oestradiol in ng/dl
timeFrame: 1 day
measure: DHEAS in micromol/l
timeFrame: 1 day
measure: 17 hydroxyprogesterone in ng/ml
timeFrame: 1 day
measure: Anti-Müllerian Hormone in ng/ml
timeFrame: 1 day
measure: Inhibine in pg/ml
timeFrame: 1 day
measure: Prolactine in microgr/L
timeFrame: 1 day
measure: Uterine diameter in mm
timeFrame: 1 day
measure: Uterine volume in ml
timeFrame: 1 day
measure: Endometrius thickness in mm
timeFrame: 1 day
Other outcomes:
measure: Quality of life
timeFrame: 1 day
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
Study officials:
affiliation: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
name: Constanza Navarro Moreno, D
role: PRINCIPAL_INVESTIGATOR
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