Efficacy and Tolerance of Treatment With an Aromatase Inhibitor (Anastrozole) to Limit the Progression of Bone Maturation Related to Pathological Adrenarche in Children With Silver-Russell or Prader-Willi Syndrome
5 Years
12 Years
Both
Silver Russell Syndrome, Prader-Willi Syndrome
Trial Information
Efficacy and Tolerance of Treatment With an Aromatase Inhibitor (Anastrozole) to Limit the Progression of Bone Maturation Related to Pathological Adrenarche in Children With Silver-Russell or Prader-Willi Syndrome
Silver-Russell syndrome (SRS), which occurs secondary to an imprinting disorder due to the
anomalous methylation of chromosome 11 or due to a uniparental disomy of chromosome 7, is a
rare syndrome (ORPHA813, OMIM 180860) characterized by growth retardation with an
intrauterine onset, a normal head circumference, small postnatal size and major feeding
difficulties. Starting at a very young age, the rapid aging of bone can occur even in the
absence of central puberty, in association with the production of androgens by the adrenal
glands (adrenarche). This advanced bone maturation can compromise final size, even when the
child receives growth hormone (GH) treatment for several years.
Prader-Willi syndrome (PWS) is also a rare disease (ORPHA739, OMIM 176270), occurring
secondary to an imprinting disorder due to an anomaly in chromosome 15 (paternal deletion or
maternal disomy). These children also present feeding difficulties during the first few
years of life, as well as small size. They are frequently treated with GH, and their bone
age can increase during the course of adrenarche, as in certain patients with SRS.
Inclusion Criteria:
- Patients with genetically proven SRS or PWS, under treatment with GH in the usual
context of the disease, presenting with adrenarche (defined either by DHEAS levels as
a function of age or by the appearance of pubic hair) associated with a bone age at
least 6 months greater than chronological age and in the absence of the onset of
central puberty (LH peak ≤ LH peak in prepubertal patients, according to the
standards of the laboratory performing the GnRH stimulation test for LH and FSH, and
dating back to less than 3 months).
- Patients with medical coverage.
- The lower age limit for inclusion is 5 years and the upper age limit is 10 complete
years for girls and 12 complete years for boys.
- The maximum body-mass index (BMI) Z-score for inclusion is +4
- Patients should be capable of swallowing pills of the same size as the experimental
drug.
Exclusion Criteria:
- Renal insufficiency (creatinine clearance, calculated according to the Schwartz
formula, lower than 70ml/min/l, 73 m²),
- Hepatic insufficiency (prothrombin ratio < 50% and factor V < 50%),
- Hepatic cytolysis (liver transaminases levels greater than twice the normal level for
age), cholestasis (gamma-glutamyl transferase (GGT) levels greater than twice the
normal level for age),
- Contraindication to one of the components of Anastrozole or the placebo.
- Patients with scoliosis requiring surgery.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Outcome Measure:
The rate of success in each of the two groups, evaluated using an X-ray of the left hand and wrist. Success is defined as a difference in the rate of progression of bone maturation of at least 9 months after 18 months of treatment.
Outcome Description:
Principal objective: To evaluate the efficacy of Anastrozole compared to placebo in slowing bone maturation during pathological adrenarche in children with SRS or PWS. Principal criterion of evaluation: The rate of success in each of the two groups, evaluated using an X-ray of the left hand and wrist. Success is defined as a difference in the rate of progression of bone maturation of at least 9 months after 18 months of treatment.
Outcome Time Frame:
18 months
Safety Issue:
Yes
Principal Investigator
Irène Netchine, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Assistance Publique
Authority:
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Study ID:
P 100129
NCT ID:
NCT01520467
Start Date:
April 2012
Completion Date:
July 2015
Related Keywords:
- Silver Russell Syndrome
- Prader-Willi Syndrome
- SRS
- PWS
- pathological adrenarche
- aromatase inhibitor
- Children
- Prader-Willi Syndrome
- Silver-Russell Syndrome
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