Aromatase Inhibitor in Bone Maturation, Children With Silver Russell or Prader-Willi Syndrome

• Status: Unknown status
• Trial end date: 2016-10-01
• Target enrollment: 0
• Participant gender: All

Summary

There is currently no drug with pediatric marketing authorization capable of limiting the advance in bone maturation of children with aggressive adrenarche. Estrogens are the principal actors involved in bone maturation and premature epiphyseal fusion. Aromatase inhibitors, used for the treatment of hormone-dependent cancers, block the transformation of androgens into estrogens. Third generation inhibitors, of which Anastrozole is one, appear to be well tolerated in children and are sometimes used within the framework of clinical trials to limit bone maturation and improve prognosis with respect to final size, notably in children treated with growth hormone (GH) due to a GH deficit. Nevertheless, the data reported are based on small sample sizes and do not include children with pathological adrenarche.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Anastrozole; Aromatase Inhibitors

Criteria

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.