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

NCT01520467 | Unknown DMC

• 2 other identifiers: P 100129AOM 10093
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Silver Russell Syndrome; Prader-Willi Syndrome

Keywords

SRS; PWS; pathological adrenarche; aromatase inhibitor; Children

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  18 months

Secondary Outcomes (4)

• metabolic impact (monitoring of body composition by bi photonic absorptiometry, lipid, glucose, HbA1c, insulin and HOMA-IR profiles, leptin).

  baseline, 6, 12 and 18 months

• impact on bone (X-ray of the dorsolumbar spine, bi photonic absorptiometry, blood-borne markers of bone remodeling).

  18 months, and earlier in case of bone pain

• impact on the gonadotropic axis

  baseline, 6, 12 and 18 months

• impact on the somatotropic axis (growth rate, IGF-1, IGFBP3).

  baseline, 6, 12 and 18 months

Study Arms (2)

Anastrozole

EXPERIMENTAL

stratification according to the rare disease. Oral administration of Anastrozole (1mg/day) for 18 months

Drug: Anastrozole

Placebo

PLACEBO COMPARATOR

stratification according to the rare disease. Oral administration of 1 placebo tablet /day for 18 months

Drug: Placebo

Interventions

Anastrozole DRUG

Anastrozole (1mg/day), administered orally for 18 months

Anastrozole

Placebo DRUG

1 placebo tablet /day administered orally for 18 months.

Placebo

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• Patients should be capable of swallowing pills of the same size as the experimental drug.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Explorations Fonctionnelles d'Endocrinologie - Centre de Référence des Maladies Endocriniennes Rares de la Croissance Hôpital Armand Trousseau

Paris, 75012, France

Location

MeSH Terms

Conditions

Silver-Russell Syndrome; Prader-Willi Syndrome

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Dwarfism; Imprinting Disorders; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Irène Netchine, MD, PhD

  Assistance Publique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2012
• First Posted: January 30, 2012
• Study Start: April 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: October 1, 2016
• Last Updated: August 24, 2016

Record last verified: 2016-08

Locations

FR (1)