Trial record 2 of 2 for:    "Russell-Silver syndrome"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01520467
First received: January 25, 2012
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention
Silver Russell Syndrome
Prader-Willi Syndrome
Drug: Anastrozole
Drug: Placebo

Study Type: 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
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • metabolic impact (monitoring of body composition by bi photonic absorptiometry, lipid, glucose, HbA1c, insulin and HOMA-IR profiles, leptin). [ Time Frame: baseline, 6, 12 and 18 months ] [ Designated as safety issue: Yes ]
  • impact on bone (X-ray of the dorsolumbar spine, bi photonic absorptiometry, blood-borne markers of bone remodeling). [ Time Frame: 18 months, and earlier in case of bone pain ] [ Designated as safety issue: Yes ]
  • impact on the gonadotropic axis [ Time Frame: baseline, 6, 12 and 18 months ] [ Designated as safety issue: Yes ]
  • impact on the somatotropic axis (growth rate, IGF-1, IGFBP3). [ Time Frame: baseline, 6, 12 and 18 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: April 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anastrozole
stratification according to the rare disease. Oral administration of Anastrozole (1mg/day) for 18 months
Drug: Anastrozole
Anastrozole (1mg/day), administered orally for 18 months
Other Name: Anastrozole
Placebo Comparator: Placebo
stratification according to the rare disease. Oral administration of 1 placebo tablet /day for 18 months
Drug: Placebo
1 placebo tablet /day administered orally for 18 months.
Other Name: Placebo

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   5 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520467

Contacts
Contact: Irène Netchine, MD, PhD + 33 (0) 1 44 73 66 31 irene.netchine@trs.aphp.fr

Locations
France
Explorations Fonctionnelles d'Endocrinologie - Centre de Référence des Maladies Endocriniennes Rares de la Croissance Hôpital Armand Trousseau Recruiting
Paris, France, 75012
Contact: Irène Netchine, MD, PhD    + 33 (0) 1 44 73 66 31    irene.netchine@trs.aphp.fr   
Principal Investigator: Irène Netchine, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Irène Netchine, MD, PhD Assistance Publique
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01520467     History of Changes
Other Study ID Numbers: P 100129, AOM 10093
Study First Received: January 25, 2012
Last Updated: November 14, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority

Keywords provided by Assistance Publique - Hôpitaux de Paris:
SRS
PWS
pathological adrenarche
aromatase inhibitor
Children

Additional relevant MeSH terms:
Silver-Russell Syndrome
Prader-Willi Syndrome
Syndrome
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Obesity
Overnutrition
Nutrition Disorders
Disease
Pathologic Processes
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Musculoskeletal Diseases
Dwarfism
Aromatase Inhibitors
Anastrozole
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014