Silver Russell SyndromeANASILPRANCT01520467
Aromatase Inhibitor in Bone Maturation, Children With Silver Russell or Prader-Willi Syndrome
A study testing Anastrozole in people with Silver Russell Syndrome and Prader-Willi Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 12 years
- Conditions the study is for
- Silver Russell Syndrome, Prader-Willi Syndrome
- What is being tested?
- Anastrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2012to Oct 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
France1 site
Explorations Fonctionnelles d'Endocrinologie - Centre de Référence des Maladies Endocriniennes Rares de la Croissance Hôpital Armand Trousseau
Paris, 75012
About this study
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
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.
Read the 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.
- Conditions
- Silver Russell Syndrome, Prader-Willi Syndrome
- Being tested
- Anastrozole, Placebo
- Keywords
- SRS, PWS, pathological adrenarche, aromatase inhibitor, Children
- Medical subject headings
- Silver-Russell Syndrome, Prader-Willi Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnastrozoleDrug
Anastrozole (1mg/day), administered orally for 18 months
PlaceboDrug
1 placebo tablet /day administered orally for 18 months.
| Study group | Role | What they receive |
|---|---|---|
| Anastrozole | Experimental | stratification according to the rare disease. Oral administration of Anastrozole (1mg/day) for 18 months Receives: Drug: Anastrozole |
| Placebo | Placebo comparator | stratification according to the rare disease. Oral administration of 1 placebo tablet /day for 18 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
Secondary outcomes (4)
metabolic impact (monitoring of body composition by bi photonic absorptiometry, lipid, glucose, HbA1c, insulin and HOMA-IR profiles, leptin).
Measured: baseline, 6, 12 and 18 months
impact on bone (X-ray of the dorsolumbar spine, bi photonic absorptiometry, blood-borne markers of bone remodeling).
Measured: 18 months, and earlier in case of bone pain
impact on the gonadotropic axis
Measured: baseline, 6, 12 and 18 months
impact on the somatotropic axis (growth rate, IGF-1, IGFBP3).
Measured: baseline, 6, 12 and 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2012 (estimated)
- Study startApr 2012
- Primary completionJul 2016
- Study completionOct 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Silver Russell SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Irène Netchine, MD, PhD, Principal investigator, Assistance Publique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01520467
- Sponsor's protocol ID
- P 100129
- Other IDs
- AOM 10093
- Acronym
- ANASILPRA
- Status last verified
- Aug 2016
- First submitted
- 25 Jan 2012
- Last updated
- 24 Aug 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01520467
- Acronym / sponsor ID
- ANASILPRA / P 100129
- Conditions
- Silver Russell Syndrome, Prader-Willi Syndrome
- Keywords
- SRS, PWS, pathological adrenarche, aromatase inhibitor, Children
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Apr 2012
- Primary completion
- Jul 2016 (actual)
- Study completion
- Oct 2016 (estimated)
- First posted
- 30 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anastrozole | Experimental | Drug: Anastrozolestratification according to the rare disease. Oral administration of Anastrozole (1mg/day) for 18 months |
| Placebo | Placebo comparator | Drug: Placebostratification according to the rare disease. Oral administration of 1 placebo tablet /day for 18 months |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnastrozoleAnastrozole (1mg/day), administered orally for 18 months | Drug | Anastrozole |
| Placebo1 placebo tablet /day administered orally for 18 months. | Drug | Placebo |
Primary outcome
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
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.
4 secondary outcomes
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
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
impact on the gonadotropic axis
Time frame: baseline, 6, 12 and 18 months
impact on the somatotropic axis (growth rate, IGF-1, IGFBP3).
Time frame: baseline, 6, 12 and 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Irène Netchine, MD, PhD principal investigator
Assistance Publique
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anastrozole in people with Silver Russell Syndrome and Prader-Willi Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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. (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2016.