Treatment With HMG-COA Reductase Inhibitor of Growth and Bone Abnormalities in Children With Noonan Syndrome

NCT02713945 | Completed Phase 3 DMC

• 1 other identifier: RC31/15/7826
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 12

Brief Summary

This study evaluate the efficacy of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase inhibitors, also known as "statins" in the treatment of growth and skeletal abnormalities in children with Noonan syndrome. Half of patients will receive simvastatin while the other half will receive a placebo.

Conditions

Noonan Syndrome

Keywords

Simvastatin; Ras; MAPK

Outcome Measures

Primary Outcomes (1)

• Effect of a 12-month simvastatin treatment on growth in NS children as assessed by change in Insulin-like Growth Factor-1 (IGF-1) levels converted to age and sex specific z-scores

  Baseline, month 1, month 3, month 6, month 9 and month 12

Secondary Outcomes (17)

• Effect of a 12-month simvastatin treatment on growth velocity as assessed by Height measurement.

  Baseline, month 1, month 3, month 6, month 9 and month 12

• Effect of a 12-month simvastatin treatment on body mass index as assessed by height and weight measurement.

  Baseline, month 1, month 3, month 6, month 9 and month 12

• Effect of a 12-month simvastatin treatment on waist circumference as assessed by clinical examination

  Baseline, month 1, month 3, month 6, month 9 and month 12

• Effect of a 12-month simvastatin treatment on hormonal growth parameters as assessed by serum IGFBP-3 levels

  Baseline, month 1, month 3, month 6, month 9 and month 12

• Effect of a 12-month simvastatin treatment on growth plates as assessed by serum C-type natriuretic peptide (CNP) levels

  Baseline, month 1, month 3, month 6, month 9 and month 12

Study Arms (2)

Simvastatin

EXPERIMENTAL

Simvastatin administrated orally at 10 mg once a day in the morning during the first month Simvastatin administrated orally at 20 mg once a day in the morning during the second month During months 3 to 12, the dose will be fixed at 20 mg per day for children aged 12 years and younger and 40 mg for adolescent older than 12 years.

Drug: Simvastatin

Control

PLACEBO COMPARATOR

Placebo administrated orally once daily in the morning

Drug: Placebo

Interventions

Simvastatin DRUG

Experimental drug administrated orally

Simvastatin

Placebo DRUG

Treatment for the control group

Control

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Genetically confirmed Noonan syndrome
• Female child between 6 to 15 years, without menses, with bone age \< 13 years
• Male child between 6 to 16 years, with bone age \< 14 years
• Decreased growth velocity (\< -1 SDS) and/or short stature (height \< -2 SDS or -1,5 SDS under target height)
• Informed consent obtained from child and parents

You may not qualify if:

• Contraindication to simvastatin treatment :
• Progressive liver disease, increased serum levels of alanine aminotransferase (ALT) (\> 1,5 uper limit of normal (ULN)), aspartate aminotransferase (\> 1,5 ULN)
• Known hypersensitivity to simvastatin
• Pregnancy
• Treatment with CYP3A4 inhibitors (erythromycin, clarithromycin, ketoconazole, or itraconazole)
• Growth promoting therapies such as recombinant human Growth Hormone (GH) or IGF-1 treatment

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (12)

CHU Angers Unité d'endocrinologie pédiatrique

Angers, France

Location

CHU Bordeaux Unité de Génétique pédiatrique

Bordeaux, France

Location

Chu Dijon

Dijon, France

Location

CHRU Lille Unité d'endocrinologie pédiatrique

Lille, France

Location

CHU Lyon Unité d'endocrinologie pédiatrique

Lyon, France

Location

CHU Marseille La Timone Unité d'Endocrinologie pédiatrique

Marseille, France

Location

Chu Montpellier

Montpellier, France

Location

CHU Nancy Unité de Génétique pédiatrique

Nancy, France

Location

Hôpital Robert Debré Unité de Génétique pédiatrique

Paris, France

Location

Hôpital Trousseau Unité d'endocrinologie pédiatrique

Paris, France

Location

CHU Rennes Unité de Génétique pédiatrique

Rennes, France

Location

CHU Toulouse Hôpital des Enfants

Toulouse, France

Location

MeSH Terms

Conditions

Noonan Syndrome

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Thomas Edouard, MD, PHD

  Children's Hospital, Toulouse University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2016
• First Posted: March 21, 2016
• Study Start: January 25, 2017
• Primary Completion: March 3, 2023
• Study Completion: March 3, 2023
• Last Updated: May 11, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (12)