Treatment with simvastatin of growth and bone abnormalities in children with Noonan syndrome

Treatment with HMG-COA reductase inhibitor (simvastatin) of growth and bone abnormalities in children with Noonan syndrome : a phase III randomised, double-blind, placebo-controlled therapeutic trial - RASTAT

Status

Not yet recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2016-000647-14-FR

Enrollment

Registered

2016-03-30

Start date

2016-05-23

Completion date

Unknown

Last updated

2018-09-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Noonan syndrome

Interventions

Trade Name: Simvastatin Product Name: Simvastatin Pharmaceutical Form: Film-coated tablet Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Genetically confirmed Noonan syndrome (mutations in PTPN11, SOS1, RAF1, KRAS, RIT1, SPRED, or SHOC2 genes) - Female child between 6 to 15 years, without menses, and with bone age = 13 years or male child between 6 to 16 years, and 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 - Participants with social security insurance or equivalent social protection. Are the trial subjects under 18? yes Number of subjects for this age range: 62 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: - Weight 1.5 upper limit of normal [ULN]), aspartate aminotransferase (> 1.5 ULN), or creatine phosphokinase (> 1.5 ULN) o Known hypersensitivity to simvastatin o Treatment with CYP3A4 inhibitors (erythromycin, clarithromycin, ketoconazole, itraconazole cyclosporine, or danazol), gemfibrozil - Growth promoting therapies such as recombinant human GH or IGF-1 treatment during the last 3 months

Design outcomes

Primary

Measure	Time frame
Main Objective: Evaluation of the effect of a 12 month simvastatin treatment on growth in Noonan syndrome children.;Secondary Objective: Evaluation of the effect of a 12-month simvastatin treatment on : - Other clinical (growth velocity, height, body mass index, waist circumference and hormonal (IGFBP-3) growth parameters - Growth plate and bone parameters - Cardiac function - Cognitive and behavioural deficits - Metabolism of lipids and carbohydrates - Study compliance - Adverse events;Primary end point(s): Change in serum levels of IGF-1 z-score during a 12-month treatment with simvastatin or placebo;Timepoint(s) of evaluation of this end point: Baseline and month 1,3,6 and 12	—

Measure

Time frame

Main Objective: Evaluation of the effect of a 12 month simvastatin treatment on growth in Noonan syndrome children.;Secondary Objective: Evaluation of the effect of a 12-month simvastatin treatment on : - Other clinical (growth velocity, height, body mass index, waist circumference and hormonal (IGFBP-3) growth parameters - Growth plate and bone parameters - Cardiac function - Cognitive and behavioural deficits - Metabolism of lipids and carbohydrates - Study compliance - Adverse events;Primary end point(s): Change in serum levels of IGF-1 z-score during a 12-month treatment with simvastatin or placebo;Timepoint(s) of evaluation of this end point: Baseline and month 1,3,6 and 12

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Secondary

Measure	Time frame
Secondary end point(s): Growth parameters : - Height, weight, body mass index and waist circumference - Serum IGFBP-3 levels Growth plates and bone parameters : - Serum C-type natriuretic peptide and amino-terminal propeptide of C-type natriuretic peptide (growth plate markers) - Serum levels of bone alkaline phosphatase (Bone formation parameters) and carboxy-terminal crosslinks (bone resorption parameters) - Bone mineral content, areal and volumetric bone mineral density of the whole body without the head and of the lumbar spine Cardiac function (echocardiography) - Left ventricular maximal wall thickness - Left ventricular diastolic function using mitral flow and pulsed Tissue Doppler to record the Ea, Aa, Ea/Aa and E/Ea ratios) Cognitive and behavioural deficits - Attention problems and internalising behavioural problems Metabolism of lipids and carbohydrates - Lipids levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) - Serum levels of leptins and adipokines - Fat body mass measured by DXA - Insulin sensitivity indices based on fasting plasma insulin and glucose levels (HOMA and QUICKI) Study compliance - Analysis of questionnaires - Accounting for capsules Adverse events - Muscular symptoms (myalgia, myopathy, or rhabdomyolysis) - Increased CK levels - Increased levels of alanine aminotransferase and aspartate aminotransferase;Timepoint(s) of evaluation of this end point: - Clinical examination parameters (height, weight, body mass index, waist circumference and blood pressure) : Baseline et months 1,3,6,9 et 12. - Cognitive and behavioural deficits : Baseline and month 12 - Tolerance biological parameters (metabolism of lipids and carbohydrates, ALT, AST and CK) : Baseline and months 1,3,6,9 and 12 - Efficacy biological parameters (IGFBP-3, bone alkaline phosphatase, CTX, glycemia, insulinemia, leptin) : Baseline and months 3,6 and 12 - Bone age, body co	—

Measure

Time frame

Secondary end point(s): Growth parameters : - Height, weight, body mass index and waist circumference - Serum IGFBP-3 levels Growth plates and bone parameters : - Serum C-type natriuretic peptide and amino-terminal propeptide of C-type natriuretic peptide (growth plate markers) - Serum levels of bone alkaline phosphatase (Bone formation parameters) and carboxy-terminal crosslinks (bone resorption parameters) - Bone mineral content, areal and volumetric bone mineral density of the whole body without the head and of the lumbar spine Cardiac function (echocardiography) - Left ventricular maximal wall thickness - Left ventricular diastolic function using mitral flow and pulsed Tissue Doppler to record the Ea, Aa, Ea/Aa and E/Ea ratios) Cognitive and behavioural deficits - Attention problems and internalising behavioural problems Metabolism of lipids and carbohydrates - Lipids levels (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides) - Serum levels of leptins and adipokines - Fat body mass measured by DXA - Insulin sensitivity indices based on fasting plasma insulin and glucose levels (HOMA and QUICKI) Study compliance - Analysis of questionnaires - Accounting for capsules Adverse events - Muscular symptoms (myalgia, myopathy, or rhabdomyolysis) - Increased CK levels - Increased levels of alanine aminotransferase and aspartate aminotransferase;Timepoint(s) of evaluation of this end point: - Clinical examination parameters (height, weight, body mass index, waist circumference and blood pressure) : Baseline et months 1,3,6,9 et 12. - Cognitive and behavioural deficits : Baseline and month 12 - Tolerance biological parameters (metabolism of lipids and carbohydrates, ALT, AST and CK) : Baseline and months 1,3,6,9 and 12 - Efficacy biological parameters (IGFBP-3, bone alkaline phosphatase, CTX, glycemia, insulinemia, leptin) : Baseline and months 3,6 and 12 - Bone age, body co

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Countries

France

Contacts

Public ContactCaroline Peyrot

University Hospital Toulouse

peyrot.c@chu-toulouse.fr+3305 61 77 84 86

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026