Treatment of the Hutchinson-Gilford Progeria Syndrome With a Combination of Pravastatin and Zoledronic Acid

Study Overview
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Brief Summary
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We suggest treating the Hutchinson-Gilford Progeria Syndrome by two molecules (zoledronic acid and pravastatin).The therapeutic approach which we propose has for objectives to reduce, to prevent or to delay the gravest infringements of the disease, to prolong the life of the children, and in a more general way, aim at improving their living conditions.

Official Title
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Treatment of the Hutchinson-Gilford Progeria Syndrome With a Combination of Pravastatin and Zoledronic Acid

Conditions
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Hutchinson-Gilford Progeria Syndrome

Intervention / Treatment
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* Drug: Zoledronic acid, pravastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Molecularly characterised patients with a known mutation of their LMNA gene leading to the production of a farnesylated prelamin A, whether truncated or not Patients must be able to travel and consult in Marseille, France for necessary explorations planned at the inclusion step, then following the protocol flow chart for zoledronic acid injections and follow-up visits Patient older than 3 years Patients affiliated or beneficiary of a legal medical insurance Adult patients certifying they have been properly informed about the protocol, and they signed a written consent form. Children and/or disabled patients whose parents/legal tutor have been informed and have signed a written consent form Exclusion Criteria: Known hypersensitivity to pravastatin or zoledronic acid Seric transaminase levels higher than 3 times of normal value CPK level higher than 5 times of normal value Creatininemia higher than 0.5mg/dl or 44mM, or creatinin clearance lower than 70ml/min/1.73m3 Presence of dental troubles, or recent dental trouble Maxillary osteonecrosis or bone nakedness antecedent Congenital galacosemia, glucose or galactose maladsorption syndrome, lactase deficiency Every other pathology thought to be incompatible with proposed treatment by the investigator Under treatment that can interfere with pravastatin and/or zoledronate metabolisms

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>Zoledronic acid, pravastatin | Drug: Zoledronic acid, pravastatin<br>* Pravastatin : 10 mg daily Zoledronic acid : slow (30 mn) intravenous injections, diluted into 50 ml of saline solution following this schedule : injection 1, S1: 0.0125 mg/kg of zoledronic acid injection 2, S6: 0.025 mg/kg of zoledronic acid injection 3, S12 and following, trimestrial basis, 0.05 mg/kg of zoledronic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the tolerance and efficacy of pravastatin and zoledronic acid in combination on the patient's weight, height and bone metabolism in Progeria treatment |  | 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the tolerance and efficacy of the treatment on other clinical and biological symptoms |  | 48 months |