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

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.

Study Overview

• Status: Completed
• Conditions: Hutchinson-Gilford Progeria Syndrome
• Intervention / Treatment: Drug: Zoledronic acid, pravastatin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13385
    • Laboratoire de Génétique Moléculaire - Hopital de la Timone

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: 1; Zoledronic acid, pravastatin	Drug: Zoledronic acid, pravastatin; 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille
• Investigators: Principal Investigator: Nicolas LEVY, MD, Assistance Publique Des Hopitaux de Marseille

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): July 1, 2013

Study Registration Dates

• First Submitted: August 1, 2008
• First Submitted That Met QC Criteria: August 5, 2008
• First Posted (ESTIMATE): August 8, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): July 8, 2013
• Last Update Submitted That Met QC Criteria: July 4, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Laminopathies; Syndrome; Progeria; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Bone Density Conservation Agents; Pravastatin; Zoledronic Acid
• Other Study ID Numbers: 2008-002471-27; 2008-15 (SSWAHS)