Pharmacological Treatment of Rett Syndrome With Statins

Phase 2

Completed

Brief Summary: This is a phase 2 , open label, dose escalating study of Lovastatin in Rett syndrome.

Detailed Description: Excess neuronal cholesterol plays a role in the pathophysiology of Rett syndrome(RTT) and the investigators hypothesise that inhibition of cholesterol synthesis in the CNS will reduce neuronal cholesterol and lead to improvement in Rett syndrome related symptoms.

Goal: To determine the optimal dosing regiment of Lovastatin for patients with RTT and to identify the most appropriate primary outcome measure for the subsequent Phase 3 study.

Phase 2, dose escalation study.

Primary outcome: Gait speed Secondary outcomes: respiratory function, cognition, EEG (encephalopathy), Rett syndrome severity scale, neurodevelopmental assessment (QOL)

20 ambulatory female patients with genetically confirmed.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Presence of co morbid non-Rett related disease,
History of adverse reaction/hypersensitivity to statins,
Levels of aspartate-amino trans-ferase (AST), alanine-amino transferase (ALT) or creatine kinase (CK) triple the normal values,
Active liver disease,
Concomitant use of strong CYP3A4 inhibitors,
Condition predis-posing to renal failure secondary to rhabdomyolysis (scoliosis surgery within 6 months),
Oral contraceptives use.

Arm && Interventions

Group	Intervention	Description
Open label	Lovastatin	Treatment with Lovastatin, dose escalating trial according to the following schedule: 10 mg daily for 8 week 20 mg daily for 8 weeks 40 mg daily for 16 weeks.

Primary Outcome Measures

Name	Time	Method
Gait Velocity as Measured by GAITRite System	During final week of treatment, week 32	To perform quantitative gait assessment using a computerized walkway with embedded pressure sendors (GAIT rite)

Secondary Outcome Measures

Name	Time	Method
Visual Memory Novelty Score as Assessed by TobiiTX 300 Eyetracking System	final week of treatment, Week 32	Novelty score is considered a composite measure of visual memory.Test is a standardized neuropsychological test( "Rose test") adapted for eye tracking system. The present study made use of a well-established battery of "visual paired comparison" problems .There were nine problems: five using achromatic photos of faces and four using multicolored abstract patterns paired stimuli , separated by 23°. For each problem, two identical stimuli are briefly presented side by side for familiarization, then the familiar and a new one are paired on test Recognition(memory) is indexed by a novelty score (percentage of looking to the novel target on test). Higher novelty scores were related to better recognition (index of better memory) Scores range from 0.0-1.0 (0-100%) and indicate 1) more overall looking at novel target and (2) more fixations to novel targets. Score of .5 (50%) indicates looking "by change" only with no recognition.