Pharmacological Treatment of Rett Syndrome With Statins (Statins)

Pharmacological Treatment of Rett Syndrome With 3-Hydroxy-3 Methylglutaryl-coenzyme A Reductase Inhibitor-Lovastatin (Mevacor)

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

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: Lovastatin

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Females patients,
• Genetically confirmed RTT,
• Ambulatory.

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.

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
Experimental: Open label; 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.	Drug: Lovastatin; dose escallating; Other Names: Mevacor

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Memory Novelty Score as Assessed by TobiiTX 300 Eyetracking System	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.	final week of treatment, Week 32

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: Rett Syndrome Research Trust
• Investigators: Principal Investigator: Aleksandra Djukic, MD PhD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: July 20, 2015
• First Submitted That Met QC Criteria: September 28, 2015
• First Posted (Estimate): September 30, 2015

Study Record Updates

• Last Update Posted (Actual): July 12, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Lovastatin; Treatment trial
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; L 647318; Dihydromevinolin
• Other Study ID Numbers: 2014-4253

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO