Rett Syndrome
Conditions
Keywords
Treatment trial, Lovastatin
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.
Interventions
DRUGLovastatin
dose escallating
Sponsors
Rett Syndrome Research Trust
Montefiore Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
3 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Female patients with genetically confirmed RTT, treatment arm only.
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.
Lovastatin: dose escallating | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Open Label |
|---|---|
| Age, Categorical <=18 years | 20 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Gait Velocity as Measured by GAITRite System
To perform quantitative gait assessment using a computerized walkway with embedded pressure sendors (GAIT rite)
Time frame: During final week of treatment, week 32
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label | Gait Velocity as Measured by GAITRite System | 58.6 cm/sec |
Secondary
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.
Time frame: final week of treatment, Week 32
Population: Calculation done on intent-to-treat population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Open Label | Visual Memory Novelty Score as Assessed by TobiiTX 300 Eyetracking System | Pre-treatment | 44.85 percent |
| Open Label | Visual Memory Novelty Score as Assessed by TobiiTX 300 Eyetracking System | Post treatment | 58.93 percent |