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Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)

Primary Purpose

Rett Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Glatiramer Acetate
Sponsored by
Montefiore Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rett Syndrome focused on measuring Treatment trial, Rett syndrome, Glatiramer acetate

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Female patients with genetically confirmed Rett Syndrome (RTT)
  • Age: 10 or more years old. Selection of the age is based on the available evidence of the safety of Glatiramer Acetate (GA) in this group, and the relative homogeneity/stability of the phenotype, which is not expected to spontaneously change within a 6 month period at this age
  • Ambulatory (with our without support)

Exclusion Criteria:

  • Prolonged Qtc (obtained within 30 days prior to enrollment)
  • Presence of co morbid non-Rett related disease
  • Presence of immunodeficiency requiring intravenous immunoglobulin 3 (IVIG 3) months prior to enrollment
  • Allergy/sensitivity to GA or mannitol
  • Inability or unwillingness of legal guardians to give written informed consent

Sites / Locations

  • Montefiore Medical center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Copaxone

Arm Description

Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection.

Outcomes

Primary Outcome Measures

Gait Velocity as Measured by GAITRite System
To perform quantitative gait assessments a computerized walkway (457 × 90.2 × 0.64cm) with embedded pressure sensors (GAIT Rite system) was used. Subjects walked on the walkway for two trials, while wearing comfortable footwear.

Secondary Outcome Measures

Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab)
Breath hold index is defined as number of breath holds/hour. Respirations were monitored with sleep monitoring equipment during the daytime at the polysomnography laboratory with additional oronasal airflow, electromyography (EMG), EEG and video monitoring to confirm wakefulness during the period of study.
Breath Hold Time (Assessed in the Sleep Monitoring Lab)
Breath Hold Time is defined as percentage of time spent holding the breath in a specific time unit. It is measured by a standard medical technique where belts are placed on the chest and abdomen to record movement and sensors are used to record nasal flow. Wake respiration was monitored with sleep monitoring equipment during the daytime at the polysomnography laboratory with additional oronasal airflow, EMG, EEG and video monitoring to confirm wakefulness during the period of study.
Visual Memory Novelty Score as Assessed by TX300 Tobii Computer.
Eye-tracking is considered an indication of visual memory. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 computer (Tobii Technology, Danderyd, Sweden). The actual data given by the computer represents the percentage of time spent looking at a novel visual target - this is called the novelty score. Visual memory, as indexed by the novelty score, is the percentage of time spent looking at a novel target during the test ("visual paired comparison paradigm"). Duration of testing was 2 minutes.
Visual Attention (Number of Fixations) Assessed by Eye-tracking TX300 Tobii Computer.
Visual attention is indexed by duration and number of fixations on novel target on testing. The standard method of assessing visual attention in neuropsychology is by measuring: A)number of fixations (how many times the subject looks at each of the 2 visual targets). The higher number of fixations, the more attentive the subject to that visual target. B) duration of fixations in seconds (the longer the fixation the more attentive). Duration of fixations correlates with intelligence: the smarter the person is the shorter his fixations are. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 (Tobii Technology AB, Danderyd, Sweden). The measured index is called the Novelty Score which indicates the percentage of time spent looking at novel visual target. Duration of testing session was 2 minutes.
Visual Attention (Fixation Length) Assessed by Eye-tracking TX300 Tobii Computer.
The standard method of assessing visual attention in neuropsychology is by measuring: A)number of fixations (how many times the subject looks at each of the 2 visual targets). The higher number of fixations, the more attentive the subject to that visual target. B) duration of fixations in seconds (the longer the fixation the more attentive). Duration of fixations correlates with intelligence: the smarter the person is the shorter his fixations are. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 (Tobii Technology AB, Danderyd, Sweden). The measured index is called the Novelty Score which indicates the percentage of time spent looking at novel visual target. Visual attention is indexed by number of fixations on novel target on test. Duration of testing session was 2 minutes.

Full Information

First Posted
May 26, 2014
Last Updated
October 4, 2018
Sponsor
Montefiore Medical Center
Collaborators
Rett Syndrome Research Trust
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1. Study Identification

Unique Protocol Identification Number
NCT02153723
Brief Title
Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
Official Title
Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
January 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Montefiore Medical Center
Collaborators
Rett Syndrome Research Trust

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
A phase 2 open label trial to test a potential drug treatment for Rett syndrome, the leading known genetic cause of severe neurological impairment in girls. The drug, Copaxone (generic name - Glatiramer acetate) is medication FDA approved for the treatment of multiple sclerosis. Copaxone's high safety profile has been documented in large cohorts of patients for more than 12 years.
Detailed Description
Background/rationale for the study: In Rett syndrome brain cells aren't actually lost, instead poor maturation of connections between brain cells (synapses) prevents effective neurological functioning, and is the main morphological feature of the disease. The MeCP2 gene plays a major role in transcriptional regulation of other genes, one of which is the gene encoding brain-derived neurotrophic factor (BDNF). The disease progression and severity of symptoms is directly affected by the level of BDNF expression. An increase of BDNF levels (by genetic manipulations or pharmacological agents) leads to delayed onset of Rett syndrome-like symptoms in experimental models; rescued gait/mobility, improved quality of life and increased survival rates. Copaxone treatment by subcutaneous injection caused elevation of BDNF levels. Quantitative immunofluorescence assays showed about a twofold increase in neuronal expression of BDNF following Copaxone treatment. We expect that an increase in BDNF levels with Copaxone administration will stimulate communication between brain cells (synaptic maturation), which will lead to amelioration of symptoms (motor functions/gait, cognitive functions, breathing, encephalopathy and improve quality of life) for girls with Rett syndrome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rett Syndrome
Keywords
Treatment trial, Rett syndrome, Glatiramer acetate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Copaxone
Arm Type
Experimental
Arm Description
Dose escalation: Study drug will be administered once a week for 4 weeks, twice a week for 4 weeks and daily for 24 weeks. Drug is administered as a subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Glatiramer Acetate
Other Intervention Name(s)
Copaxone
Primary Outcome Measure Information:
Title
Gait Velocity as Measured by GAITRite System
Description
To perform quantitative gait assessments a computerized walkway (457 × 90.2 × 0.64cm) with embedded pressure sensors (GAIT Rite system) was used. Subjects walked on the walkway for two trials, while wearing comfortable footwear.
Time Frame
Baseline and Final week of treatment (week 32)
Secondary Outcome Measure Information:
Title
Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab)
Description
Breath hold index is defined as number of breath holds/hour. Respirations were monitored with sleep monitoring equipment during the daytime at the polysomnography laboratory with additional oronasal airflow, electromyography (EMG), EEG and video monitoring to confirm wakefulness during the period of study.
Time Frame
Baseline and during final week of treatment (week 32)
Title
Breath Hold Time (Assessed in the Sleep Monitoring Lab)
Description
Breath Hold Time is defined as percentage of time spent holding the breath in a specific time unit. It is measured by a standard medical technique where belts are placed on the chest and abdomen to record movement and sensors are used to record nasal flow. Wake respiration was monitored with sleep monitoring equipment during the daytime at the polysomnography laboratory with additional oronasal airflow, EMG, EEG and video monitoring to confirm wakefulness during the period of study.
Time Frame
Baseline and Final week of treatment (week 32)
Title
Visual Memory Novelty Score as Assessed by TX300 Tobii Computer.
Description
Eye-tracking is considered an indication of visual memory. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 computer (Tobii Technology, Danderyd, Sweden). The actual data given by the computer represents the percentage of time spent looking at a novel visual target - this is called the novelty score. Visual memory, as indexed by the novelty score, is the percentage of time spent looking at a novel target during the test ("visual paired comparison paradigm"). Duration of testing was 2 minutes.
Time Frame
Baseline and Final week of treatment (week 32)
Title
Visual Attention (Number of Fixations) Assessed by Eye-tracking TX300 Tobii Computer.
Description
Visual attention is indexed by duration and number of fixations on novel target on testing. The standard method of assessing visual attention in neuropsychology is by measuring: A)number of fixations (how many times the subject looks at each of the 2 visual targets). The higher number of fixations, the more attentive the subject to that visual target. B) duration of fixations in seconds (the longer the fixation the more attentive). Duration of fixations correlates with intelligence: the smarter the person is the shorter his fixations are. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 (Tobii Technology AB, Danderyd, Sweden). The measured index is called the Novelty Score which indicates the percentage of time spent looking at novel visual target. Duration of testing session was 2 minutes.
Time Frame
Baseline and Final week of treatment (week 32)
Title
Visual Attention (Fixation Length) Assessed by Eye-tracking TX300 Tobii Computer.
Description
The standard method of assessing visual attention in neuropsychology is by measuring: A)number of fixations (how many times the subject looks at each of the 2 visual targets). The higher number of fixations, the more attentive the subject to that visual target. B) duration of fixations in seconds (the longer the fixation the more attentive). Duration of fixations correlates with intelligence: the smarter the person is the shorter his fixations are. Eye-tracking data was recorded at 300 Hz sampling rate using a Tobii T300 (Tobii Technology AB, Danderyd, Sweden). The measured index is called the Novelty Score which indicates the percentage of time spent looking at novel visual target. Visual attention is indexed by number of fixations on novel target on test. Duration of testing session was 2 minutes.
Time Frame
Baseline and Final week of treatment (week 32)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female patients with genetically confirmed Rett Syndrome (RTT) Age: 10 or more years old. Selection of the age is based on the available evidence of the safety of Glatiramer Acetate (GA) in this group, and the relative homogeneity/stability of the phenotype, which is not expected to spontaneously change within a 6 month period at this age Ambulatory (with our without support) Exclusion Criteria: Prolonged Qtc (obtained within 30 days prior to enrollment) Presence of co morbid non-Rett related disease Presence of immunodeficiency requiring intravenous immunoglobulin 3 (IVIG 3) months prior to enrollment Allergy/sensitivity to GA or mannitol Inability or unwillingness of legal guardians to give written informed consent
Facility Information:
Facility Name
Montefiore Medical center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27363291
Citation
Djukic A, Holtzer R, Shinnar S, Muzumdar H, Rose SA, Mowrey W, Galanopoulou AS, Shinnar R, Jankowski JJ, Feldman JF, Pillai S, Moshe SL. Pharmacologic Treatment of Rett Syndrome With Glatiramer Acetate. Pediatr Neurol. 2016 Aug;61:51-7. doi: 10.1016/j.pediatrneurol.2016.05.010. Epub 2016 May 27.
Results Reference
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Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)

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