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| Name | Class |
|---|---|
| Rett Syndrome Research Trust | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Copaxone | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glatiramer Acetate | Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and Final week of treatment (week 32) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and during final week of treatment (week 32) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Montefiore Medical center | The Bronx | New York | 10467 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27363291 | Result | 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. |
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All participants were recruited between Aug 2014-Jan 2015, from the population treated at the Rett Center at Montefiore.
Of 11 screened subjects, 10 met the inclusion/exclusion criteria and completed the trial. One patient was excluded due to prolonged QTc.
Data analysis was performed after the first 10 participants completed the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Copaxone | 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. Glatiramer Acetate |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All enrolled participants were female, ambulatory, and had been previously diagnosed with Rett syndrome.
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| ID | Title | Description |
|---|---|---|
| BG000 | Copaxone | 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. Glatiramer Acetate |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All 10 patients were females with genetically confirmed Rett syndrome. All were at least 10 years old and ambulatory (walking without assistance at the time of their enrollment). | Posted | Median | Inter-Quartile Range | cm/sec | Baseline and Final week of treatment (week 32) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Copaxone | 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. Glatiramer Acetate |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| laboratory result (elevated CPK) without clinical correlate, transitory | Musculoskeletal and connective tissue disorders | Systematic Assessment | not sympromatic |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Aleksandra Djukic | Montefiore Medical Center | 718 920 4378 | adjukic@montefiore.org |
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| ID | Term |
|---|---|
| D015518 | Rett Syndrome |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D000068717 | Glatiramer Acetate |
| ID | Term |
|---|---|
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| 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. | Baseline and Final week of treatment (week 32) |
| 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. | Baseline and Final week of treatment (week 32) |
| 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. | Baseline and Final week of treatment (week 32) |
| 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. | Baseline and Final week of treatment (week 32) |
| Participants |
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| Sex: Female, Male | All participants were female | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Units | Counts |
|---|---|
| Participants |
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| Secondary | 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. | One of the 10 enrolled patients experienced panic attack during the respiratory function testing so that session was discontinued. This left 9 participants for final analysis. | Posted | Median | Inter-Quartile Range | number of breath holds/hour | Baseline and during final week of treatment (week 32) |
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| Secondary | 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. | One of the 10 enrolled patients experienced panic attack during the respiratory function testing so that session was discontinued. This left 9 participants for final analysis. | Posted | Median | Inter-Quartile Range | percentage of time | Baseline and Final week of treatment (week 32) |
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| Secondary | 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. | Only 7 of the 10 recruited participants were able to complete the cognitive assessment. The remaining 3 participants could not be tested due to technical reasons. | Posted | Median | Inter-Quartile Range | percentage of time | Baseline and Final week of treatment (week 32) |
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| Secondary | 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. | Only 7 of the 10 recruited participants were able to complete the cognitive assessment. The remaining 3 participants could not be tested due to technical reasons. | Posted | Median | Inter-Quartile Range | number of fixations | Baseline and Final week of treatment (week 32) |
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| Secondary | 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. | Only 7 of the 10 recruited participants were able to complete the cognitive assessment. The remaining 3 participants could not be tested due to technical reasons. | Posted | Median | Inter-Quartile Range | seconds | Baseline and Final week of treatment (week 32) |
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| 0 |
| 10 |
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| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020271 | Heredodegenerative Disorders, Nervous System |