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Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)

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ClinicalTrials.gov Identifier: NCT02153723
Recruitment Status : Completed
First Posted : June 3, 2014
Results First Posted : November 5, 2018
Last Update Posted : November 5, 2018
Sponsor:
Collaborator:
Rett Syndrome Research Trust
Information provided by (Responsible Party):
Aleksandra Djukic, Montefiore Medical Center

Tracking Information
First Submitted Date  ICMJE May 26, 2014
First Posted Date  ICMJE June 3, 2014
Results First Submitted Date  ICMJE July 20, 2015
Results First Posted Date  ICMJE November 5, 2018
Last Update Posted Date November 5, 2018
Study Start Date  ICMJE August 2013
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2018)
Gait Velocity as Measured by GAITRite System [ Time Frame: Baseline and Final week of treatment (week 32) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2014)
Gait speed [ Time Frame: 32 weeks ]
To perform quantitative gait assessments a computerized walkway (457 × 90.2 × 0.64cm) with embedded pressure sensors (GAIT Rite system) will be used. Subjects will be asked to walk on the walkway for two trials wearing comfortable footwear.
Change History Complete list of historical versions of study NCT02153723 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2018)
  • Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab) [ Time Frame: Baseline and during final week of treatment (week 32) ]
    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) [ Time Frame: Baseline and Final week of treatment (week 32) ]
    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. [ Time Frame: Baseline and Final week of treatment (week 32) ]
    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. [ Time Frame: Baseline and Final week of treatment (week 32) ]
    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. [ Time Frame: Baseline and Final week of treatment (week 32) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2014)
autonomic (respiratory) function [ Time Frame: 32 weeks ]
Wake respirations using the NOX 3 . During one of the three days of monitoring, we will also monitor the same parameters 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 29, 2014)
  • visual attention, memory and visual pursuit [ Time Frame: 32 weeks ]
    Eye-tracking data will be recorded at 300 Hz sampling rate using a Tobii T300 (Tobii Technology AB, Danderyd, Sweden).
  • EEG [ Time Frame: 32 weeks ]
    routine EEG
  • Quality of life [ Time Frame: 32 weeks ]
    The Child Health Questionnaire- Parent Report (CHQ-PF50) The CHQ-PF50 includes broad-spectrum areas, which can be divided in-to 12 domains: Physical Functioning, Role/Social Limitations-Emotional/Behavioral, Role/Social Limitations-Physical, Behav-ior, Mental Health, Self-Esteem, General Health, Bodily Pain, Family Activities, Parent Impact-Time, Parent Impact-Emotional, and Family Cohesion.
 
Descriptive Information
Brief Title  ICMJE Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
Official Title  ICMJE Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rett Syndrome
Intervention  ICMJE Drug: Glatiramer Acetate
Other Name: Copaxone
Study Arms  ICMJE Experimental: 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.

Intervention: Drug: Glatiramer Acetate
Publications * Djukic A, Holtzer R, Shinnar S, Muzumdar H, Rose SA, Mowrey W, Galanopoulou AS, Shinnar R, Jankowski JJ, Feldman JF, Pillai S, Moshé 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 4, 2018)
10
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2014)
20
Actual Study Completion Date  ICMJE January 2016
Actual Primary Completion Date August 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 10 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02153723
Other Study ID Numbers  ICMJE 13-05-117
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Aleksandra Djukic, Montefiore Medical Center
Study Sponsor  ICMJE Montefiore Medical Center
Collaborators  ICMJE Rett Syndrome Research Trust
Investigators  ICMJE Not Provided
PRS Account Montefiore Medical Center
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP