Clinical trial NCT02153723: Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
Official title: Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rett Syndrome
Keywords: Treatment trial, Rett syndrome, Glatiramer acetate
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: Rett Syndrome Research Trust
First posted: 2014-06-03
Enrollment: 10
Sex: FEMALE
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Gait Velocity as Measured by GAITRite System
timeFrame: Baseline and Final week of treatment (week 32)
Secondary outcomes:
measure: Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab)
timeFrame: Baseline and during final week of treatment (week 32)
measure: Breath Hold Time (Assessed in the Sleep Monitoring Lab)
timeFrame: Baseline and Final week of treatment (week 32)
measure: Visual Memory Novelty Score as Assessed by TX300 Tobii Computer.
timeFrame: Baseline and Final week of treatment (week 32)
measure: Visual Attention (Number of Fixations) Assessed by Eye-tracking TX300 Tobii Computer.
timeFrame: Baseline and Final week of treatment (week 32)
measure: Visual Attention (Fixation Length) Assessed by Eye-tracking TX300 Tobii Computer.
timeFrame: Baseline and Final week of treatment (week 32)
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical center
state: New York
Study officials:
References:
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.