Brief Title
Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
Official Title
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Gait Velocity as Measured by GAITRite System
Secondary Outcome
Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab)
Condition
Rett Syndrome
Intervention
Glatiramer Acetate
Study Arms / Comparison Groups
Copaxone
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
10
Start Date
August 2013
Completion Date
January 2016
Primary Completion Date
August 2014
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
Gender
Female
Ages
10 Years - N/A
Accepts Healthy Volunteers
No
Contacts
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Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02153723
Organization ID
13-05-117
Responsible Party
Principal Investigator
Study Sponsor
Montefiore Medical Center
Collaborators
Rett Syndrome Research Trust
Study Sponsor
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Verification Date
October 2018