Rett SyndromePhase 2NCT02153723
Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
A Phase 2 study testing Glatiramer Acetate in people with Rett Syndrome, run by Montefiore Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 10 years and older, women only
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- Glatiramer Acetate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to Jan 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Montefiore Medical center
The Bronx, New York, 10467
About this study
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.
Read the 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.
- Conditions
- Rett Syndrome
- Being tested
- Glatiramer Acetate
- Keywords
- Treatment trial, Rett syndrome, Glatiramer acetate
- Medical subject headings
- Rett Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glatiramer AcetateDrug
Also called Copaxone
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Glatiramer Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Final week of treatment (week 32)
Secondary outcomes (5)
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.
Measured: Baseline and during final week of treatment (week 32)
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.
Measured: 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.
Measured: 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.
- 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.
Measured: 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.
- 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.
Measured: Baseline and Final week of treatment (week 32)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2014 (estimated)
- Study startAug 2013
- Primary completionAug 2014
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Rett Syndrome Research Trust
- Responsible party
- Principal investigator, Aleksandra Djukic, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02153723
- Sponsor's protocol ID
- 13-05-117
- Status last verified
- Oct 2018
- First submitted
- 26 May 2014
- Last updated
- 5 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 27363291
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
- ClinicalTrials.gov ID
- NCT02153723
- Acronym / sponsor ID
- 13-05-117
- Conditions
- Rett Syndrome
- Keywords
- Treatment trial, Rett syndrome, Glatiramer acetate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Collaborators
- Rett Syndrome Research Trust
- Study start
- Aug 2013
- Primary completion
- Aug 2014 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 3 Jun 2014 (estimated)
- Results
- Posted 5 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Copaxone | Experimental | Drug: Glatiramer AcetateDose 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. |
Who may qualify
- Ages
- 10 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glatiramer AcetateAlso: Copaxone | Drug | Copaxone |
Primary outcome
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.
5 secondary outcomes
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 Time (Assessed in the Sleep Monitoring Lab)
Time frame: Baseline and Final week of treatment (week 32)
Visual Memory Novelty Score as Assessed by TX300 Tobii Computer.
Time frame: Baseline and Final week of treatment (week 32)
Visual Attention (Number of Fixations) Assessed by Eye-tracking TX300 Tobii Computer.
Time frame: Baseline and Final week of treatment (week 32)
Visual Attention (Fixation Length) Assessed by Eye-tracking TX300 Tobii Computer.
Time frame: Baseline and Final week of treatment (week 32)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27363291Djukic 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Glatiramer Acetate in people with Rett Syndrome, run by Montefiore Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gait Velocity as Measured by GAITRite System (time frame: Baseline and Final week of treatment (week 32)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02153723, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2018.