An Open Label, Exploratory Study to Investigate the Treatment Effect of Glatiramer Acetate on Girls Woth Rett Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Sheba Medical Center
Sponsor:
Information provided by (Responsible Party):
Prof. Bruria Ben-Zeev MD, Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT02023424
First received: December 23, 2013
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

Primary Objective: To test the hypothesis that 6 months treatment with glatiramer acetate (GA) decreases epileptiform activity in young girls with Rett syndrome.

Primary Safety Objective:To evaluate the safety and tolerability of 6 months treatment with GA in these patients.

Secondary Objectives:

  1. To test the hypothesis that 6 months treatment with glatiramer acetate (GA) improves respiratory dysfunction.
  2. To evaluate the effect of GA treatment on general behaviour communication, hand stereotyping, feeding, sleep and other autonomic symptoms: gastrointestinal and cardiac.
  3. To assess the effect of GA treatment on bodily development.

Primary Endpoint:Improvement of epileptiform activity as recorded in a 24-hours EEG.

Primary Safety Endpoint:Frequency and severity of treatment-related AEs (including safety lab parameters).

Secondary Endpoints:

  1. Improvement in the scoring of breath holds and hyperventilation, as measured with non-invasive respiratory inductance plethysmography (NoxT3 device) and parents' diaries.
  2. Changes in general behaviour, communication, feeding and motor skills as assessed by the investigator (based on Kerr and Naidu validated severity scores) and recorded in parents' diary.
  3. Decrease in seizure frequency as reported in parents' diary.
  4. Improvement in sleep schedule as recorded in a sleep diary.
  5. Change in height and weight. Population:Ten girls, 6 to 15 years old, diagnosed with Rett syndrome (RTT) Study Design:This is a single - center, exploratory, open-label, study in 10 girls diagnosed with RTT. The study will consist of four parts: Screening and baseline assessments, initial and final dose-setting period, treatment period and end-of study follow-up.

Investigational Product:Glatiramer Acetate (Copaxone® , Teva Pharmaceutical Industries Ltd.) Sample Size Consideration: The planned sample size of 10 patients was considered adequate by the investigator for this phase I exploratory proof-of-concept study. The study is not expected to show statistical significance or statistical power, only a trend for the study endpoints. Each patient will serve as her own control.

Duration of Study: Approximately 8 months per patient (including up to 2 weeks pre-treatment assessment, 6 months initial dose and treatment periods and end-of study visit).

Overall study duration: the study is expected to be completed within 12 months (dependent on rate of recruitment).


Condition Intervention Phase
Rett Syndrome
Drug: Glatiramer Acetate (Copaxone®)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Exploratory Study to Investigate the Treatment Effect og Glatiramer Acetate (Copaxone ®) on Girls Woth Rett Syndrome

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Improvement of epileptiform activity as recorded in a 24-hours EEG. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1.Improvement in the scoring of breath holds and hyperventilation, as measured with non-invasive respiratory inductance plethysmography (NoxT3 device) and parents' diaries. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • 2. Changes in general behaviour, communication, feeding and motor skills as assessed by the investigator (based on Kerr and Naidu validated severity scores) and recorded in parents' diary. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Decrease in seizure frequency as reported in parents' diary. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Improvement in sleep schedule as recorded in a sleep diary. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
  • Change in height and weight [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: January 2014
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Copaxone
Glatiramer Acetate (Copaxone® , Teva Pharmaceutical Industries Ltd.) 20 mg daily or in an interval determined in the Dose Setting period. Administration will be subcutaneous to various areas on the body: back of the upper arms (2 areas), front and outside of thighs (2 areas), upper buttocks/rear hips (2 areas), and stomach (the abdomen).
Drug: Glatiramer Acetate (Copaxone®)
GA is a potent inducer of Th2-cells and modulates these immune cells to secrete high levels of neurotrophic factors, particularly BDNF. The induced cells cross the blood brain barrier (BBB), accumulate in the CNS and express BDNF and other regulatory substances in situ.

Detailed Description:

...

  Eligibility

Ages Eligible for Study:   6 Years to 15 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Females, age 6-15 years (inclusive).
  2. Patients whose parents or legal custodians have provided written informed consent to participate in the study.
  3. A diagnosis of RTT (classical or variant), defined according to the internationally agreed 2010 RetSearch criteria [4].
  4. Evidence of a genetically defined pathological change in the MECP2 gene (point mutation or deletion)
  5. Patients with known epileptiform activity as recorded on EEG.
  6. Blood pressure and heart rate within normal limits (blood pressure: systolic 90-140 mmHg; diastolic 50-90 mmHg, heart rate 40-120 beats per minute
  7. An electrocardiogram (ECG) which, according to the Investigator's judgment does not contraindicate participation in the study.
  8. No clinically significant abnormalities in haematology, blood chemistry lab tests at screening.
  9. Parents must be able to understand the requirements of the study and must be willing to comply with the requirements of the study

Exclusion Criteria:

  1. Any medical problem or chronic illness beyond those known to be associated with Rett Syndrome which, in the investigator's judgment, contraindicates administration of the study medication.
  2. Severe respiratory dysfunction (defined as tracheostomy and/or chronic oxygen therapy at least 4 hours a day and/or repeated aspiration pneumonia - at least 4 in the last year).
  3. Intractable seizures that started during the last 6 months prior to beginning of the study.
  4. Known hypersensitivity to glatiramer or mannitol.
  5. Participation in another clinical study.
  6. Parents of a patient who are unable to communicate well with the investigator and staff and comply with study procedures and follow-up
  7. Parents of a patient who are unwilling to sign consent form.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02023424

Contacts
Contact: BRURIA BEN ZEEV, MD +972 3 5302687 Bruria.BenZeev@sheba.health.gov.il

Locations
Israel
Sheba Medical Center Recruiting
Ramat Gan, Israel
Contact: BRURIA BEN ZEEV, MD    +972 3 5302687    Bruria.BenZeev@sheba.health.gov.il   
Contact: Irit Avisar, R.N M.A    +972544222786    irit.avisar@sheba.health.gov.il   
Principal Investigator: BRURIA BEN ZEEV, MD         
Sub-Investigator: ANDREEA NISSENKORN, MD         
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Bruria Ben Zeev, prof. Sheba Medical Center
Principal Investigator: Andreea Nissenkorn, Dr. Sheba Medical Center
Study Director: Irit Avisar, R.N M.A Sheba Medical Center
  More Information

No publications provided

Responsible Party: Prof. Bruria Ben-Zeev MD, Head of pediatric neurology unit and Israeli Rett Cener, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT02023424     History of Changes
Other Study ID Numbers: SHEBA-12-9855-BBZ-CTIL
Study First Received: December 23, 2013
Last Updated: February 3, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Sheba Medical Center:
BDNF
GLATIRAMER ACETATE
RETT SYNDROME
COPAXONE
Bruria Ben-Zeev

Additional relevant MeSH terms:
Syndrome
Rett Syndrome
Disease
Pathologic Processes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Copolymer 1
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents

ClinicalTrials.gov processed this record on October 01, 2014