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

NCT02023424 | Unknown Phase 1 DMC

• 1 other identifier: SHEBA-12-9855-BBZ-CTIL
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.To test the hypothesis that 6 months treatment with glatiramer acetate (GA) improves respiratory dysfunction.
2. 2.To evaluate the effect of GA treatment on general behaviour communication, hand stereotyping, feeding, sleep and other autonomic symptoms: gastrointestinal and cardiac.
3. 3.To assess the effect of GA treatment on bodily development.
4. 4.Improvement in the scoring of breath holds and hyperventilation, as measured with non-invasive respiratory inductance plethysmography (NoxT3 device) and parents' diaries.
5. 5.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.
6. 6.Decrease in seizure frequency as reported in parents' diary.
7. 7.Improvement in sleep schedule as recorded in a sleep diary.
8. 8.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.

Conditions

Rett Syndrome

Keywords

BDNF; GLATIRAMER ACETATE; RETT SYNDROME; COPAXONE; Bruria Ben-Zeev

Outcome Measures

Primary Outcomes (1)

• Improvement of epileptiform activity as recorded in a 24-hours EEG.

  6 months

Secondary Outcomes (5)

• 1.Improvement in the scoring of breath holds and hyperventilation, as measured with non-invasive respiratory inductance plethysmography (NoxT3 device) and parents' diaries.

  8 months

• 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.

  8 months

• Decrease in seizure frequency as reported in parents' diary.

  8 months

• Improvement in sleep schedule as recorded in a sleep diary.

  8 months

• Change in height and weight

  8 months

Study Arms (1)

Copaxone

EXPERIMENTAL

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®)

Interventions

Glatiramer Acetate (Copaxone®) DRUG

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.

Copaxone

Eligibility Criteria

• Age: 6 Years - 15 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Females, age 6-15 years (inclusive).
• Patients whose parents or legal custodians have provided written informed consent to participate in the study.
• A diagnosis of RTT (classical or variant), defined according to the internationally agreed 2010 RetSearch criteria \[4\].
• Evidence of a genetically defined pathological change in the MECP2 gene (point mutation or deletion)
• Patients with known epileptiform activity as recorded on EEG.
• 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
• An electrocardiogram (ECG) which, according to the Investigator's judgment does not contraindicate participation in the study.
• No clinically significant abnormalities in haematology, blood chemistry lab tests at screening.
• Parents must be able to understand the requirements of the study and must be willing to comply with the requirements of the study

You may not qualify if:

• 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.
• 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).
• Intractable seizures that started during the last 6 months prior to beginning of the study.
• Known hypersensitivity to glatiramer or mannitol.
• Participation in another clinical study.
• Parents of a patient who are unable to communicate well with the investigator and staff and comply with study procedures and follow-up
• Parents of a patient who are unwilling to sign consent form.

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Sheba Medical Center

Ramat Gan, Israel

RECRUITING

MeSH Terms

Conditions

Rett Syndrome

Interventions

Glatiramer Acetate

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Bruria Ben Zeev, prof.

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

• Andreea Nissenkorn, Dr.

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

• Irit Avisar, R.N M.A

  Sheba Medical Center

  STUDY DIRECTOR

Central Study Contacts

BRURIA BEN ZEEV, MD

CONTACT

+972 3 5302687; Bruria.BenZeev@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of pediatric neurology unit and Israeli Rett Cener

Study Record Dates

• First Submitted: December 23, 2013
• First Posted: December 30, 2013
• Study Start: January 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: February 1, 2015
• Last Updated: February 4, 2014

Record last verified: 2014-02

Locations

IL (1)