Pharmacological Treatment of Rett Syndrome With Glatiramer Acetate (Copaxone)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Gait Velocity as Measured by GAITRite System
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Copaxone
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.
干预措施: Glatiramer Acetate (Drug)
结局指标
主要结局
Gait Velocity as Measured by GAITRite System
时间窗: 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.
次要结局
- Visual Memory Novelty Score as Assessed by TX300 Tobii Computer.(Baseline and Final week of treatment (week 32))
- Breath Hold Time (Assessed in the Sleep Monitoring Lab)(Baseline and Final week of treatment (week 32))
- Visual Attention (Number of Fixations) Assessed by Eye-tracking TX300 Tobii Computer.(Baseline and Final week of treatment (week 32))
- Breath Hold Index (Number of Breath Holds Per Hour; Assessed in the Sleep Monitoring Lab)(Baseline and during final week of treatment (week 32))
- Visual Attention (Fixation Length) Assessed by Eye-tracking TX300 Tobii Computer.(Baseline and Final week of treatment (week 32))
研究者
Aleksandra Djukic
Associate Professor of Clinical Neurology and Clinical Pediatrics, Director, Tri State Rett Syndrome Center
Montefiore Medical Center