Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Incidence of adverses events reported during the study
研究概览
简要总结
Fragile X Syndrome (FXS) is caused by loss of FMR1 expression on the X chromosome that leads to increased mRNA translation, which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rifampicin complex 1) signalling and consequently in synaptic dysfunction and neurological development. There is presently no cure for FXS. Recent studies suggest that metformin (a widely prescribed drug for type II diabetes in children and adults) which crosses the blood-brain barrier, corrects various neurological and behavioral FXS phenotypes by normalizing ERK signaling, EIF4E phosphorylation and lowering expression of MMP9 to normal. Since this drug has not been previously used specifically for treatment of FXS (only few cases reported), the investigators propose an open-label trial of metformin in children and adults with FXS to better understand the safety and efficacy in both behavior and cognition.
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 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged between 10 et 45 years old
- •BMI > 18.3
- •Molecular diagnosis of FXS
- •Accompanied by his legal tutor
排除标准
- •Pregnancy/Breastfeeding
- •Intolerance to metformin
- •History of lactic acidosis
- •Gastric/renal/hepatic pathology
- •Acute medical condition
- •Concomitant use of ACE inhibitors
- •Modification of antipsychotic treatments in the last 6 weeks
研究组 & 干预措施
Metformin
Metformin 500mg twice a day per os for 9 weeks
干预措施: Metformin (Drug)
结局指标
主要结局
Incidence of adverses events reported during the study
时间窗: 9 weeks
Number and severity of adverse events related to metformin treatment
Change from baseline in the total score of the FX-normed Aberrant Behavior Checklist-Community after 9 weeks of metformin treatment
时间窗: Baseline, Week 9
The ABC-C is a 58-item caregiver-rated behavior scale where each item ranges from 0 (not a problem) to 3 (severe problem).
次要结局
- Changes from baseline in the Global Executive Composite (GEC) baseline score of the Behavior Rating Inventory of Executive Function (BRIEF)(Baseline, Week 9)
- Level of synaptic plasticity using Electroencephalography (EEG)(Baseline, Week 9)
- Changes from baseline in the score of each subscale of the Aberrant Behavior Checklist-Community (ABC-C)(Baseline, Week 9)
- Changes from baseline in the score of 4 subtests of the computerized cognitive Test of Attentional Performance for Children(Baseline, Week 9)
- Level of cortical excitability using Transcranial Magnetic Stimulation (TMS)(Baseline, Week 9)
研究者
Çaku
Principal Investigator
Université de Sherbrooke