Phase I/II Trial of Valproic Acid and Carnitine in Infants With Spinal Muscular Atrophy Type I (CARNI-VAL Type I)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 8
- 主要终点
- Anthropometric Measures of Nutritional Status (Body Mass Index [BMI] Z-scores, Weight for Length Ratios, Lean/Fat Mass Via DEXA, Growth Parameters, and Triceps Skinfold Measures)
研究概览
简要总结
This is a multi-center trial to test safety and evaluate early treatment intervention with valproic acid and carnitine in moderating SMA symptoms of Type I infants.
详细描述
Spinal muscular atrophy (SMA) is a genetic disorder that results in severe muscle weakness. It is one of the most common conditions causing muscle weakness in children. Patients with SMA most often develop weakness as babies or young children. Most people with SMA gradually lose muscle strength and abilities over time. Babies with the severe infantile form of SMA, SMA type I, usually lose abilities and strength quickly over a few weeks or months.
Valproic acid (VPA) is a medicine that has been used for many years to treat patients with epilepsy. Recent research suggests that VPA may be able to upregulate expression of a backup copy of the SMN gene in SMA patient cell lines. In addition, some preliminary data suggests it may prolong survival in animal models of SMA. Because VPA can deplete carnitine in children with SMA Type I, carnitine is added to help prevent possible toxicity.
In this multi-center trial, we will evaluate the effects of VPA/carnitine on infants with SMA type I. A variety of outcome measures, including assessment of safety, will be performed at each study visit to follow the course of the disease. The protocol includes two baseline visits over a period of two weeks, two clinical assessments on medication at 3 and 6 months, and then 6 months additional followup via telephone. Total duration of the study will be approximately 12 months.
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
- 2 Weeks 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Laboratory documentation of SMN mutation/deletion consistent with a genetic diagnosis of SMA
- •Clinical diagnosis of SMA type I
- •Age 2 weeks to 12 months
- •Written informed consent of parents/guardian
排除标准
- •Any clinical or laboratory evidence of hepatic or pancreatic insufficiency.
- •Laboratory results drawn within 14 days prior to start of study drug demonstrating:
- •Liver transaminases (AST, ALT), lipase, amylase: > 1.5 x ULN White Blood Cell Count: < 3 Neutropenia: <1 Platelet: <100K Hematocrit: <30, persisting over a 30-day period
- •Serious illness requiring systemic treatment and/or hospitalization within two weeks prior to study entry.
- •Use of medications or supplements within 30 days of study enrollment that interfere with VPA or carnitine metabolism; that increase the potential risks of VPA or carnitine; or that are hypothesized to have a beneficial effect in SMA animal models or human neuromuscular disorders, including riluzole, valproic acid, hydroxyurea, oral use of albuterol, sodium phenylbutyrate, butyrate derivatives, creatinine, growth hormone, anabolic steroids, probenecid, oral or parenteral use of corticosteroids at entry, or agents anticipated to increase or decrease muscle strength or agents with presumed histone deacetylase (HDAC) inhibition.
- •Infants who have participated in a treatment trial for SMA within 30 days of study entry or who will become enrollees in any other treatment trial during the course of this study.
- •Unwillingness to travel for study assessments.
- •Coexisting medical conditions that contradict use of VPA/carnitine or travel to and from study site.
研究组 & 干预措施
1
All patients will receive VPA and carnitine.
干预措施: Valproic Acid and Levocarnitine (Drug)
结局指标
主要结局
Anthropometric Measures of Nutritional Status (Body Mass Index [BMI] Z-scores, Weight for Length Ratios, Lean/Fat Mass Via DEXA, Growth Parameters, and Triceps Skinfold Measures)
时间窗: -2 weeks, time 0, 3 months, 6 months
Laboratory Safety Data
时间窗: -2 weeks, + 2 weeks, 3 months, 6 months
次要结局
- Functional Motor Assessments: TIMPSI Scores(-2 weeks, time 0, 3 months, 6 months)
- Quantitative SMN mRNA and Protein Measures(-2 weeks, time 0 , 3 months, or 6 months)
- Primary Caregiver Functional Rating Scale for SMA Type I Subjects (PCFRS)(time 0, and monthly for 12 months)
- Maximum Ulnar CMAP Amplitude/Area and MUNE(-2 weeks, time 0, 3 months, 6 months)
- Time to Death or Ventilator Dependence (Defined as >16 Hours/Day)(monthly)
- Whole Body DEXA Scanning for Lean Body Mass and Total Bone Mineral Density/ Content(-2 weeks or time 0, 3 months, 6 months)
研究者
Kathryn Swoboda
Associate Professor, Neurology and Pediatrics Director, Pediatric Motor Disorders Research Program
University of Utah