Trial of Kuvan™ (Sapropterin) Treatment in Patients With Lesch Nyhan Disease
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Clinical responses to be monitored will include frequency and severity of self mutilation episodes, frequency and severity of aggressive acts towards others, and any effect on involuntary movements.
研究概览
简要总结
To assess the possibility that treatment with Kuvan (a form of tetrahydrobiopterin) will lessen the abnormal behavior and/or neurology commonly found in Lesch-Nyhan disease (LND); to assess biochemical changes as measured in blood and urine.
详细描述
Lesch-Nyhan disease (LND) is an X-linked disorder of purine metabolism which results from mutation in the gene for the enzyme hypoxanthineguanine phosphoribosyltransferase (HPRT); patients have hyperuricemia, gout, urinary tract calculi, and nephropathy which are effectively treated with allopurinol. There is also a syndrome of dystonia, chorea and athetosis, as well as involuntary self mutilative biting and aggression toward their caretakers, for which there is no treatment.
Kuvan™ is a form of tetrahydrobiopterin (BH4), and is approved to help lower the blood levels of phenylalanine in people who have phenylketonuria (PKU). LND patients have been found to have decreased BH4 in the spinal fluid and brain; BH4 is a precursor of dopamine, which has an effect on behavior. In an earlier study Dr Nyhan found that treatment of LND with 5-hydroxytryptophan and carbidopa abolished the self-injurious behavior but was uniformly transient.
This is a single site open-label protocol for eight subjects age 4 years and older with Lesch-Nyhan Disease documented by deficiency of HPRT.
The study involves three study visits to San Diego and one study visit done locally. The first visit will last 13 days, the following visits are single day visits at week 4 and week 8, and the local study visit is a brief outpatient visit at week 6. Physical and neurological exams, videotaping of the patient's interactions with the study staff, and blood and urine collection for laboratory analyses will be performed at each San Diego visit. A family member or caregiver will be asked to complete a short assessment form and report any illness or medication changes. In addition, the study staff will have weekly telephone contact with the family to discuss any behavioral changes or study drug issues.
If the patient's self injurious behavior becomes worse after starting Kuvan the drug will be discontinued and the patient will be followed until the behavior returns to baseline.
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
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 4 years and older
- •Must have documented evidence of HPRT deficiency.
- •Be on a stable treatment regimen for 30 days or more
- •Willing and able to travel to San Diego for the study visits
- •Have a local neurologist or physician familiar with the patient or experienced in managing behavioral/neuromuscular disorders and willing to assist with study procedures and adverse events if necessary
排除标准
- •Concurrent enrollment in an investigational drug study
- •Currently taking levodopa
- •Elevated liver enzymes
- •Renal or liver impairment or disease
- •Inability to comply with required study procedures
研究组 & 干预措施
Kuvan
10mg/kg Kuvan for 5 days followed by 20mg/kg Kuvan for a total of 60 days
干预措施: sapropterin (Drug)
结局指标
主要结局
Clinical responses to be monitored will include frequency and severity of self mutilation episodes, frequency and severity of aggressive acts towards others, and any effect on involuntary movements.
时间窗: Periodically during the eight weeks of treatment per patient
次要结局
- Effect of Kuvan on standard chemistries, plasma amino acids, and plasma and urinary catecholamines(Assessed periodically during treatment)