Therapeutic and Metabolic Studies of Urea Cycle Disorders: Part A: Nitrogen Flux and Ureagenesis; Part B (Closed): Phase I Adenovirus Vector-Mediated Gene Therapy for Ornithine Transcarbamylase Deficiency
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 66
- 试验地点
- 2
研究概览
简要总结
RATIONALE: The urea cycle is the process in which nitrogen is removed from the blood and converted into urea, a waste product found in urine . Urea cycle disorders are inherited disorders caused by the lack of an enzyme that removes ammonia from the bloodstream. Gene therapy is treatment given to change a gene so that it functions normally. Studying the treatment and metabolism of patients with urea cycle disorders may be helpful in developing new treatments for these disorders.
PURPOSE: Two-part clinical trial to study the treatment and metabolism of patients who have urea cycle disorders.
详细描述
PROTOCOL OUTLINE: This protocol involves 2 clinical studies. Part A is a metabolic study of glutamine conversion to urea at different levels of protein intake, while on and off medications. Part B is a dose escalation study of a first-generation adenoviral vector with an E1 deletion and an E3 deletion substitution (d1309) expressing ornithine transcarbamylase (OTC).
In Part A, diet is controlled for protein and calories. Intravenous glutamine and urea are administered. Controls are given intravenous arginine, phenylacetate, and benzoate.
In Part B, groups of 3 patients are given a single low, intermediate, or high dose of intravenous OTC vector. Allopurinol is administered every 12 hours for 12 days. As of 12/10/1999, Part B of the study is closed.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 6 Months 至 64 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •PROTOCOL ENTRY CRITERIA:
- •Part A. Patients at least 6 months old with ornithine transcarbamylase deficiency (OTC), i.e.: Hemizygous OTC or homozygous autosomal recessive disorder with evidence of complete enzyme deficiency Hemizygous OTC male with late presentation and presumed evidence for residual enzyme activity OTC heterozygotes (molecular diagnosis) with severely symptomatic to asymptomatic disease Obligate heterozygotes for autosomal recessive disorder (parent or genotyped sibling) Normal adult volunteers and genotyped siblings entered as controls Part B. Metabolically stable heterozygous OTC females aged 18 to under 65 Orotic acid level at least 5 times normal on allopurinol Symptoms ranging from severe to asymptomatic acceptable No prior hospitalization for hyperammonemia
排除标准
- •(Parts A and B): Acute or chronic intercurrent illness Pregnancy Acute hyperammonemia