Quantitative Requirements of Docosahexaenoic Acid for Neural Function in Children With Phenylketonuria
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 8
- 主要终点
- latency of visually evoked potentials
研究概览
简要总结
Patients with phenylketonuria (PKU) have an inborn error in the metabolism of the amino acid phenylalanine (Phe) and thus must follow a strictly controlled protein-restricted diet from early infancy. This protein-restricted diet is devoid of natural dietary sources of n-3 long chain polyunsaturated fatty acids (LC-PUFA), such as eggs, meat, milk or fish. Therefore, blood concentrations of n-3 LC-PUFA, especially of docosahexaenoic acid (DHA) are reduced in PKU children compared to healthy controls. DHA availability is considered important for optimal neurological function. Previous studies have shown that neural function of PKU children is improved by high dose supplementation of fish oil providing DHA, as shown by significant improvements of both visual evoked potential latencies and of fine motor skills and coordination, but no dose response relationship has been established so far.
This multicentric double-blind randomized trial aims at determining quantitative DHA requirements for optimal neural function in PKU children. Patients with classical PKU from several major treatment centers in Europe will be randomized to receive between 0 and 8 mg of DHA per kg body weight daily for a duration of 6 months. Biochemical (fatty acid composition of plasma phospholipids, lipoprotein metabolism and metabolic profiles), and functional testing (visual evoked potentials, fine motor skills, cognitive function and markers of immune function) will be performed at baseline and after 6 months. Intake per kg body weight will be related to outcome parameters and thus a possible dose response relationship will be defined. The results from this study are expected to contribute to the improvement of the diet of PKU patients, but they also have the potential to help defining quantitative DHA needs of healthy children.
The primary hypothesis is that supplementation with DHA improves visual function in children with PKU.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 13 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children with classical PKU, who have been diagnosed and treated from the newborn period onwards
- •Classical PKU must have been established by a baseline plasma phenylalanine (PHE) level >1200 µmol/L or detection of underlying mutations
- •Children are clinically healthy besides classical PKU
- •Good metabolic control (a minimum of 2 Phe-values during the last 6 months are needed with average Phe values being below 480 µmol/L in the last 6 months)
- •No n-3 LC-PUFA supplementation for at least 6 months before enrolment
- •Written informed consent of parents exists
排除标准
- •Severe neurological symptoms
- •History of neurological disease
- •Children are unable to take DHA-capsules regularly
- •Acute illness, especially infections at the time of clinical examination/testing
- •Children with weight/height over the 97th percentile or below the 3rd percentile
- •Known hypersensitivity to fish oil products
结局指标
主要结局
latency of visually evoked potentials
时间窗: assessed basally (before intervention start) and at the end of the 6 month intervention period
次要结局
- fatty acid composition of plasma phospholipids(assessed basally (before intervention start) and at the end of the 6 month intervention period)
- test of reaction time(assessed basally (before intervention start) and at the end of the 6 month intervention period)
- fine motor skills(assessed basally (before intervention start) and at the end of the 6 month intervention period)
研究者
Prof. Berthold Koletzko
Prof.
Ludwig-Maximilians - University of Munich