Phase 2 Study of Glycomacropeptide vs. Amino Acid Diet for the Management of PKU

糖巨肽与氨基酸饮食治疗 PKU 的 2 期研究

• 批准号: 8022162
• 负责人: Harvey L. Levy
• 金额: $ 39.79万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8022162
• 关键词: Phase; Study; Glycomacropeptide; vs.; Amino

DESCRIPTION (provided by applicant): Individuals with PKU lack the enzyme phenylalanine hydroxylase that is needed to metabolize the essential amino acid phenylalanine (phe). When eating a normal diet they show an elevated level of phe in blood that is toxic to the brain. In order to prevent brain damage and cognitive impairment, individuals with PKU must follow a lifelong, low-phe diet that is restricted in natural foods and requires ingestion of a phe-free amino acid (AA) formula. Most adolescents and adults with PKU find the AA formula unpalatable and go off the diet resulting in elevated blood phe levels and neuropsychological deterioration. The risk and potential health care costs are especially high for pregnant women with PKU whose infants show congenital anomalies when exposed to elevated maternal blood phe levels, i.e., maternal PKU. Glycomacropeptide (GMP), an intact protein produced during cheese making, is uniquely suited to a low-phe diet because it is the only known dietary protein that contains minimal phe. Foods and beverages made with GMP are a palatable alternative to AA formula. The long-term goal is to assess the safety, efficacy and acceptability of GMP for the nutritional management of PKU. The specific aim is to conduct a randomized, two-stage, 11-week (wk), crossover trial comparing the GMP diet with the AA diet in 30 subjects with PKU =12 years of age treated since birth with a low-phe AA diet. The sites are: University of Wisconsin- Madison, Waisman Center (primary) and Harvard University, Children's Hospital Boston. Subjects will be recruited and randomized to begin the first 3-wk of the study with either a low phe diet in which the majority of dietary protein is provided by GMP or AA medical foods and then, after a 3-wk washout with intake of their usual diet, begin the second diet for 3-wk. Dietary education will be provided in a 1-wk base period preceding initiation of each diet. The primary endpoint is change in the plasma phe concentration of PKU subjects fed the GMP diet for 3-wk compared with change in the plasma phe concentration when fed the AA diet for 3-wk (paired t-test, pairing on subject). Secondary outcome variables include compliance assessed by food records, acceptability assessed by questionnaires, and cognitive function assessed by neuropsychological tests. The investigators expect that compared to the usual AA diet, the GMP diet will reduce plasma phe levels and improve cognitive function due to improved dietary compliance and phe utilization. To enhance understanding of the etiology of low bone mass, a common long-term complication in those with PKU, exploratory data will be obtained to assess markers of bone turnover in a subset of 20 PKU subjects, 12-20 years of age.

描述（由申请人提供）： 患有PKU的个体缺乏代谢氨基酸苯丙氨酸（PHE）所需的酶苯丙氨酸羟化酶。 吃正常饮食时，它们显示出对大脑有毒的血液中PHE水平升高。为了防止脑损伤和认知障碍，患有PKU的个体必须遵循终生，低饮食的饮食，该饮食受到天然食品的限制，需要摄入无PHE氨基酸（AA）配方。 大多数患有PKU的青少年和成年人都发现AA公式不可能，并消除饮食，导致血液phe水平升高和神经心理学恶化。 对于患有PKU的孕妇的风险和潜在的医疗保健费用尤其很高，这些孕妇的婴儿暴露于母体血液PHE水平升高时，即产妇PKU。 糖氨基肽（GMP）是一种在制作奶酪过程中产生的完整蛋白质，非常适合低phe饮食，因为它是唯一已知的饮食蛋白，其中含有最小的PHE。 用GMP制造的食品和饮料是AA配方的可口替代品。 长期目标是评估GMP对PKU营养管理的安全性，功效和可接受性。 具体的目的是进行一项随机的，两阶段的，11周（WK）的跨界试验，将30名受试者的GMP饮食与AA饮食进行比较，PKU =自phe AA饮食低=以来，PKU = 12岁。这些地点是：威斯康星大学 - 麦迪逊大学，威斯曼中心（小学）和波士顿儿童医院的哈佛大学。 受试者将被招募并随机分配，以低PHE饮食开始研究的第一个3周，其中大多数饮食蛋白是由GMP或AA医疗食品提供的，然后在摄入通常饮食的3周清洗后，开始了第二次饮食，请开始使用第二次饮食。 每种饮食开始之前的1周基本期间，将提供饮食教育。 主要终点是与在3周喂食AA饮食时血浆PHE浓度的PKU受试者血浆PHE浓度的变化相比（配对t检验，对受试者配对）。 次要结果变量包括通过食物记录评估的合规性，通过问卷评估的可接受性以及通过神经心理学测试评估的认知功能。 研究人员预计，与通常的AA饮食相比，GMP饮食将降低血浆PHE水平，并因改善饮食的依从性和PHE利用而提高认知功能。为了增强对低骨质的病因的理解，PKU患者的常见长期并发症将获得探索性数据，以评估20个PKU受试者（12-20岁）的子集中的骨转换标记。