Baseline Evaluation and Long-term Follow-up of Nutritional Status and Neurotransmitter Concentrations in Phenylketonuria Patients Initiating Treatment With Sapropterin Dihydrochloride (KuvanTM), a Tetrahydrobiopterin Analog.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 2
- 主要终点
- Change From Baseline in BMI at 12 Months
研究概览
简要总结
HYPOTHESIS: The investigators hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects.
SUMMARY: Though the investigators know that KuvanTM lowers blood Phe levels and improves tolerance for natural protein in at least half of the PKU (Phenylketonuria) patient population, investigators do not know the full effects this medicine will have on the patient's diet, or what impact the medicine or diet changes will have on the body composition or nutrient status of PKU patients. Since KuvanTM may also help the body produce neurotransmitters, investigators also want to find out if taking KuvanTM changes neurotransmitter levels in PKU patients, and if PKU patients who are benefitting from KuvanTM feel less stigmatized and have a better outlook on life as a result of the treatment.
Therefore, the research study has several objectives. These are to investigate the impact KuvanTM therapy has on (1) body composition parameters of PKU patients: such as lean body mass, percent body fat, bone density, weight gain, and growth (2) dietary changes, and the effect of those changes, on intake of calories and essential nutrients (3) changes in blood biomarkers of certain nutrients (4) blood and urine neurotransmitter levels, since these changes could indicate improved neurological functioning, (5) and quality of life of PKU patients, who may feel less burdened due to the dietary freedom KuvanTM provides.
详细描述
BACKGROUND : Tetrahydrobiopterin (BH4) is a treatment option newly available to phenylketonuria (PKU) patients within the United States as the pharmaceutical KuvanTM. This small molecule functions as a cofactor in multiple enzyme systems, including the metabolism of phenylalanine into tyrosine by the enzyme phenylalanine hydroxylase (PAH).
HYPOTHESIS
The investigators hypothesize that KuvanTM therapy could influence nutritional and body composition parameters and neurotransmitter concentrations in pediatric and adult PKU subjects.
OBJECTIVES:
- To record nutritional biomarkers, body composition, bone density, and measures of nutrient intake in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
- To investigate changes in monoamine neurotransmitter synthesis in a phenylketonuria subject group at baseline and for one year after start of KuvanTM therapy.
- Evaluate changes in quality of life (QOL) for PKU subjects beginning KuvanTM therapy
METHODOLOGY: Investigators intend to enroll 60 PKU patients, ages 4 to adulthood, who are planning to begin BH4 treatment as prescribed by their medical provider. Patients will be given 4 weeks to demonstrate a response to KuvanTM as determined by a drop in plasma PHE by ≥15%. All patients, regardless of response to KuvanTM, will be allowed to continue in the study. All subjects will be followed for a full 12 months while monitoring nutrient intake, nutritional biomarkers, serotonin and catecholamine levels, and QOL. Two-tailed statistical analysis with α=0.05 will be used to compare results between responders and nonresponders, as well as compare follow-up values with baseline measures.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- 是
入选标准
- •Diagnosed with PKU
- •ability to provide informed consent (or have legal guardian who can provide informed consent)
- •at least 4 years of age
- •planning on trying BH4 treatment
排除标准
- •unable to provide informed consent
- •less than 4 years of age
- •currently taking BH4
研究组 & 干预措施
PKU subjects - baseline
Male and female subjects with PKU at baseline starting KuvanTM therapy.
干预措施: KuvanTM Therapy (Drug)
结局指标
主要结局
Change From Baseline in BMI at 12 Months
时间窗: Baseline and 12 months
Change in Body mass index (BMI) from baseline of Kuvan study to 12 months post-baseline
Change From Baseline in Plasma Phenylalanine at 12 Months
时间窗: Baseline and 12 months
Full amino acid panel, including phenylalanine, analyzed in fasting plasma samples.
Change From Baseline in Phenylalanine Intake at 12 Months
时间窗: Baseline and 12 months
Total dietary phenylalanine assessed through 3-day food records - calculated as average phenylalanine intake (grams/day) in the 3 days recorded
Change From Baseline in Bone Mineral Density (BMD) at 12 Months
时间窗: Baseline and 12 months
Change in bone mineral density (BMD) from baseline of Kuvan study to 12 months post-baseline
Change From Baseline in Percent (%) Fat Mass at 12 Months
时间窗: Baseline and 12 months
Percent fat mass measured via dual energy x-ray absorptiometry (DXA)
Change From Baseline in Total Dietary Protein Intake at 12 Months
时间窗: Baseline and 12 months
Total dietary protein intake assessed through 3-day food records - calculated as average protein intake (grams/day) in the 3 days recorded
Change From Baseline in Percent (%) Lean Mass at 12 Months
时间窗: Baseline and 12 months
% lean mass was measured via dual energy x-ray absorptiometry (DXA)
次要结局
未报告次要终点
研究者
Rani Singh
Associate Professor
Emory University