Palynziq and PKU: Treatment Impacts on Diet Quality, Neurological Health, Nutritional Status, and the Metabolome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Intra-subject Change in Intact Protein Intake
研究概览
简要总结
Phenylketonuria (PKU) is an inherited metabolic disorder that impairs the metabolism of the essential amino acid phenylalanine (Phe). Without stringent dietary control, Phe accumulates in the blood and brain of PKU patients, leading to severe cognitive deficits. Achieving metabolic control, defined as blood Phe levels within the range of 120-360 μmol/L, has been a significant challenge for PKU patients using traditional diet therapy. The new FDA approved pharmacologic treatment, Palynziq, offers a new approach that could significantly reduce the burden of PKU by improving blood Phe levels and allowing for a less restrictive diet. As little is known about the global metabolic and physiologic effects of Palynziq, the present study aims to capture changes in diet quality, neurological health, nutritional status, the nutritional metabolome, and patient perceptions of mental and social health with sustained Palynziq therapy.
详细描述
Phenylketonuria (PKU) is an autosomal recessive disorder caused by more than 500 pathogenic variants in the phenylalanine hydroxylase (PAH) gene. Due to these mutations, affected individuals have reduced activity or complete deficiency of the enzyme phenylalanine hydroxylase, which metabolizes the essential amino acid phenylalanine (Phe) to tyrosine. Consequently, Phe and its byproducts accumulate in the blood and brain of PKU patients, which can have irreparable physical and neurocognitive effects. These may include intellectual disabilities, seizures, eczema, psychosis, and hypopigmentation. To prevent these adverse conditions, early diagnosis and meticulous control of blood Phe levels are required. For optimal metabolic control, the American College of Medical Genetics (ACMG) recommends lifelong maintenance of Phe concentrations within the range of 120-360 μmol/L.
Diet therapy has dramatically improved metabolic control and nutritional status in PKU patients and when adherent to dietary treatment, numerous patients have been able to achieve normal growth and prevent severe cognitive deficits. This, however, is not an easy task given a steep restriction of intact protein is required to keep blood Phe levels within the therapeutic range. To meet nutritional needs in the absence of dietary protein, patients consume large volumes of Phe-free amino acid formulas (medical food) and specialized low-protein modified foods. While this regimen may improve overall diet quality, due to the fortification of formula with vitamins and minerals, the poor palatability and high cost medical food makes diet therapy a significant burden for patients and their families.
Pharmacologic therapies now provide an innovative approach to improve patient health and quality of life by liberalizing the traditional protein-restricted diet. Palynziq is a PEGylated recombinant of phenylalanine lyase, which can lower blood Phe concentrations. Given increasing numbers of PKU patients will be initiating Palynziq therapy, it is essential to prospectively evaluate the impact of this novel treatment on the neurological health, diet quality, and nutritional metabolome of patients when administered in a clinical setting. This knowledge will not only improve the efficacy of the treatment, but will be essential for expanding the current dietary guidelines to meet the unique needs of patients treated with Palynziq.
The objectives of this proposal are to obtain information on the diet quality, neurological health, and nutritional metabolome of patients with PKU at baseline and after intervention with Palynziq. This is a three-year observational study that includes non-pregnant adults who have PKU and have obtained a physician's prescription to initiate Palynziq treatment. Patients who complete the three year study are now eligible to participate in a sub-study which extends the main protocol for up to five years.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •16 years of age or older
- •diagnosed with PKU through newborn screening or via diagnosis later in life
- •capable of providing consent for medical tests and procedures
- •prescription for Palynziq and be enrolled in the Palynziq Risk Evaluation and Mitigation Strategy (REMS) program
- •Substudy: Participants must have completed visit 2 of the main study
排除标准
- •unable to provide consent
- •a diagnosis of, or take medication for psychiatric, behavioral, or other inherited metabolic disorders
研究组 & 干预措施
Palynziq Therapy for PKU
Participants with PKU who are starting Palynziq therapy, or have recently started Palynziq therapy but have not achieved response.
干预措施: Palynziq (Drug)
结局指标
主要结局
Intra-subject Change in Intact Protein Intake
时间窗: Baseline through 12 Months Post-Response (up to 14 months after baseline)
Intra-subject change in intact protein intake will be assessed by participant-reported 3-day dietary records.
Intra-subject Change in Medical Food Protein Intake
时间窗: Baseline through 12 Months Post-Response (up to 14 months after baseline)
Intra-subject change in medical food protein intake will be assessed by participant-reported 3-day dietary records.
Sub study: Intra-subject change in intact protein and medical food protein intake.
时间窗: 12 Months Post-Response through additional five years (6 years post-response)
Intra-subject change in medical food protein intake will be assessed by participant-reported 3-day dietary records.
次要结局
- Change in Average Intact Protein Intake(Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline))
- Days From Palynziq Initiation to Response(Baseline up to Response (up to 60 days))
- Change in Neuro-QOL - Cognitive Function - Short Form Score(Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline))
- Days From Palynziq Initiation to Consumption of Dietary Reference Intake for Intact Protein(Baseline up to 12 Months Post-Response (up to 14 months after baseline))
- Change in Plasma Amino Acids(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Intra-subject Change in Percent Lean Body Mass(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Sub-Study: Change in Plasma Neurotransmitters(12 Months Post-Response through additional five years (6 years post-response))
- Sub-Study: Change in The Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score(12 Months Post-Response through additional five years (6 years post-response))
- Change in Neuro-QOL Sleep Disturbance - Short Form Score(Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline))
- Change in Essential Fatty Acids(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Intra-subject Change in Percent Fat Body Mass(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Sub-Study: Change in PROMIS-29 Anxiety and Depression Score(12 Months Post-Response through additional five years (6 years post-response))
- Change in The Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score(Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline))
- Intra-subject Change in Resting Energy Expenditure(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Sub-Study: Change in PROMIS Emotional Support Score(12 Months Post-Response through additional five years (6 years post-response))
- Change in PROMIS-29 Anxiety and Depression Score(Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline))
- Change in PROMIS Emotional Support Score(Baseline, Response (up to 60 days) 12 Months Post-Response (up to 14 months after baseline))
- Change in Plasma Neurotransmitters(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Intra-subject Change in Bone Mineral Density(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Intra-subject Change in Grip Strength(Baseline through 12 Months Post-Response (up to 14 months after baseline))
- Sub-Study: Change in Neuro-QOL - Cognitive Function - Short Form Score(12 Months Post-Response through additional five years (6 years post-response))
- Sub-Study: Change in Neuro-QOL Sleep Disturbance - Short Form Score(12 Months Post-Response through additional five years (6 years post-response))