Safety and Efficacy of Treatment With Large Neutral Amino Acids in Patients With Classical Phenylketonuria
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 3
- 主要终点
- Dynamic positron emission tomography (PET) imaging with the fluorine-18-labeled tracer [18F]-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl phenyl)nortropane ([18F]FE-PE2I)
研究概览
简要总结
This research investigates the effectiveness and safety of large neutral amino acid (LNAA) supplementation in patients with classical phenylketonuria (PKU). Advanced brain imaging techniques alongside comprehensive neuropsychological and functional assessments will be employed. Short-term and long-term follow-up of participants will be conducted.
详细描述
Standard treatment for Phenylketonuria (PKU) involves a lifelong, phenylalanine-restricted diet. Strict adherence to the diet is crucial, but often challenging. Large neutral amino acid (LNAA) supplementation is a potential alternative therapeutic approach for PKU management. The proposed mechanism involves competitive inhibition of phenylalanine (Phe) transport across the blood-brain barrier by high-dose LNAA, leading to reduced brain Phe levels. However, further investigation is needed to validate its efficacy and safety for PKU management.
Two separate crossover studies will be conducted to assess the safety and efficacy of LNAA supplementation in PKU patients.
Study 1: LNAA vs. No Treatment: This crossover trial investigates the effects of LNAA supplementation compared to no treatment. Participants will undergo both treatment phases in a randomized order:
- Phase 1: Semi-free diet with LNAA [duration: 8 weeks]
- Phase 2: Semi-free diet with no supplementation [duration: 1 week]
Study 2: LNAA vs. Phe-restricted Diet: This crossover trial compares LNAA supplementation to the current standard treatment, the Phe-restricted diet. Participants will undergo both treatment phases in a randomized order:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Treatment initiation within the first month of life (ideally < 10 days of age)
- •Intelligence quotient (> 84) based upon the baseline neuropsychological evaluation
- •Conventional dietary treatment up to minimum 15 years of age
- •Written informed consent
- •Willing and able to comply with the protocol and study procedures
排除标准
- •Unable or unwilling to adhere to the requirements of the study
- •A female who is pregnant or breastfeeding or planning to get pregnant during the study period
- •Concomitant medication that may interfere with the PET analysis, as judged by the investigator
- •A serious neuropsychiatric disease that could interfere with the subject's ability to participate in the study at the discretion of the investigator
- •Concomitant treatment with sapropterin (BH4) supplementation or Pegvaliase-pqpz (PALYNZIQ)
- •Failing to submit at least one blood Phe home sample during the year before study initiation
- •Standard MRI contraindications
结局指标
主要结局
Dynamic positron emission tomography (PET) imaging with the fluorine-18-labeled tracer [18F]-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl phenyl)nortropane ([18F]FE-PE2I)
时间窗: Crossover study: at 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline
Change in specific binding ratio of dopamine transporter (DaT) with \[18F\]FE-PE2I
次要结局
- Urine peripheral biomarkers of neurotransmitters(Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline)
- Incidence and severity of treatment-emergent adverse events (TEAEs)(Baseline to week 80)
- Adult attention deficit hyperactivity disorder (ADHD) Self-Report Scale (ASRS v1.1)(Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline)
- Symptom Checklist-90-Revised (SCL-90-R)(Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline)
- Neuropsychological testing of flexibility and verbal fluency(Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline)
- Behaviour Rating Inventory of Executive Function - Adult version (BRIEF-A)(Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline)
- PKU-QOL Questionnaire Adult version(Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline)
- Computerized neuropsychological testing (responses over study iPad)(Crossover study: at baseline, 8, 10 and 18 weeks from baseline, Extension study: at 12 months from baseline)
研究者
Allan Meldgaard Lund
Professor, MD, DMSc
Rigshospitalet, Denmark