Neurodevelopmental Outcome of Early Dietary Lysine Restriction in Pyridoxine
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 7
- 主要终点
- Neurocognitive development at age 3 years
研究概览
简要总结
Restricting dietary lysine intake in infants from age 3 months or less with confirmed diagnosis of pyridoxine-dependent epilepsy due to Antiquitin (ATQ) deficiency will: reduce the accumulation of neurotoxic substratesα-aminoadipicsemialdehydeandits cyclic equivalent 1-piperideine-6-carboxylate;and will improve overall neurodevelopmental outcome at 3 years of age by acting as an effective intervention into the complex pathophysiology of the condition.
详细描述
I Purpose: The purpose of this multi-centre study is to further assess the safety and efficacy of the proposed lysine restricted diet in confirmed ATQ deficient PDE patients.
II Hypothesis: Restricting dietary lysine intake in infants from age 3 months or less with confirmed diagnosis of pyridoxine-dependent epilepsy due to Antiquitin (ATQ) deficiency will: reduce the accumulation of neurotoxic substratesα-aminoadipicsemialdehydeandits cyclic equivalent 1-piperideine-6-carboxylate;and will improve overall neurodevelopmental outcome at 3 years of age by acting as an effective intervention into the complex pathophysiology of the condition.
III Justification: We hope that participants have a much improved chance to avoid the same degree of developmental delay and associated problems. If this study demonstrates a significant improvement of normal development and proves to be safe to use this would provide a positive benefit to the child, the families involved as well as decreasing the burden on the health care system which currently must provide for life long care of these affected children.
IV Objectives: To determine the safety and efficacy of the lysine restricted diet on numerous primary and secondary outcome measures as listed in the protocol. The primary objective of this study is to evaluate neurodevelopmental outcome based on neuropsychological assessments using Bayley-III.
V Research Method:
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
- 3 Months 至 3 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of pyridoxine-dependent epilepsy based on clinical symptoms and elevated levels of plasma or urine AASA. Confirmation by at least one known disease causing mutation in the ALDH7A1 gene to be obtained within one month of enrollment.
- •Participant is male or female <3 years of age.
- •Participants in the test arm have to be less than 3 months of age when the dietary restriction was started.
- •Participants in the control arm may be older than 3 months of age but must not be older than 3 years of age when they are enrolled into the study and must have been on pyridoxine treatment prior to age 3 months and not treated with dietary lysine restriction at any time during their life.
- •Participant is managed with a vitamin B6 dose of 15-30 mg/kg/day continuously beginning at < 3 months age, and willing to maintain this dose for the study duration.
- •Participants must have been offered dietary lysine restriction as adjunct therapy as part of standard clinical care.
- •Parent(s) or guardian(s) is willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures.
排除标准
- •Diagnosis is not confirmed: Participant does not have a mutation in the ALDH7A1 gene.
- •Participant was treated prenatally for PDE with pyridoxine (i.e. mother was on pyridoxine)
- •Timing of dietary restriction: Participant is on a lysine-restricted diet from an age > 3months.
- •Confounding factors:
- •Participant is a pre-term with a gestational age < 32 weeks
- •The participant has a birth weight less than the 2nd percentile or weighs less than 2nd percentile at study entrance (on age appropriate growth chart).
- •Participant shows an intracranial malformation or abnormality unrelated to ATQ deficiency, as diagnosed on the cranial ultrasound and/or MRI brain scan
- •Participant has any other disorder identified that can affect the cognitive function in the opinion of the coordinating principal investigators.
- •A known allergy or sensitivity to any component of the products commonly used in a lysine-restricted diet or to other products associated with lysine restriction or any other products associated with general study procedures.
- •Participant is on oral folinic acid and/or pyridoxal phosphate treatment at study entrance.
- •Participant has any condition or situation which, in the investigator's opinion, places the patient at significant risk of adverse events, or may interfere significantly with their participation and compliance in the study.
研究组 & 干预措施
Test Group
Patients receiving a lysine restricted diet adjunct to pyridoxine therapy will be considered as participants in the 'exposure'/test group
干预措施: Lysine Restricted Diet (Dietary Supplement)
Test Group
Patients receiving a lysine restricted diet adjunct to pyridoxine therapy will be considered as participants in the 'exposure'/test group
干预措施: Pyridoxine (Drug)
Control Group
Patients on pyridoxine mono-therapy will be participants in the 'control' group
干预措施: Pyridoxine (Drug)
结局指标
主要结局
Neurocognitive development at age 3 years
时间窗: 3 years
defined by total developmental index measured using the Bayley Scales for Infant and Toddler Development, 3rd Edition (Bayley-III)
Level of biochemical marker-α- aminoadipicsemialdehyde (AASA) in plasma and urine
时间窗: 3 years
次要结局
- Neurological deficits(3 years)
- Seizure frequency: clinical and electrical (EEG)(3 years)
- Quality of life(3 years)