PEARL - Pediatric Evaluation and Registry for Liver Cholestasis in Canada
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 13
- 主要终点
- PEARL Registry - Primary Outcome
研究概览
简要总结
The purpose of this study is to create a national, multi-centre registry for children with Alagille syndrome (ALGS) and Genetic Intrahepatic Cholestasis (GIC) that follows participants long-term, ensuring standardized, high-quality data capture across all participating pediatric hepatology centres.
Inclusion criteria:
• Pediatric participants (<18 years old) with genetically confirmed or clinically diagnosed ALGS or any of the various subtypes of GIC, each associated with a distinct genetic mutation: A. PFIC Type 1 (FIC1 Deficiency) - Mutation in ATP8B1 gene. B. PFIC Type 2 (BSEP Deficiency) - Mutation in ABCB11 gene. C. PFIC Type 3 (MDR3 Deficiency) - Mutation in ABCB4 gene. D. PFIC Type 4 (TJP2 Deficiency) - Mutation in TJP2 gene. E. PFIC Type 5 (FXR Deficiency) - Mutation in NR1H4 gene. F. PFIC Type 6 (MYO5B-Associated) - Mutation in MYO5B gene. G. Progressive cholestasis of northwestern Quebec (PCNQ)-Mutation in UTP4 gene.
- Enrollment within Canadian pediatric liver centers participating in the registry.
- Written informed consent obtained from participant if they have the capacity, or parents/guardians, and assent from participants as appropriate.
Exclusion criteria:
• Inability to comply with follow-up requirements (lost to follow-up). Participants will be recruited from our hepatology clinics retrospectively (diagnosed on or after January 1, 2022) and prospectively (newly diagnosed). Written consent/assent will be obtained from all participants prior to data collection from the participants' medical chart.
详细描述
Cholestatic liver diseases of genetic origin represent a major cause of chronic liver disease, morbidity, and liver transplantation in children. Among these, Alagille syndrome (ALGS) and the spectrum of disorders traditionally grouped as Progressive Familial Intrahepatic Cholestasis (PFIC) account for a substantial proportion of pediatric cholestasis worldwide. Advances in molecular genetics have demonstrated that PFIC represents only a subset of a broader and expanding group of monogenic disorders affecting bile formation, secretion, and transport. As such, the term Genetic Intrahepatic Cholestasis (GIC) has emerged as a more inclusive and biologically accurate classification, encompassing both classical PFIC disorders and genetically defined cholestatic conditions that do not fit existing PFIC subtypes.
Genetic Intrahepatic Cholestasis (GIC) refers to a heterogeneous group of inherited disorders characterized by impaired bile acid synthesis, transport, or canalicular excretion, leading to chronic intrahepatic cholestasis beginning in infancy or childhood. This category includes, but is not limited to, disorders caused by pathogenic variants in genes such as ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, MYO5B, and others, as well as newly described or ultra-rare conditions that are not yet formally classified. Importantly, the clinical course, treatment response, and long-term outcomes of GIC vary widely by genotype, underscoring the need for granular, longitudinal, genotype-phenotype-linked data. Alagille syndrome, a multisystem disorder most commonly caused by pathogenic variants in JAG1 or NOTCH2, represents a distinct but related cholestatic condition with significant variability in hepatic severity and outcomes. Despite overlapping therapeutic strategies with GIC particularly the increasing use of ileal bile acid transporter (IBAT) inhibitors. ALGS has unique clinical trajectories that warrant dedicated, disease-specific investigation within a unified registry framework.
The Canadian Pediatric Hepatology Research Group (CPHRG) is a national collaborative network comprising all academic pediatric hepatology centers across Canada. The group is dedicated to advancing research, improving clinical outcomes, and informing health policy for children with liver diseases through coordinated, multi-center initiatives. Despite this unified national infrastructure, Canada currently lacks a dedicated pediatric hepatology registry focused on genetic cholestatic disorders.
Participants will be recruited from our hepatology clinics retrospectively (diagnosed on or after January 1, 2022) and prospectively (newly diagnosed). Written consent/assent will be obtained from all participants prior to data collection from the participants' medical chart.
Methodology for Retrospective Participants
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pediatric participants (<18 years old) with genetically confirmed or clinically diagnosed ALGS or any of the various subtypes of GIC, each associated with a distinct genetic mutation:
- •A. PFIC Type 1 (FIC1 Deficiency) - Mutation in ATP8B1 gene. B. PFIC Type 2 (BSEP Deficiency) - Mutation in ABCB11 gene. C. PFIC Type 3 (MDR3 Deficiency) - Mutation in ABCB4 gene. D. PFIC Type 4 (TJP2 Deficiency) - Mutation in TJP2 gene. E. PFIC Type 5 (FXR Deficiency) - Mutation in NR1H4 gene. F. PFIC Type 6 (MYO5B-Associated) - Mutation in MYO5B gene. G. Progressive cholestasis of northwestern Quebec (PCNQ)-Mutation in UTP4 gene. Other novel PFIC-like conditions continue to be identified and may be included in the registry. If additional conditions are identified for inclusion in the registry, a protocol amendment will be submitted for REB approval.
- •Enrollment within Canadian pediatric liver centers participating in the registry. These include: Children's Hospital of Eastern Ontario (Ottawa, ON, Lead Site), CHU Sainte-Justine (Montreal, QC), McMaster Children's Hospital (Hamilton, ON), Montreal Children's Hospital (Montreal, QC), Alberta Children's Hospital (Calgary, AB), Stollery Children's Hospital (Edmonton, AB), Janeway Children's Health and Rehabilitation Centre (St. John's, NL), Jim Pattison Children's Hospital (Saskatoon, SK), Children's Hospital LHSC (London, ON), Children's Hospital IWK Health Centre (Halifax, NS), BC Children's Hospital (Vancouver, BC), HSC Winnipeg Children's Hospital (Winnipeg, MB), Hôpital de l'Enfant-Jésus (Quebec City, QC)
- •Written informed consent obtained from participant if they have the capacity, or parents/guardians, and assent from participants as appropriate.
排除标准
- •Inability to comply with follow-up requirements (lost to follow-up)
研究组 & 干预措施
PEARL Registry
genetically confirmed or clinically diagnosed ALGS or any of the various subtypes of GIC
结局指标
主要结局
PEARL Registry - Primary Outcome
时间窗: 2-5 years
To establish a national, multi-center, longitudinal registry for children with ALGS and GIC in Canada, incorporating both prospective enrollment and retrospective data collection, and ensuring standardized, high-quality data capture across participating pediatric hepatology centers.
次要结局
- PEARL Registry - Secondary Outcomes(2-5 years)
研究者
Mohit Kehar
Pediatric Gastroenterologist and Hepatologist
Children's Hospital of Eastern Ontario