Global Prospective Natural History Study of POLG Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 27
- 主要终点
- Scale for the Assessment and Rating of Ataxia (SARA)
研究概览
简要总结
The PIONEER study is a prospective, natural history study dedicated to characterizing the clinical progression of POLG-related disorders. The research aims to bridge the gap between genetic diagnosis and drug development by mapping how these rare mitochondrial conditions evolve over time. By observing the disease's natural trajectory through a multi-center approach, The study identifies critical clinical milestones that serve as a foundation for evaluating therapeutic efficacy and future therapeutic interventions
详细描述
This is a multi-centre, Multi-country Prospective Observational Natural History study designed to bridge the gap between genetic diagnosis and therapeutic development for POLG-related disorders. These mitochondrial conditions are rare. This study utilizes a prospective, longitudinal design which allows researchers to track the "phenotypic evolution" of the disease over several years, providing the high-quality baseline data that regulatory agencies like the FDA require to evaluate the success of future drug interventions.
clinical parameters such as the Newcastle Mitochondrial Disease Scale (NMDAS) for multi-system involvement, the SARA scale for ataxia, and functional tests like the Nine-Hole Peg Test for motor dexterity, alongside fluid biomarkers including GDF-15 and FGF-21 are conducted to validate clinical endpoints throughout the study duration. inclusion criteria require participants of any age to have a genetically confirmed POLG-related disorder with documented pathogenic variants, as well as the ability to comply with longitudinal follow-up assessments over 3 years. This rigorous framework allows researchers to correlate specific genetic mutations with objective clinical milestones, providing the necessary baseline data to evaluate the efficacy of future therapeutic interventions.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male & female from age 0 to
- •A genetically confirmed POLG -associated disorder based on both phenotype and genotype is required.
- •Parental/guardian permission (informed consent) and if appropriate with child assent.
排除标准
- •Diagnosis of mitochondrial disorder other than POLG
- •Subject with POLG Variant of unknown significance or benign variant.
- •Parents/guardians or subjects who, in the opinion of the investigator, may be non-compliant with the study schedules or procedures.
- •Subjects unable or unwilling to provide informed consent.
- •History of or current clinically important condition other than what is related to the PMD which, in the opinion of the Investigator will confound the results of the NHS.
研究组 & 干预措施
Single Observational Cohort
Single Observational Cohort: Individuals (Pediatric and Adults) with genetically confirmed POLG-related disorders. No intervention is administered. Participants undergo longitudinal clinical assessments, patient-reported outcomes, biomarker collection, and review of routine clinical data.
结局指标
主要结局
Scale for the Assessment and Rating of Ataxia (SARA)
时间窗: Baseline through 36 months (every 12 months)
The Scale for the Assessment and Rating of Ataxia (SARA) is a clinical scale that is based on a semi-quantitative assessment of cerebellar ataxia on an impairment level. Total scores range from 0 to 40. Higher scores indicate greater ataxia severity.
次要结局
- Newcastle Mitochondrial Disease Scale(Baseline through 36 months (every 12 months))
- Newcastle Paediatric Mitochondrial Disease Scale (NPMDS)(Baseline through 36 months (every 12 months))
- Patient-Reported Outcomes Measurement Information System (PROMIS) Mitochondrial Fatigue(Baseline through 36 months (every 6 months))
- Research and Development 36 (RAND-36) Health Survey Quality of Life(Baseline through 36 months (every 12 months))
- Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale(Baseline through 36 months (every 12 months))
- Gastrointestinal Symptom Rating Scale (GSRS) Total Score(Baseline through 36 months (every 12 months))
- Paediatric (PedsQL) Gastrointestinal Symptoms Module(Baseline through 36 months (every 12 months))
- Quality of Life in Epilepsy Inventory-31-P (QOLIE-31-P)(the questionnaire shall be reassessed on Baseline visit, 6 months, every 12 months through 36 months.)
- Paediatric Quality of Life Inventory (PedsQL) Epilepsy Module(the questionnaire shall be reassessed on Baseline visit, 6 months, and every 12 months, through 36 months.)
- Patient Global Impression of Change (PGI-C)(Baseline through 36 months (baseline, 12 months))
- Overall Survival(Baseline through 36 months (at every visit))
- Number of DNA Polymerase Gamma (POLG) Disease-Related Hospitalizations(Baseline through 36 months (at every visit))
- DNA Polymerase Gamma (POLG) Burdensome Symptom Assessment(Baseline through 36 months (at every visit))