An observational study in PolG, Primary Mitochondrial Myopathy, sponsored by The POLG Foundation. Recruiting at 21 sites in 9 countries. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by The POLG Foundation · Observational
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
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.
1,848 studies on the registry are indexed under Epilepsy; 422 are open to participants now.
This study's planned enrollment of 300 is above the median of 112 across 540 observational studies indexed under Epilepsy.
Browse Epilepsy studies →This is the only study on the registry with The POLG Foundation as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Target Population: Patients of all ages with genetically confirmed POLG disease (autosomal recessive or dominant).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Scale for the Assessment and Rating of Ataxia (SARA)
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.
Time frame: Baseline through 36 months (every 12 months)
Newcastle Mitochondrial Disease Scale
The Newcastle Mitochondrial Disease Adult Scale (NMDAS) is a validated, semi-quantitative clinical scoring instrument used to assess disease severity and progression in adults with mitochondrial disease. Total scores range from 0 to 145, with higher scores indicating greater disease severity and functional impairment. The NMDAS will be administered to participants aged 18 years and older.
Time frame: Baseline through 36 months (every 12 months)
Newcastle Paediatric Mitochondrial Disease Scale (NPMDS)
The Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) is a validated, semi-quantitative clinical scoring instrument used to assess disease severity and progression in paediatric patients with mitochondrial disease. Scores range from 0 to 82. Higher scores indicate greater disease severity and functional impairment. The NPMDS will be administered to participants aged 0-17 years.
Time frame: Baseline through 36 months (every 12 months)
Patient-Reported Outcomes Measurement Information System (PROMIS) Mitochondrial Fatigue
The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue instruments assess the impact and severity of fatigue. Age-appropriate PROMIS Fatigue instruments will be administered to participants and caregivers, as applicable. Scores are reported as standardized T-scores, typically ranging from approximately 20 to 80, with a population mean of 50 and standard deviation of 10. Higher scores indicate greater fatigue severity and worse fatigue-related burden.
Time frame: Baseline through 36 months (every 6 months)
Research and Development 36 (RAND-36) Health Survey Quality of Life
The RAND-36 Health Survey is a self-reported measure of health-related quality of life across eight health domains. This questionnaire will be used in adult patients age 18 and older. Domain scores range from 0 to 100. Higher scores indicate better health-related quality of life.
Time frame: Baseline through 36 months (every 12 months)
Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale
The Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale assesses health-related quality of life in pediatric participants using age-appropriate self-report and parent-proxy forms. Scores range from 0 to 100. Higher scores indicate better health-related quality of life.
Time frame: Baseline through 36 months (every 12 months)
Gastrointestinal Symptom Rating Scale (GSRS) Total Score
The Gastrointestinal Symptom Rating Scale (GSRS) assesses gastrointestinal symptom severity like reflux, abdominal pain, indigestion, diarrhoea, and constipation. The Total scores range from 1 to 7. Higher scores indicate more severe gastrointestinal symptoms and worse gastrointestinal health.
Time frame: Baseline through 36 months (every 12 months)
Paediatric (PedsQL) Gastrointestinal Symptoms Module
The Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module assesses gastrointestinal symptom-related quality of life in pediatric participants. Scores range from 0 to 100, with higher scores indicating better gastrointestinal health-related quality of life.
Time frame: Baseline through 36 months (every 12 months)
Quality of Life in Epilepsy Inventory-31-P (QOLIE-31-P)
The Quality of Life in Epilepsy Inventory-31-P (QOLIE-31-P) assesses epilepsy-specific quality of life in adults. Scores range from 0 to 100, with higher scores indicating better quality of life.
Time frame: 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 Paediatric Quality of Life Inventory (PedsQL) Epilepsy Module assesses epilepsy-related quality of life in pediatric participants using age-appropriate self-report and parent-proxy forms. Scores range from 0 to 100, with higher scores indicating better epilepsy-related quality of life.
Time frame: the questionnaire shall be reassessed on Baseline visit, 6 months, and every 12 months, through 36 months.
Patient Global Impression of Change (PGI-C)
The Patient Global Impression of Change (PGI-C) is a participant-reported assessment of overall change in health status since study enrolment. Scores range from 1 to 7, where 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse. Lower scores indicate improvement and higher scores indicate worsening.
Time frame: Baseline through 36 months (baseline, 12 months)
Overall Survival
Time from enrolment to death from any cause.
Time frame: Baseline through 36 months (at every visit)
Number of DNA Polymerase Gamma (POLG) Disease-Related Hospitalizations
Number of hospital admissions attributable to DNA Polymerase Gamma (POLG)-related disease complications during study follow-up.
Time frame: Baseline through 36 months (at every visit)
DNA Polymerase Gamma (POLG) Burdensome Symptom Assessment
The DNA Polymerase Gamma (POLG) Burdensome Symptom Assessment is a participant- or caregiver-reported assessment designed to identify the symptom related to DNA Polymerase Gamma (POLG)-related disease that has the greatest impact on daily life. Participants identify their most burdensome symptom and rate its severity and burden using an 11-point numeric rating scale ranging from 0 to 10, where 0 indicates "Not Present" and 10 indicates "Worst Imaginable". Higher scores indicate greater symptom burden and worse disease impact.
Time frame: Baseline through 36 months (at every visit)
Plan to share: No — The Clinical Study Report may be shared after study completion.
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