PolG, Primary Mitochondrial Myopathy
Conditions
Keywords
POLG, POLG disease, Primary Mitochondrial Disease, Mitochondrial DNA Depletion Syndrome, Fibroblast Growth Factor 21 (FGF21), Growth Differentiation Factor 15 (GDF15), Epilepsy, Seizures, Ataxia, Progressive External Ophthalmoplegia, Neuropathy, Mitochondrial Myopathy, Natural History Study
Brief summary
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
Detailed description
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.
Interventions
None listed
Sponsors
The POLG Foundation
Jeeva Clinical Trials Inc
ClinTrek Research Private Limited
United Mitochondrial Disease Foundation (UMDF)
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* male \& female from age 0 to 75. * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Scale for the Assessment and Rating of Ataxia (SARA) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Newcastle Mitochondrial Disease Scale | Baseline through 36 months (every 12 months) | 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. |
| Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) | Baseline through 36 months (every 12 months) | 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. |
| Patient-Reported Outcomes Measurement Information System (PROMIS) Mitochondrial Fatigue | Baseline through 36 months (every 6 months) | 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. |
| Research and Development 36 (RAND-36) Health Survey Quality of Life | Baseline through 36 months (every 12 months) | 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. |
| Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale | Baseline through 36 months (every 12 months) | 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. |
| Gastrointestinal Symptom Rating Scale (GSRS) Total Score | Baseline through 36 months (every 12 months) | 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. |
| Paediatric (PedsQL) Gastrointestinal Symptoms Module | Baseline through 36 months (every 12 months) | 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. |
| 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. | 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. |
| 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. | 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. |
| Patient Global Impression of Change (PGI-C) | Baseline through 36 months (baseline, 12 months) | 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. |
| Overall Survival | Baseline through 36 months (at every visit) | Time from enrolment to death from any cause. |
| Number of DNA Polymerase Gamma (POLG) Disease-Related Hospitalizations | Baseline through 36 months (at every visit) | Number of hospital admissions attributable to DNA Polymerase Gamma (POLG)-related disease complications during study follow-up. |
| DNA Polymerase Gamma (POLG) Burdensome Symptom Assessment | Baseline through 36 months (at every visit) | 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. |
Countries
Australia, Denmark, Finland, Netherlands, Norway, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTPIONEER
PRINCIPAL_INVESTIGATORAmel Kaara
Harvard Medical School & Massachusetts General Hospital
PRINCIPAL_INVESTIGATOROmar Hikmat
Haukeland University / Bergen University
Outcome results
None listed