Natural History Study of Mitochondrial Myopathy

Muscle Strength of MM-COAST

Time frame: through study completion, an average of 5 years

Muscle strength will be measured longitudinally by handheld dynamometry strength assessments to confirm muscle weakness in proximal and distal muscle groups.

Balance of the MM-COAST

Time frame: through study completion, an average of 5 years

Balance will be measured by: (1) Standing tandem with eyes closed, (2) Standing tandem with eyes open, and (3) Single leg stand with eyes closed tests.

Dexterity of the MM-COAST

Time frame: through study completion, an average of 5 years

Dexterity will be measured by 9 Hole Peg Test (9HPT) and Functional Dexterity Test (FDT).

Mitochondrial Disease Burden for Adults

Time frame: through study completion, an average of 5 years

All subjects will complete the 'gold standard' Newcastle Scale of disease burden. Newcastle Adult Scale (NMDAS): Each question in the NMDAS has a possible score from 0-5. Each of the first 3 section scores are calculated by simply summing the scores obtained for each question in that section. The higher the score the more severe the disease. The quality of life section has separate scoring.

Mitochondrial Disease Burden for Children

Time frame: through study completion, an average of 5 years

All subjects and their parents will complete the 'gold standard' Newcastle Scale of disease burden. Newcastle Pediatric Scale (NPMDS): NPMDS is scored by section and the final (total) score is the sum of all section scores. The section scores vary by age group (0-24 months, 2-11 years, and 12-18 years). Maximum possible total NPMDS scores are 95 for subjects under 24 months of age and 107 for those between two and 18 years of age. Higher scores indicate worse conditions.

Challenges in Activities of Daily Life (ADLs)

Time frame: through study completion, an average of 5 years

All subjects and their parents will complete the Karnofsky-Lansky score to assess functional abilities at each visit. Karnofsky Lansky Scale: 0-100. 0-40: Unable to care for self, requires equivalent of institutional or hospital care; disease may be progressing rapidly. 50-70: Unable to work; able to live at home and care for most personal needs; varying amount of assistance needed. 80-100: Able to carry on normal activity and to work; no special care needed.

Functional Tasks of the Mitochondrial Myopathy Functional Scale (MMFS)

Time frame: through study completion, an average of 5 years

The MMFS (In Person and Telemedicine Versions) will be used to quantify motor performance in NUBPL-disease in abilities to complete functional tasks such as standing, walking and gait. MMFS data will be correlated using Pearson correlation coefficient to Newcastle and Karnofsky scores, and objective measures to assess for clinical meaning. MMFS Scale: 3: Able (fully meets criteria); 2: Moderately Able (partially meets, some compensation needed); 1: Minimally Able (significant compensation needed); 0: Unable MMFS Totals: In-person Version: Total score: \*/ 66 (max score), Telemedicine Version: Total score: \*/54 (max score)

Clinical Progression: Survival

Time frame: through study completion, an average of 5 years

Patients will be marked as either "alive" or "deceased" at the time of a given visit date.

Clinical Progression: Growth

Time frame: through study completion, an average of 5 years

Patients will have their vitals recorded at the date of visit to obtain BMI (Kg/m\^2)) measurement, Height (m) and weight (kg) are required to calculate BMI.

Clinical Progression: Other Illnesses

Time frame: through study completion, an average of 5 years

Patients will have other illnesses not related to their mitochondrial disease recorded along with date of diagnosis and stability.

Clinical Progression: Hospitalizations

Time frame: through study completion, an average of 5 years

Patients will have prior hospitalizations counted and recorded. Any hospitalizations occurring within a year from the visit date will have specific information recorded including the dates of admission and discharge, and the reasons for admission and discharge.

Clinical Progression: Ambulatory Status

Time frame: through study completion, an average of 5 years

Patients will have their ambulatory status assessed by recording whether or not they can take 5 steps on their own. Patients' use of different kinds of wheelchairs will be recorded (manual, power assist, or power wheelchair or scooter) along with whether they are able to ambulate in the community or only in the household.

Clinical Progression: Pacemaker Requirement

Time frame: through study completion, an average of 5 years

As part of a patient's cardiopulmonary exercise test (CPET), pacemaker status will be assessed, and if a patient utilizes a pacemaker, it's make, model, and settings will be recorded.

Clinical Progression: Ventilatory Support

Time frame: through study completion, an average of 5 years

As part of a patient's respiratory history, ventilatory support status will be assessed by recording whether a patient uses the any of the following respiratory equipment: cough assist device, non-invasive ventilation including continuous positive airway pressure (CPAP) and Bi-pap, chest percussion, suctioning devices, other ventilation devices.

Clinical Progression: Gastrostomy Status

Time frame: through study completion, an average of 5 years

As part of a patient's nutritional assessment, a patient's gastrostomy status will be assessed by determining whether a patient utilizes a gastrostomy tube (or g-tube), when they had their g-tube placed and why, and whether it resulted in weight gain.

Qualitative Interviews

Time frame: through study completion, an average of 5 years

In-depth qualitative interviews to assess their perspective of meaningful change of individual domain assessments of the MM-COAST and MM-Function Scale.

MM patient-reported outcome measure (PROM), MM-IMPACT

Time frame: through study completion, an average of 5 years

Preliminary MM-IMPACT PROM, a multi-item scale which currently consists of 45 questions

What is a clinical trial?

A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.

Is it safe to participate?

Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.

Will I be compensated?

Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.

Will I receive a placebo instead of treatment?

When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.

Can I leave a trial if I change my mind?

Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.

How long does a clinical trial last?

Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.