The Precision Mito- Mito Map COMPASS Study

COMPASS is a prospective, remote, longitudinal observational cohort study designed to externally evaluate the measurement behavior and longitudinal criterion validity of the frozen canonical Mito Map Energy Score. Participants complete seven matched assessments from baseline through week 12. The primary objective is to estimate the average within-person association between changes in the Energy Score and changes in a separately constructed objective home-function anchor based on protocolized grip-strength and five-times sit-to-stand measurements. The primary anchor excludes fatigue and shares no inputs with the Energy Score. The initial enrollment target is 400 adults across seven prespecified cohorts: healthy comparison; broad mitochondrial disease; POLG-related disease; post-infectious or autonomic illness; cancer and cancer survivorship; other persistent energy-limiting conditions; and Lyme disease or post-treatment Lyme disease syndrome. Participants meeting the dedicated POLG cohort definition are assigned to that cohort rather than the broad mitochondrial cohort. The 50-person POLG cohort is prespecified for descriptive and exploratory subgroup analyses and is not separately powered for confirmatory POLG-specific, variant-level, prognostic, or treatment-response claims. Secondary objectives include characterizing between-person association, test-retest reliability, adherence, missingness, assessment failures, participant burden, and safety during home measurement. Exploratory analyses will examine prediction of the next functional assessment, longitudinal transition yield, naturally occurring exposure changes, optional wearable measures, optional Flic symptom, context, and confirmed intervention markers, and variation across the seven cohorts. Cohort comparisons are exploratory and are intended to help distinguish shared and condition-specific patterns across complex energy-limiting illnesses. The study is non-interventional. It does not assign medications, supplements, devices, exercise, diet, or other treatment. Results will not establish diagnosis, treatment efficacy, clinical utility, prognosis, mitochondrial ATP production, or a minimum clinically important difference. The same dataset will not be used both to tune the Energy Score or functional anchor and to claim locked external validation.