Mito Map Correlation Trial

Scientific Rationale

The Energy Score is a mechanistic estimate built from age, mutation context, graph burden, phenotype burden, patient-state burden, interventions, and optionally labs. The Measured Function Score is an observed output score built from actual performance and symptom burden. In theory, if the mechanistic model is capturing real biologic reserve, it should rise and fall with observed performance and patient-reported fatigue inside the same individual, not just show a weak average association across different people.

This trial treats the Measured Function Score as a pragmatic external anchor. It is not a gold standard for mitochondrial function, but it is a low-cost, repeatable, home-friendly output bundle. If the two scores track moderately well within a person, that supports the idea that the model can be used for self-monitoring. If they also correlate across the cohort, that strengthens the broader validity claim. If they diverge, that tells you where the model may need recalibration or where observed function may be influenced by factors the graph does not yet capture.

Proposed Study Design

• Type: prospective remote longitudinal validation cohort.
• Population: adults with suspected mitochondrial dysfunction, mitochondrial disease, energy-limiting chronic symptoms, or mitochondrial-relevant phenotypes.
• Baseline data: age, sex, mutation view if known, patient states, phenotype burden, interventions, labs when available, Energy Score, and full Measured Function Score collected from home.
• Check-in cadence: baseline and every 2 to 4 weeks for 12 weeks in the first phase.
• Optional extension: monthly afterward for longer-term self-tracking.
• Primary endpoint: within-person association between Energy Score and Measured Function Score across repeated home check-ins.
• Secondary endpoints: population-level correlation at matched timepoints, subgroup performance by mutation or phenotype class, and prediction of next-check-in function from baseline Energy Score.

What Happens At Each Visit

• Run Mito Map from home with the current inputs and record the Energy Score.
• Collect grip strength, 5x sit-to-stand, chair-support level, and fatigue burden using the standardized protocol page in the same home setup whenever possible.
• Calculate the Measured Function Score using the calculator page.
• Record any acute confounders such as illness, pain flare, unusual exertion, poor sleep, menstrual cycle effects, travel, or medication changes.
• Repeat under the same conditions, same chair, and same device whenever possible.

How To Analyze It

• Primary longitudinal analysis: repeated-measures correlation, mixed-effects models, or simple within-person trend analyses to test whether changes in the two scores track together over time.
• Personal usability analysis: inspect whether each individual gets a stable and interpretable tracking signal rather than noisy week-to-week swings driven by measurement conditions.
• Population analysis: Spearman or Pearson correlation between Energy Score and Measured Function Score at matched check-ins and pooled across the cohort.
• Calibration analysis: inspect whether Energy Score systematically overestimates or underestimates observed home function in certain subgroups.
• Exploratory prediction: regress next-check-in Measured Function Score on baseline Energy Score, adjusting for age, sex, and baseline measured function.

Critique And Limitations

• No gold standard: neither score is a pure measure of mitochondrial ATP production, so the study tests convergence, not absolute truth.
• Circularity risk: if symptoms heavily influence both model inputs and measured fatigue, correlation could be inflated by shared symptom information.
• Home measurement noise: chair height, flooring, grip device quality, effort, timing, and household distractions can add extra variability.
• Functional confounders: orthopedic pain, deconditioning, neurologic disease, obesity, or motivation can affect measured performance independent of mitochondria.
• Model flexibility: if the Energy Score keeps changing during development, the study can become a moving target. Freeze a version before formal validation.
• Composite-score subjectivity: the Measured Function Score weights are still heuristic and should eventually be learned from data.
• Short follow-up: 12 weeks is enough for correlation and short-term tracking, but not enough to establish long-term prognostic validity.

Why This Trial Is Still Worth Doing

• Low cost, remote, and easy to launch.
• Directly tests whether the model has real-world signal in home use, not just in theory.
• Creates a practical self-tracking framework patients can repeat without traveling to a clinic.
• Creates the dataset you need to improve the calculator and the Energy Score later.
• Can be run before a larger interventional study.
• Gives a clean bridge between mechanistic biology and actual function.

Literature Basis

Frequently Asked Questions