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 correlate with observed performance and patient-reported fatigue.

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, clinically interpretable output bundle. If the two scores correlate moderately well, that would support convergent validity. 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 observational 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.
• Visit cadence: baseline and every 4 weeks for 12 weeks in the first phase.
• Optional extension: every 6 to 8 weeks afterward for longitudinal tracking.
• Primary endpoint: correlation between Energy Score and Measured Function Score at the same visit.
• Secondary endpoints: correlation between change scores, subgroup performance by mutation or phenotype class, and prediction of next-visit function from baseline Energy Score.

What Happens At Each Visit

• Run Mito Map 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.
• Calculate the Measured Function Score using the calculator page.
• Record any acute confounders such as illness, pain flare, unusual exertion, poor sleep, or medication changes.
• Repeat under the same testing conditions whenever possible.

How To Analyze It

• Cross-sectional analysis: Spearman or Pearson correlation between Energy Score and Measured Function Score at each visit and pooled across visits.
• Longitudinal analysis: mixed-effects models or repeated-measures correlation to test whether within-person changes track together over time.
• Calibration analysis: inspect whether Energy Score systematically overestimates or underestimates observed function in certain subgroups.
• Exploratory prediction: regress next-visit 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.
• 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 and easy to launch.
• Directly tests whether the model has real-world signal.
• 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