Truway Whole-Body Digital Twin and Physiologic Resilience Study (TRU-OMNIBODY)

Prospective Development and External Validation of a Multimodal Whole-Body Digital Twin for Quantification of Cross-Organ Physiologic Reserve, Recovery Dynamics, and Emerging Health-State Change

TRU-OMNIBODY is a prospective observational study designed to develop and independently validate a research-only whole-body digital twin. The digital twin will combine measurements from multiple body systems to create a participant-specific representation of physiologic state, resilience, and recovery.

The study plans to enroll approximately 450 adults between 18 and 80 years of age. Participants will include generally healthy adults and adults with stable cardiometabolic, respiratory, or mobility-related conditions. Study measurements may include wearable-sensor data, heart rate and rhythm, blood pressure, oxygen saturation, autonomic responses, body composition, mobility, muscle function, sleep, activity, cognitive performance, point-of-care imaging, laboratory measurements, and optional biospecimens.

Participants will complete a standardized resilience assessment consisting of rest, active standing, a six-minute walk, a cognitive dual task, and monitored recovery. Selected measurements will also be collected during home monitoring and follow-up visits for up to 12 months.

The primary objective is to determine how accurately a locked digital-twin model predicts Whole-Body Recovery Burden, a research measure derived from the timing and magnitude of recovery across several physiologic systems. Model development and testing will be separated so that the final evaluation is performed in an independent validation cohort.

This study does not assign participants to a medical treatment. Digital-twin outputs will not be used to diagnose disease, recommend treatment, or replace evaluation by a qualified health care professional.

Human physiologic resilience depends on coordinated responses across the cardiovascular, respiratory, autonomic, metabolic, musculoskeletal, sensory, immune, behavioral, and environmental domains. Conventional clinical measurements generally evaluate these systems separately and at isolated points in time. TRU-OMNIBODY will investigate whether multimodal longitudinal measurements can be integrated into a participant-specific digital twin that represents whole-body physiologic reserve and recovery dynamics.

The study is designed as a prospective observational development-and-external-validation cohort. Approximately 450 adults aged 18 through 80 years will be enrolled across three planned cohorts: a reference-health cohort, a stable cardiometabolic cohort, and a stable respiratory or mobility-related cohort. Approximately 300 participants will contribute to model development, internal resampling, and model selection. Approximately 150 participants will be reserved for independent external validation. Validation data will remain separated from model-development activities until the digital-twin model, preprocessing procedures, model parameters, missing-data rules, and evaluation methods have been locked.

The whole-body measurement architecture may include continuous or episodic wearable-sensor measurements, electrocardiography, heart rate, blood pressure, pulse oximetry, respiratory measurements, autonomic testing, body composition, mobility and gait measurements, muscle strength, balance, sleep, physical activity, cognitive performance, point-of-care imaging, standard laboratory measurements, and optional biospecimen or multiomic assessments. Device identity, firmware, measurement quality, timing, and data provenance will be recorded when applicable.

At baseline, participants will complete a standardized resilience challenge. The planned sequence includes a resting stabilization period, transition from a monitored resting position to standing, a functional walking assessment, a validated cognitive dual task, and monitored recovery. Measurements collected before, during, and after the challenge will be used to characterize the magnitude, timing, coordination, and completeness of recovery across physiologic domains. A subset of participants may repeat the assessment within approximately 7 to 14 days to evaluate test-retest reliability.

Participants may also complete scheduled home monitoring, symptom and activity reporting, quarterly assessments, and final follow-up for up to 12 months. Longitudinal data will be used to establish participant-specific baselines, quantify within-person variation, and examine whether persistent deviations from personal baseline are associated with subsequently adjudicated health events or clinically meaningful changes. Health events will be evaluated according to prespecified adjudication procedures rather than inferred solely from digital-twin output.

The primary analysis will evaluate prediction error for Whole-Body Recovery Burden in the independent validation cohort. Whole-Body Recovery Burden is a prespecified research outcome representing integrated recovery delay or incomplete recovery across measured physiologic domains. The primary performance measure will compare the locked model prediction with the observed outcome following the standardized challenge. Secondary analyses will evaluate reliability, calibration, discrimination, uncertainty, missingness, domain-specific recovery, participant burden, protocol feasibility, and performance across demographic and clinical subgroups.

Exploratory analyses will evaluate cross-organ coupling, multimodal recovery phenotypes, individual resilience trajectories, change-point patterns, and the relationship between deviations from personal baseline and adjudicated health-state changes. Participant-level uncertainty estimates or abstention rules will be used when input quality is inadequate or measurements fall outside the model's supported range.

TRU-OMNIBODY is observational and does not assign a drug, biologic, device treatment, or therapeutic strategy. Investigational digital-twin outputs will remain separated from routine clinical decision-making and will not independently diagnose disease, recommend treatment, or direct participant care. Clinically significant observations obtained through validated conventional measurements will be managed according to the approved protocol, safety procedures, informed-consent document, and site-specific clinical escalation plan.

Inclusion Criteria:

• Age 18 through 80 years at enrollment.

• Able and willing to provide written informed consent.

• Able to understand study instructions and comply with protocol assessments.

• Able to complete the standardized physiologic resilience challenge safely, with a customary assistive device or protocol-permitted accommodation when needed.

• Clinically stable at screening, with no significant acute change in health status or prescribed medication regimen during the preceding 30 days, unless determined by the investigator not to affect participant safety or study measurements.

• Willing to undergo multimodal physiologic monitoring and use study-provided or compatible wearable equipment.

• Meets the criteria for one of the following prespecified cohorts:

  1. Reference Health Cohort: Generally healthy adult without an unstable or clinically significant condition expected to prevent safe completion of the protocol or materially impair interpretation of the reference measurements.
  2. Stable Cardiometabolic Cohort: Adult with one or more stable cardiometabolic conditions or risk factors, which may include controlled hypertension, dyslipidemia, obesity, prediabetes, or stable type 2 diabetes, without recent acute cardiometabolic decompensation.
  3. Stable Respiratory or Mobility Cohort: Adult with a stable chronic respiratory condition or mobility-related functional limitation, without a recent exacerbation, acute injury, or acute functional decline that would make protocol assessments unsafe.

• Participants meeting criteria for more than one clinical cohort will be assigned according to the prespecified cohort-classification hierarchy.

• Participation in optional biospecimen collection requires separate consent; declining optional biospecimen collection will not otherwise exclude an eligible participant.

Exclusion Criteria:

• Inability or unwillingness to provide informed consent.
• Acute illness, febrile illness, or suspected communicable infection at the time of assessment.
• Hospitalization, major surgery, or clinically significant acute medical event within 30 days before enrollment, unless reviewed and cleared by the investigator.
• Unstable cardiovascular disease, including recent acute coronary syndrome, decompensated heart failure, uncontrolled clinically significant arrhythmia, or symptomatic severe valvular disease.
• Acute respiratory exacerbation, unstable oxygen requirement, or resting respiratory status that the investigator determines would make the challenge unsafe.
• Resting blood pressure, heart rate, oxygen saturation, or other screening measurement outside the protocol-defined safety limits after repeat assessment.
• Recent syncope, recurrent unexplained falls, acute musculoskeletal injury, or another condition that would prevent safe standing, walking, or recovery monitoring.
• Neurologic, cognitive, psychiatric, visual, hearing, or communication impairment that would prevent informed consent or reliable completion of study procedures despite reasonable accommodation.
• Known intolerance to required wearable sensors, electrodes, adhesives, or monitoring procedures that cannot be addressed using an approved alternative.
• Participation in another clinical study or exposure to an investigational intervention that, in the investigator's judgment, could confound study measurements or increase risk.
• Any medical, functional, or behavioral condition that the investigator or designated medical monitor determines would create an unacceptable risk or compromise the scientific validity of the collected data.