EndoSense: Continuous Real-Time Monitoring of Health Markers in Endocrine and Metabolic Disorders

EndoSense is a monocentric, single-arm, non-randomized, before-and-after interventional study conducted at the University Hospital Zurich within the European ENDOTRAIN consortium. The study is designed to evaluate whether continuous wearable monitoring, combined with dynamic hormone sampling, can capture meaningful physiological and endocrine responses during standardized environmental challenges in adults with endocrine or metabolic disorders.

Current diagnostic approaches in endocrinology often rely on single time-point measurements, although many endocrine and metabolic processes vary across the day and in response to salt intake, meals, fasting, sleep, and physical activity. EndoSense addresses this gap by combining home-based physiological monitoring with structured dietary and activity modules. The study will assess whether wearable-derived data can provide clinically relevant information on blood pressure, heart rate, heart rate variability, activity, sleep, temperature, and glucose patterns, and whether these data correspond to dynamic hormonal changes.

Each participant will complete a structured home-monitoring protocol. The protocol includes a baseline home-monitoring period followed by sequential dietary sodium modulation, starting with a low-sodium phase and followed by a high-sodium phase. Standardized mixed-meal, fasting, postural, and short exercise modules are included to characterize postprandial, fasting, hemodynamic, and stress-related physiological responses. These modules may be adapted or omitted according to the participant's underlying condition, safety considerations, and preferences after consultation with the study physician.

During the home-monitoring phase, participants will wear several study devices. These include devices for periodic blood pressure and pulse monitoring, continuous glucose monitoring, activity and movement assessment, sleep monitoring, and temperature monitoring. Data from these devices are collected for research purposes only and will not guide clinical care during the study. Participants will also complete brief electronic diaries and questionnaires to document adherence, symptoms, sleep, physical activity, usability, and acceptance of the study devices.

A subset of participants who provide separate consent will undergo dynamic hormone sampling using the U-RHYTHM system. This device collects subcutaneous interstitial fluid samples over approximately 27 hours and is used to study day-night and short-term hormone patterns. The hormone sampling module is optional and will be performed at selected time points during the protocol and, when appropriate, during routine clinical assessments.

After the home-based phase, participants will undergo a clinical integration phase during routine care at the Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich. Wearable data collected during routine diagnostic procedures will be compared with standard clinical assessments to explore how sensor-derived patterns relate to established endocrine and metabolic tests.

The study uses a within-participant design, meaning that each participant serves as their own reference across the different protocol phases. This design reduces between-person variability and allows the researchers to assess individual physiological responses to standardized changes in salt intake, meals, fasting, and short exercise. The study will also explore whether these responses differ across endocrine and metabolic conditions and whether biological sex influences physiological or hormonal patterns.

Safety measures are integrated throughout the protocol. Participants receive standardized instructions, predefined safety thresholds, and access to study physician contact if concerning symptoms or abnormal measurements occur. Potential risks include transient changes in blood pressure or glucose levels, discomfort related to dietary changes or exercise, and mild local reactions related to wearable devices or optional sampling procedures. Participation is voluntary, and participants may withdraw at any time without consequences for their clinical care.

The study aims to establish a sensor-integrated research framework for endocrine and metabolic disorders. In the long term, the knowledge generated by EndoSense may support the development of wearable-based monitoring environments as complementary tools for endocrine diagnostics, risk assessment, and personalized clinical care.

• Sequential Dietary Sodium Modulation (Behavioral), also known as Mixed-Meal and Fasting Challenge, Short Exercise and Postural Challenge, Diagnostic dynamic test: Participants will complete a standardized home and clinic monitoring protocol using wearable devices. The protocol includes low- and high-sodium diet phases, meal and fasting modules, postural and short exercise challenges, and wearable monitoring during routine endocrine functional tests. The study will assess changes in blood pressure, heart rate, glucose, activity, sleep, temperature, and hormone patterns in response to these challenges.

Primary outcomes

• Change in 24-hour systolic blood pressure [From Day 6 (end of low-sodium phase) to Day 13 (end of high-sodium phase)]: Change in mean 24-hour systolic blood pressure (mmHg), measured using a validated cuffless automated home blood pressure device, comparing the last 24 hours of the high-sodium diet phase to the last 24 hours of the low-sodium diet phase.

Secondary outcomes

• Change in 24-Hour Diastolic Blood Pressure [Day 6 to Day 13]: Change in mean 24-hour diastolic blood pressure (mmHg), measured via automated home blood pressure device.
• Change in Resting Heart Rate [Day 6 to Day 13]: Change in mean resting heart rate (beats per minute), measured via wearable actimeter/ECG device.
• Change in Heart Rate Variability [Day 6 to Day 13]: Change in heart rate variability (SDNN, milliseconds), measured via wearable ECG device.
• Change in Mean Interstitial Glucose Concentration [Day 6 to Day 13]: Change in mean interstitial glucose concentration (mmol/L), measured via continuous glucose monitor.
• Change in Percentage of Time in Target Glucose Range [Day 6 to Day 13]: Change in percentage of time with interstitial glucose within target range (%), measured via continuous glucose monitor.
• Change in Plasma Aldosterone Concentration [Day 6 to Day 13]: Change in aldosterone concentration (pg/mL), measured in interstitial microdialysate via the U-RHYTHM sampling device and quantified by LC-MS/MS.
• Change in Plasma Renin Concentration [Day 6 to Day 13]: Change in renin concentration (pg/mL), measured in interstitial microdialysate via the U-RHYTHM sampling device and quantified by ELISA.
• Change in Interstitial Cortisol Rhythm (Area Under the Curve) [27-hour U-RHYTHM sampling window at end of each phase (Day 6-7 vs. Day 13-14)]: Change in cortisol area-under-the-curve (nmol/L×h) over the 27-hour sampling window, measured via U-RHYTHM interstitial microdialysis and quantified by LC-MS/MS.
• 24-Hour Urinary Sodium Excretion [Day 7 and Day 14]: Sodium excretion (mmol/24h) in a 24-hour urine collection, used to verify dietary sodium adherence.
• Change in EQ-5D Visual Analog Scale Score [Day 1, Day 7 and Day 14]: Change in self-rated overall health, measured using the EQ-5D Visual Analog Scale (units on a 0-100 scale).
• Change in Pittsburgh Sleep Quality Index Global Score [Day 1, Day 7 and Day 14]: Change in sleep quality, measured using the Pittsburgh Sleep Quality Index (PSQI) global score (units on a 0-21 scale).
• System Usability Scale Score [Day 7 and Day 14]: Wearable device usability, measured using the System Usability Scale (SUS) (units on a 0-100 scale).
• International Physical Activity Questionnaire-Short Form Score [Day 1, Day 7 and Day 14]: Self-reported physical activity level, measured using the IPAQ-SF (MET-minutes/week).

Other outcomes

• Correlation Between Actigraphy-Derived Total Sleep Time and Diurnal Cortisol Rhythm [27-hour U-RHYTHM sampling window at end of each phase]: Spearman's correlation coefficient (rho) between total sleep time (hours; measured via Somnofy sleep monitor) and cortisol peak-to-nadir ratio (dimensionless; derived from U-RHYTHM interstitial sampling with LC-MS/MS).

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

Diagnosis or suspected diagnosis of at least one endocrine or metabolic disorder, including:

* Overweight or obesity, defined as body mass index of 25 kg/m² or higher
* Essential hypertension
* Diabetes mellitus, including type 1 diabetes, type 2 diabetes, gestational diabetes, maturity-onset diabetes of the young, or unclassified diabetes
* Hypoglycemia
* Endogenous hypercortisolism
* Primary aldosteronism
* Endogenous or exogenous adrenal insufficiency
* Congenital adrenal hyperplasia
* Polycystic ovary syndrome
* Adrenocortical tumor or adrenal incidentaloma
* Functional or non-functional pituitary tumor
* Pituitary insufficiency
* Polyuria-polydipsia syndrome
* Hyponatremia
* Functional or non-functional neuroendocrine tumor
* Osteoporosis
* Lipid disorder
* Thyroid disorder
* Hypoparathyroidism or hyperparathyroidism
* Inborn error of metabolism
* People undergoing gender-affirming hormone therapy

Exclusion Criteria:

* Known or suspected severe skin disorder or allergy that may interfere with wearable sensor placement, such as extensive eczema, psoriasis, chronic ulcers, or severe tape intolerance
* Known impaired wound healing or strong keloid tendency that would make repeated skin application or microneedle use unsuitable
* Pregnancy or lactation, for participation in home monitoring or dynamic hormone sampling
* Known or suspected bleeding disorder, such as von Willebrand disease
* Current treatment with anticoagulant or antiplatelet therapy at a dose that increases bleeding risk
* Severe acute or chronic medical condition that, in the investigator's opinion, would interfere with study procedures or compromise participant safety, such as decompensated heart failure, unstable angina, or acute systemic infection
* Current lithium treatment, because the intervention may alter lithium levels
* Recent travel across more than 4 time zones within the past 14 days, if study endpoints rely on circadian hormone profiles
* Ongoing shift work, if study endpoints rely on circadian hormone profiles
* Inability to give informed consent
* Inability to comply with study procedures

• Felix Beuschlein, Prof. Dr. med., Study chair, University Hospital, Zürich
• Thomas Uslar, MD; Assistant Professor, Study director, Pontificia Universidad Católica de Chile, CETREN-UC / University Hospital Zürich
• Felix Beuschlein, Prof. Dr. med., Principal investigator, University Hospital, Zürich

NIH grants: 2025