Fig 1.
ADVANTAGE Study Protocol Overview Across All Three Cohorts.
Comprehensive timeline showing assessment components and participant journey for Extreme Visceral Pain (high pain despite low disease activity), Lack of Visceral Pain (low pain despite high disease activity), and Healthy Controls cohorts. All participants complete baseline visit (~3 hours) with structured clinical interview, validated questionnaires (BPI-SF, McGill, disease-specific scales), quantitative sensory testing (QST: thermal, vibration, pressure pain thresholds), and ADVANTAGE Diary remote mobile app setup for daily pain ratings (0-10 Likert scale). Extreme Visceral Pain and Lack of Visceral Pain cohorts provide biological samples (50 mL blood for DNA/serum, urine, vaginal swabs, faeces). Extreme Visceral Pain and Healthy Controls proceed to 4-week wearable monitoring (chest-worn respiratory sensor, wrist-worn activity/HR sensor) followed by return visit (~1.5 hours) for repeat assessments, device return, and optional bio-sampling.
Table 1.
Inclusion and Exclusion Criteria for the Extreme Visceral Pain and Lack of Visceral Pain cohorts. Comprehensive eligibility matrix for the remote mobile app sub-study, wearable sensor sub-study, and bio-sampling sub-study. Common criteria: ≥ 18 years, UK-based, informed consent capable. Sub-study exclusions ensure safety (pacemakers, contact dermatitis), feasibility (travel restrictions), and cohort purity (no confounding pain conditions). Criteria support n = 350 total recruitment with n = 100 wearable sub-study power (80% power).
Table 2.
Inclusion and Exclusion Criteria for the Healthy Controls cohorts. Comprehensive eligibility matrix for the remote mobile app sub-study, and wearable sensor sub-study. Common criteria: ≥ 18 years, UK-based, informed consent capable. Sub-study exclusions ensure safety (pacemakers, contact dermatitis), feasibility (travel restrictions), and cohort purity (no pain conditions).
Fig 2.
Participant Recruitment and Cohort Assignment Flow Diagram.
Flowchart depicts screening, eligibility assessment, randomisation, and cohort assignment processes. NHS patient referrals and healthy volunteer recruitment pathways lead to initial screening using inclusion/exclusion criteria (Table 1). A six-week ADVANTAGE Diary remote mobile app phase determines cohort assignment: Extreme Visceral Pain (pain ≥4 on two occasions ≥1 week apart), Lack of Visceral Pain (pain <4 throughout), Healthy Controls (baseline only). Subsequent baseline/follow-up visits include optional wearable sub-study and bio-sampling as per eligibility. Decision points and participant progression shown chronologically.
Fig 3.
Wearable Sensor Deployment and Participant Instructions for the ADVANTAGE Study.
Chest-worn respiratory sensor and wrist-worn physiological monitor setup for 4-week continuous data collection from Extreme Visceral Pain and Healthy Controls cohorts. Diagram illustrates wireless charging station, 2-metre Discovery App tablet sync range for data upload, daily reapplication protocol (shower before reattachment, correct orientation), and smartphone app for ad libitum pain reporting (0-10 Likert scale). Key operational constraints shown: non-waterproof (daily removal for showering), medical imaging contraindication (X-ray/MRI interference), QR code access to instructional videos. Ensures compliance for primary endpoint analysis correlating respiration rate, HRV, activity, and posture against real-time pain scores.