Effectiveness of RMSSD-Based Adaptive Music Therapy (Skitii) in Reducing Treatment-Related Anxiety in Head and Neck Cancer Patients: Protocol for a Randomized Controlled Trial
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Background
Head and neck cancer (HNC) patients experience clinically significant anxiety in 65-85% of cases during active treatment. Anxiety is associated with treatment dropout rates reaching 26% in some cohorts, with each discontinuation resulting in suboptimal outcomes and estimated losses of INR 4-5 lakh per patient. Current supportive care lacks personalized, real-time non-pharmacological interventions. Skitii is an investigational medical device (CDSCO Class B, Licence SW/MD/MD13/2026/000003509) that uses continuous RMSSD monitoring via Polar H10 chest sensor to select music in real-time, targeting parasympathetic recovery (RMSSD >=30ms).
Methods
Prospective, open-label, randomized controlled superiority trial (1:1 allocation) at Yenepoya Medical College Hospital, Mangalore, India. Adults aged 18-75 years with confirmed HNC (any subsite, Stage I-IV) undergoing curative-intent radiotherapy and/or chemotherapy with baseline anxiety (HADS-A >=8 and <=18) will be enrolled. Participants are randomized to Skitii adaptive music therapy (30-minute sessions, 3 times daily, 4 weeks) or static music therapy control. Skitii employs a two-phase algorithm: Phase 1 (0-2.5 minutes) uses heart rate as a stress proxy; Phase 2 (2.5-20 minutes) uses RMSSD to adapt music every 2.5 minutes when physiological state changes by >=20%, targeting RMSSD >=30ms. Primary endpoint: HADS-A score change from baseline to Week 4. Secondary endpoints: treatment dropout rate, resting RMSSD, HADS-Depression, EORTC QLQ-C30, GAD-7, PHQ-9 and device validation (ICC >=0.90 vs Kubios HRV Standard). Sample size: 70 (35 per arm), powered at 80% to detect a 2.5-point HADS difference (SD=3.8, alpha=0.05, 15% dropout). Analysis: ANCOVA, intent-to-treat.
Discussion
This is the first randomized controlled trial evaluating RMSSD-based adaptive music therapy in cancer patients, and the first clinical investigation of Skitii as a CDSCO-registered investigational medical device. The active control design (static music therapy) isolates the specific effect of the adaptive algorithm from music exposure alone. A mandatory device validation sub-study with 15 healthy volunteers precedes patient enrollment. If positive, results will support CDSCO Class B device certification, future CE Mark (EU MDR 2017/745), and FDA De Novo clearance applications.
Trial Registration
Clinical Trials Registry - India: CTRI/2025/11/116732, registered November 2025.
