Definitive Randomized Controlled Trial Protocol for the Internal Nasal Valves (INVals) Method for Prevention of Respiratory Tract Infections and Nasal Allergies v1

A Prospective, Multicenter, Randomized, Controlled, Assessor-Blinded, 52-Week Clinical Trial 1. PROTOCOL SYNOPSIS This protocol describes a definitive randomized controlled trial designed to determine whether regular performance of the Internal Nasal Valves (INVals) Method, when added to usual respiratory-infection preventive practices, reduces the incidence of laboratory-confirmed symptomatic respiratory tract infections compared with usual preventive practices alone. The INVals Method is a non-pharmacological behavioral maneuver involving deliberate nasal inspiration through the internal nasal valve region, which are the narrowest part of the nasal cavities and using the Bernoulli’s Principle create the Venturi Effect thus potentially capable of influencing upper airway secretions movement [1]. The method and its originating hypothesis were described by Varma in a peer-reviewed publication [1]. The originating observations were based substantially on prolonged self-experimentation and prospective personal self-experimentation. They should therefore be regarded as hypothesis- generating rather than evidence establishing clinical efficacy. The purpose of this trial is to subject the hypothesis to independent, prospective, randomized, controlled evaluation. The trial is designed according to contemporary principles reflected in SPIRIT 2025 and TIDieR recommendations for transparent and reproducible intervention research [2–4]. 3. BACKGROUND Respiratory tract infections remain an important source of morbidity, mortality, healthcare utilization, work loss, and societal burden. The upper respiratory tract is not simply a conduit for inspired air. It is an important component of host defense. Airway mucus traps inhaled particles and microorganisms, while mucociliary transport facilitates their movement and clearance. Nasal epithelial barriers, innate immune mechanisms, antimicrobial molecules, microbiomes, and adaptive mucosal responses contribute to defense against respiratory pathogens [5–9]. Impairment of mucociliary clearance is associated with respiratory disease and susceptibility to infection [5–9]. These physiological mechanisms are well established. What remains unestablished is whether deliberately modifying nasal airflow through the internal nasal valves can augment these processes sufficiently to produce clinically meaningful protection from respiratory infections. 4. ORIGIN AND SCIENTIFIC RATIONALE OF THE INVals METHOD The INVals Method originated from long-term self-experimentation beginning in 1979 and was subsequently described in the related peer-reviewed publication [1]. The proposed mechanism invokes airflow through the relatively narrow internal nasal valve region. Deliberate brisk nasal inspiration across this narrow region of the internal nasal valves increases airflow velocity using the Bernoulli’s Principle, creating the Venturi Effect, and produces associated pressure changes consistent with principles of fluid dynamics [1]. These airflow and pressure changes may influence the movement of secretions within portions of the upper respiratory system. Airway mucus, mucociliary transport, epithelial defense, and mucosal immunity are independently established components of respiratory host defense [5–9]. 5. STUDY OBJECTIVE Primary Objective To determine whether daily performance of the INVals Method, in addition to usual respiratory- infection preventive practices, reduces the incidence of laboratory-confirmed symptomatic acute respiratory tract infection during 52 weeks compared with usual preventive practices alone. Secondary Objectives To determine whether the INVals Method affects: 1. total number of laboratory-confirmed respiratory infections; 2. incidence of asymptomatic laboratory-confirmed infection; 3. time to first respiratory infection; 4. pathogen-specific infection rates; 5. duration of respiratory illness; 6. symptom severity; 7. cumulative symptom-days; 8. fever-days; 9. activity-loss days; 10. work absenteeism; 11. healthcare utilization; 12. antibiotic use; 13. antiviral use; 14. hospitalization; 15. intervention adherence; 16. intervention fidelity; 17. participant acceptability; 18. adverse events. 6. HYPOTHESIS The primary hypothesis is that participants randomized to the INVals Method will experience a lower incidence of laboratory-confirmed symptomatic acute respiratory tract infections during 52 weeks than participants randomized to usual preventive practices alone. The study will maintain clinical and scientific equipoise.