This study will use a prospective, randomized, double-blind, controlled trial design to evaluate the efficacy and mechanisms of taVNS in promoting recovery in patients with PSD. After written informed consent is obtained from participants and their guardians, baseline demographic and clinical characteristics—including vital signs, neurological history, surgical and medication records, and electrocardiograms—will be collected in accordance with the trial’s inclusion and exclusion criteria.
Swallowing function will be evaluated using a combination of instrumental and clinical scales: the Penetration-Aspiration Scale (PAS), Fiberoptic Endoscopic Evaluation of Swallowing (FEES), Yale Pharyngeal Residual Severity Rating Scale (YPR-SRS), Modified Mann Assessment of Swallowing Ability (MASA), and the Chinese version of the Functional Oral Intake Scale (FOIS). Hyoid bone displacement and hyoid-thyroid approximation distance during volitional swallowing will be quantified using B-mode ultrasonography. Furthermore, motor-evoked potentials (MEPs) of the suprahyoid muscles will be recorded using a transcranial magnetic stimulator equipped with an MEP detection module (TMS-MEP).
Participants will be randomly assigned to either a taVNS group or a sham taVNS group, with 20 participants in each group. All participants will receive conventional swallowing rehabilitation in addition to their assigned stimulation intervention. Vital signs will be monitored after each session, and any adverse events (AEs) will be recorded. The FOIS will be reassessed at the 1-month follow-up. The trial flowchart is shown in
Study flow diagram. After screening and enrollment, 40 participants will be randomized 1:1 to receive either taVNS plus standard rehabilitation or sham taVNS plus standard rehabilitation. Outcomes will be assessed at baseline (day 0), postintervention (day 14), and follow-up (day 44). FOIS: Functional Oral Intake Scale; PAS: Penetration-Aspiration Scale; taVNS: transcutaneous auricular vagus nerve stimulation.
This study aims to evaluate the clinical efficacy of taVNS in treating PSD and to investigate the underlying mechanisms by which taVNS improves swallowing function.
Eligible participants will be recruited from the Acupuncture and Rehabilitation Department of Guangdong Second Hospital of Traditional Chinese Medicine. All participants must have a clinical and imaging-confirmed diagnosis of PSD and provide written informed consent prior to enrollment. The detailed inclusion and exclusion criteria are presented in
Participants aged 18-70 years, regardless of gender
A score of 11.3 on the Kubota Water Swallowing Test or impaired swallowing safety as assessed by the Volume‑Viscosity Swallow Test—Chinese Version
Duration of dysphagia between 2 wk and 6 mo
Relatively stable medication regimen for at least 1 week prior to enrollment
Signed informed consent
Patients with unstable vital signs or with active cerebral hemorrhage
Documented cardiac arrhythmia or baseline heart rate <60 beats/min
Presence of implantable medical devices, such as cardiac pacemakers, intracranial metallic implants, or cochlear implants
Local contraindications to electrical stimulation, including active external ear infection, dermatological lesions, or structural malformations
History of vagus nerve surgery or traumatic injury
Dysphagia attributable to nonstroke etiologies
Significant cognitive impairment or consciousness disorders that may compromise assessment compliance
Elimination criteria included poor compliance and unwillingness to cooperate with outcome assessment, or poor compliance and a refusal to cooperate with the implementation of interventions.
Dropout criteria included poor adherence to the study protocol, specifically refusal to cooperate with outcome assessments, or unwillingness to comply with the assigned intervention regimen.
Discontinuation criteria included the occurrence of severe complications or an active systemic infection during the trial period, or the emergence of severe allergic reactions or other serious AEs attributable to the intervention.
Prior to study initiation, all patients will receive a comprehensive explanation of the trial procedures, including expected time commitment, potential benefits, and foreseeable risks. Written informed consent will be obtained from each participant prior to enrollment. A total of 40 randomization cards indicating group assignment will be prepared in advance according to a computer-generated randomization sequence. Each card will be sealed inside an opaque envelope of uniform size and color. These envelopes will be securely stored and managed by an independent member of the research team who is not involved in patient recruitment or outcome assessment. As eligible participants are enrolled, a designated study specialist will open the envelopes sequentially in the order of enrollment and implement the intervention allocation specified on the card. This procedure will result in the random allocation of 40 participants to 1 of 2 groups. All participants will receive standard medical management for PSD. Those assigned to the intervention group will additionally receive active taVNS, while participants in the control group will receive sham taVNS alongside standard care.
This study adopts a double-blind design: participants, all outcome assessors (including the neuro-otolaryngologist for FEES, ultrasonographer, and TMS operator), and statistical analysts remain blinded to group assignment. Therapists delivering taVNS or sham stimulation are the only staff aware of the allocation and are excluded from all outcome measurement and data analysis procedures.
Identical stimulators matching in appearance, weight, indicator lights, and sound prompts are used for both groups. Both the taVNS and sham taVNS groups receive real electrical stimulation with a fully unified set of parameters (waveform, frequency, adjustable intensity range, single-session duration, and weekly treatment frequency). The only difference between groups is the stimulation site: the taVNS group receives stimulation at the vagal-innervated concha region (Heart CO15 and Kidney CO10 acupoints), while the sham group receives stimulation at nonvagal scapha acupoints (Elbow SF3, Shoulder SF4-5), which lie outside the vagus nerve innervation zone. This design ensures that both groups experience identical cutaneous sensations, thereby maintaining effective blinding while avoiding vagal activation in the sham group. To mitigate unblinding risks stemming from inherent sensory differences between concha and scapha stimulation sites, targeted masking strategies are implemented. Stimulation intensity is adjusted per participant to achieve an equivalent mild tingling sensory experience at the respective auricular locations. All stimulation sessions are conducted in separate single-person treatment rooms, and participants cannot see electrode placement. Therapists follow standardized, neutral verbal guidance and avoid differential descriptions of stimulation sensations to prevent suggestive bias.
Blinding efficacy will be quantitatively assessed after the trial’s completion using the Bang Blinding Index (BBI), which is based on participants’ postintervention group guesses, as detailed in the Statistical Analysis section. Participants’ self-reported stimulation sensory experience will be collected for post hoc analysis to detect site-related sensory bias. Considering the anatomical differences between vagal and nonvagal auricular regions, between-group efficacy results will not be interpreted as purely vagus nerve–specific effects without confirmation of adequate blinding via the BBI.
Emergency unblinding is reserved exclusively for the independent safety officer when serious AEs occur that require targeted clinical intervention. All unblinding incidents, root causes, and timelines will be fully documented in the medical records and submitted to the institutional ethics committee in a timely manner.
The study design was adapted from the methodology used by Wang et al [
This study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Ethical approval for this study was obtained from the Research Ethics Committee of the Guangdong Second Hospital of Traditional Chinese Medicine on January 2, 2025 (Approval Number: Y202411-003-01). The trial was registered with the Chinese Clinical Trial Registry on January 21, 2025 (ChiCTR2500096311).
Written informed consent will be obtained from all participants prior to enrollment. Before recruitment, researchers will explain the study’s purpose, procedures, potential risks, and benefits to potential participants and their guardians. Participants will be informed that they may withdraw from the study at any time without affecting their medical care.
Data confidentiality will be maintained throughout the study. All participant-identifying information will be anonymized before analysis [
Any amendments to the study protocol will require unanimous agreement from the research team and will be formally documented by updating the clinical trial registry [
The Clinical Endpoints Committee consists of members of the Data Monitoring Committee and principal investigators who will review source data and medical events based on prespecified outcomes. The Steering Committee consists of the principal investigator, subinvestigators, rehabilitation department directors, and methodologists. The committee holds routine quarterly meetings to review recruitment progress, the incidence of adverse events, problems with protocol compliance, and any proposed protocol amendments. Any plans for trial adjustments must obtain unanimous written approval from all committee members before submission to the clinical trial registry and the ethics committee.
All enrolled participants will receive standard pharmacological treatment for stroke in accordance with the Chinese Stroke Prevention and Treatment Guidelines (2021 Edition) [
Patients will undergo daily sessions of physical and occupational therapy, each lasting 30 minutes.
The physical therapy protocol will comprise passive range-of-motion exercises, turning and repositioning training, muscle-strengthening activities, balance retraining, ambulation practice, and a range of low- to medium-frequency electrotherapies.
Occupational therapy will aim to enhance functional independence through activities of daily living training, joint mobility exercises, roller-based coordination activities, and ball-throwing tasks.
Behavioral swallowing therapy includes lip and tongue strength training, compensatory techniques for airway protection during swallowing, and cold thermal stimulation. Neuromuscular electrical stimulation is delivered via the VitalStim 590 swallowing therapy device (Enovis), targeting the suprahyoid and thyrohyoid muscles for 20 minutes per session, once daily.
All standard therapy components will be provided identically to all participants in both the taVNS and sham taVNS groups. The dose of each therapy component is standardized:
Pharmacological therapy was administered as per guidelines; dose and frequency were recorded for each participant.
Physical rehabilitation consisted of 30 minutes daily, 5 days a week.
Occupational therapy consisted of 30 minutes daily, 5 days a week.
Swallowing rehabilitation consisted of 20 minutes daily, 5 days a week.
Adherence to standard therapy will be recorded in daily therapy logs. Participants will be considered adherent if they complete at least 80% of scheduled therapy sessions. Therapy logs will be reviewed weekly by the study coordinator.
Patients assume a seated position. Before stimulation, the auricular sites and adjacent skin are disinfected with alcohol swabs. A Huatuo SDZ-IIB electronic stimulator (Suzhou Medical Appliance Factory Ltd), equipped with dedicated leads for channels A and B, is used to apply 2 pairs of auricular clips bilaterally to the cymba conchae and cavum conchae regions. Stimulation parameters are configured as follows: a dense-sparse wave mode (alternating between 4 Hz for 5 s and 20 Hz for 10 s), with an intensity ranging from 0.6 to 1.0 mA, adjusted in real-time according to patient tolerance. In the taVNS group, stimulation targets the Heart (CO15, located in the cavum conchae) and Kidney (CO10, situated in the cymba conchae) acupoints [
Annotated schematic of auricular anatomical regions. Solid black circles indicate active stimulation sites at the cymba conchae (CO10) and cavum conchae (CO15), where auricular vagal nerve branches are densely distributed. Solid red circles mark sham stimulation sites at elbow (SF3) and shoulder (SF4-5) points within the scapha, a vagal nerve–free zone to achieve sensory matching for the double-blind design. Standard auricular anatomical landmarks are labeled throughout the diagram.
Upon completion of the full intervention protocol, participants will receive a detailed report comparing their baseline clinical measures with posttreatment outcomes, accompanied by evidence-based recommendations aimed at reducing the risk of adverse clinical events.
The primary outcome will be assessed using the Rosenbek PAS [
Penetration is defined as the entry of liquid or food into the laryngeal vestibule, but not beyond the vocal folds. Aspiration, in contrast, refers to the passage of material below the vocal folds into the trachea and lungs. It is further classified as overt aspiration—accompanied by coughing or choking—or silent aspiration, which occurs in the absence of such protective reflexes.
The PAS classifies aspiration severity into 8 levels according to the depth of material invasion, its position relative to the vocal folds, and the patient’s ability to clear the airway. A score of 1 indicates that no material enters the airway, while a score of 8 represents material passing below the vocal folds with no effort to eject it [
Pharyngeal residue is defined as the incomplete clearance of both preswallow secretions and postswallow food remnants retained in the vallecula and pyriform sinuses [
MASA is a comprehensive tool widely used to assess swallowing function. It comprises multiple items evaluating key components of the swallowing process, such as mastication, swallowing coordination, and esophageal transit. Each item is scored based on standardized criteria, with a maximum total score of 100 points. The overall score is calculated as the sum of all individual items, where higher scores indicate swallowing function that is closer to normal [
A color Doppler ultrasound system (Wisonic Clover) with a 3 to 10 MHz curved array transducer will be used for hyoid movement assessment. The probe will be positioned sagittally along the midline below the mandible, covering the hyoid bone to visualize the tongue and hyoid dynamics during swallowing. Using the mandible as the coordinate origin, hyoid displacement will be quantified by measuring the coordinate difference between the resting position and the position at the peak of swallowing [
The identical probe will be positioned longitudinally along the midline, anterior to the larynx, with its superior aspect aligned over the hyoid bone and its inferior aspect covering the thyroid cartilage. Ultrasonic imaging will be performed during swallowing to quantify the extent of hyoid-thyroid approximation. An increase in the approximation distance reflects enhanced activation of the muscles involved in elevating the laryngeal complex [
A transcranial magnetic stimulator (M-100; Shenzhen Yingzhi Technology) equipped with a figure-of-eight coil (BY90A; Shenzhen Yingchi Technology) and an integrated MEP module was used for synchronous signal recording [
The TMS coil was positioned by the operator at a 45° angle relative to the cranial sagittal midline over the suprahyoid cortical hotspot. The left suprahyoid hotspot was localized 3.0±0.8 cm anterior and 4.1±0.9 cm lateral to the Cz point, while the right hotspot was identified 2.8±0.7 cm anterior and 4.0±0.7 cm lateral to the Cz point. Resting motor threshold (RMT) was determined through single-pulse stimulation. The stimulation intensity was then set to 120% of RMT, and multiple stimuli were delivered at randomized intervals. Five clearly reproducible MEP waveforms with the largest amplitudes were selected, and their latency and amplitude values were averaged for analysis.
MEP latency was defined as the time interval (in milliseconds) from cortical stimulation to the onset of the compound muscle action potential in the contralateral suprahyoid muscles.
MEP amplitude was defined as the peak-to-peak voltage (in millivolts), measured as the potential difference between the most negative and most positive peaks.
Reduced latency and increased amplitude are indicative of improved neural conduction velocity and enhanced cortical excitability. In this trial, TMS-MEP recordings were obtained bilaterally from the suprahyoid cortical areas to enable subgroup analyses and to examine the effects of taVNS on corticobulbar tract excitability.
The FOIS uses a 7-point scale that evaluates a patient’s functional oral intake by assessing their feeding methods and food consistency. Higher scores correspond to better oral intake ability [
All outcome assessments are carried out under uniform, standardized environmental and testing conditions to ensure measurement consistency. All trained assessors are fully blinded to group allocation and strictly independent of the therapists delivering taVNS or sham stimulation; no information about participant group assignment is shared between assessment and intervention staff.
FEES will be performed by a trained neuro-otolaryngologist who is blinded to group allocation. All FEES procedures will be video-recorded in their entirety.
The PAS and YPR-SRS will be scored independently by 2 trained assessors (both blinded to group allocation and to each other’s ratings) using the stored video recordings. Each assessor will score all recordings in a randomized order. If the 2 assessors’ scores disagree by more than 1 point on the PAS (or by >1 grade on the YPR-SRS), a third blinded assessor will review the recording and make the final decision. For disagreements of 1 point or less, the 2 assessors will discuss and reach a consensus.
Ultrasound assessments (hyoid bone displacement and hyoid-thyroid approximation) will be performed and measured by a trained ultrasonographer blinded to group allocation. TMS-MEP recordings will be performed and analyzed by a trained technician blinded to group allocation.
The primary time point for hypothesis testing is day 14 (immediately after the 2-week intervention period). The primary comparison is the difference in PAS scores between the taVNS and sham taVNS groups on day 14, adjusted for baseline PAS score.
Mechanistic outcomes (TMS-MEP parameters and hyoid movement measures) are considered exploratory. These outcomes will be analyzed descriptively and used to generate hypotheses for future research rather than to confirm mechanistic pathways.
In addition to the study intervention, patients will complete a series of assessments and data collection activities at specified time points: during enrollment (days −3 to −1), at allocation (days −1 to 0), and on days 14 and 44. The schedule for these procedures is detailed in
SPIRIT
| Study period | ||||
| Enrollment | Allocation | Postallocation | ||
| Time point (d) | –3 to –1 | –1 to 0 | 14 | 44 |
| Enrollment | ||||
| ✓ | ||||
| ✓ | ||||
| ✓ | ||||
| ✓ | ||||
| Interventions (the intervention will be delivered over a 14‑d period, with treatment administered on 10 d [5 d on, followed by 2 d off]) | ||||
| Assessments | ||||
| ✓ | ✓ | |||
| ✓ | ✓ | |||
| ✓ | ✓ | |||
| Suprahyoid muscle motor-evoked potentials (TMS-MEP | ✓ | ✓ | ||
| Adverse event records | ✓ | ✓ | ||
| FOIS | ✓ | ✓ | ✓ | |
| ECG | ✓ | ✓ | ||
aSPIRIT: Standard Protocol Items: Recommendations for Interventional Trials.
bThe intervention period will last 14 days, with treatment administered on 10 weekdays over 2 wk. Day 44 represents the 1-mo follow-up visit after completion of the 2-wk intervention.
ctaVNS: transcutaneous auricular vagus nerve stimulation.
dPAS: Penetration-Aspiration Scale.
eYPR-SRS: Yale Pharyngeal Residue Severity Rating Scale.
fMASA: Modified Mann Assessment of Swallowing Ability.
gTMS-MEP: transcranial magnetic stimulation motor-evoked potentials.
hFOIS: Functional Oral Intake Scale.
iECG: electrocardiogram.
Data will be recorded on standardized paper case report forms (CRFs) and transcribed into electronic databases by independent researchers blinded to group allocation. All participant identifiers will be anonymized prior to statistical analysis. Original CRFs will be archived securely in the hospital medical records department for 3 years after study completion, per institutional ethical requirements. Deidentified datasets can be shared with qualified researchers upon reasonable request to the corresponding author [
All statistical analyses will be conducted using SPSS (version 26.0; IBM Corporation) and R (version 4.2; R Foundation for Statistical Computing). Two-sided tests with α of .05 are adopted. All randomized participants will be analyzed following the intention-to-treat principle, and missing values will be reported for all variables. Multiple imputation with 20 datasets will be applied to missing outcome data, with complete-case analysis as a sensitivity check.
Continuous data will be summarized as mean (SD) for normally distributed variables or median (IQR) for skewed distributions, and categorical data will be presented as counts and percentages.
The primary end point, the PAS, is treated as continuous quantitative data rather than ordinal categorical data in this study. Although the PAS consists of discrete integer ratings, its ordered numeric scores represent gradual, incremental changes in swallowing penetration and aspiration severity, supporting the use of continuous linear modeling and a corresponding sample size calculation.
Linear mixed-effects models (LMMs) will be applied to all repeated quantitative outcomes, including PAS, the MASA, hyoid bone displacement, hyoid-thyroid approximation distance, TMS-MEP parameters, and the FOIS. Each LMM includes fixed effects of group allocation, assessment time point, group-by-time interaction, and a random intercept for each participant to account for within-subject correlation of repeated measurements. Baseline observations are incorporated as a single time point in the longitudinal model to adjust for interindividual baseline differences in swallowing function.
The repeatedly measured ordinal scale YPR-SRS will be analyzed using ordinal mixed-effects logistic regression, with fixed and random-effects structures identical to those of the LMMs. All mechanistic TMS-MEP indicators are defined as exploratory outcomes without multiplicity correction. Between-group comparisons for categorical safety data will use a chi-square test or Fisher exact test, as appropriate. Blinding efficacy will be quantified using the BBI [
Interim analyses will be performed at 2-month intervals, with preliminary results made available solely to the DMC and the principal investigator, who retains ultimate authority regarding trial continuation [
Patient safety will be monitored throughout the trial by an independent safety officer who has access to unblinded data [
AEs will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, graded from 1 (“mild”) to 5 (“death”). All AEs will be recorded in the CRFs, regardless of whether they are considered related to the intervention.
The relationship between any AE and the intervention will be assessed by the safety officer and principal investigator, categorized as: unrelated, unlikely, possibly, probably, or definitely related.
Vital signs (heart rate, blood pressure, and oxygen saturation) will be monitored before and after each stimulation session. Monthly meetings will be convened to review each participant’s clinical status and evaluate both treatment efficacy and safety.
The trial will be stopped if any of the following occur:
Any serious adverse event (SAE) assessed as possibly, probably, or definitely related to taVNS
Severe AEs (CTCAE grade ≥3) occurring in more than 20% of participants in either group
Two or more participants in either group experience a cardiac arrhythmia or significant bradycardia (heart rate <50 beats/min) during or immediately after stimulation
In the event of an SAE in which knowledge of the intervention is necessary for participant management, the independent safety officer will perform emergency unblinding. The reason for unblinding will be documented in the participant’s medical record and reported to the ethics committee.
All SAEs will be reported to the Research Ethics Committee of the Guangdong Second Hospital of Traditional Chinese Medicine within 24 hours of occurrence. A summary of all AEs (including type, grade, and relatedness) will be included in the annual progress report to the ethics committee.
An independent safety officer will monitor participant safety throughout the trial, with access to unblinded data if required for safety assessments. A DMC, comprising members of the Clinical Endpoints Committee and the principal investigator, will review source data and medical events based on prespecified outcomes at regular intervals. Data monitoring activities exclusively cover participant safety surveillance, AE review, interim data review, and early trial termination recommendations, and are entirely independent of routine data recording, CRF archiving, and deidentification procedures detailed in the Data Management subsection, which governs only static data storage rather than real-time safety oversight.
Monthly meetings will be convened to review each participant’s clinical status and evaluate both treatment efficacy and safety. The DMC will have access to interim analysis results, as described in the Interim Analyses subsection, and may recommend early trial termination if safety concerns arise.
The principal investigator will submit an annual progress report to the corresponding author and the Research Ethics Committee. The progress report will include the recruitment status, summary of AEs, and any protocol deviations. The Research Ethics Committee may conduct independent audits of trial conduct as deemed necessary [
Independent audits of trial source documents, medical records, and CRFs may be initiated by the institutional ethics committee at any time throughout the trial period. Upon receiving an audit notice, the principal investigator shall organize all trial-related documents (informed consent forms, therapy logs, AE records, and randomization envelopes) for on-site inspection. All identified protocol deviations will be documented with corrective action plans and tracked until full rectification, with audit summaries submitted to the ethics committee within 14 working days.
A quality control team, independent of the intervention and assessment teams, will conduct regular and ad hoc monitoring to verify data accuracy. Data collection will be supervised by an independent research assistant to ensure completeness and consistency.
Protocol deviations must be documented by researchers with a full description of the incident, its cause, corrective actions taken, and the signatures of responsible personnel. Noncompliance with the protocol that cannot be resolved may result in termination of the study.
During the statistical analysis phase, 2 independent research assistants will perform double data entry. They will conduct self-verification to identify any discrepancies in the entered data and promptly rectify any detected errors. These assistants will also be responsible for analyzing, evaluating, and reporting the potential impact of any protocol deviations on the final results and conclusions. All quality control and auditing records will be retained for inspection by the ethics committee or regulatory authorities.