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Clinical Study Protocol

J Acupunct Meridian Stud 2024; 17(3): 100-109

Published online June 30, 2024 https://doi.org/10.51507/j.jams.2024.17.3.100

Copyright © Medical Association of Pharmacopuncture Institute.

Intraoral Acupuncture for Sialorrhea in Stroke Patients: a Study Protocol for a Randomized Controlled Trial

Jin-Jin Wang1,2,* , Meng-Meng Shao2 , Xue-Zhen Zhou2 , Zu-Chen Lin2 , Hai-Yan Li2 , Zheng-Zhong Yuan3 , Qin-Qin Ma2 , Fang Li2 , Wen-Bin Fu1,4*

1The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China
2Department of Rehabilitation Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
3Department of TCM, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
4Department of Acupuncture and Moxibustion, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China

Correspondence to:Jin-Jin Wang
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China, Department of Rehabilitation Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
E-mail wangjinjin@wmu.edu.cn

Wen-Bin Fu
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China, Department of Acupuncture and Moxibustion, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China
E-mail fuwenbin@139.com

Received: January 9, 2024; Revised: February 27, 2024; Accepted: May 22, 2024

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients.
Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients.
Design: Clinical study protocol, SPIRIT compliant.
Setting: Prospective, single-center, randomized, and sham-controlled trial.
Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients.
Exposures: Intraoral or sham acupuncture.
Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the “Drooling Severity and Frequency Scale” and “Functional Oral Intake Scale.”
Results: The results from this study will be published in peer-reviewed journals.
Conclusion: Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.

Keywords: Sialorrhea, Patients with stroke, Intraoral acupuncture, Study protocol

Trial registration: Chinese Clinical Trial Registry: ChiCTR2200058191.

INTRODUCTION

Sialorrhea—or excessive drooling or hypersalivation—occurs when saliva extends beyond the lip border. This phenomenon, considered normal in infants, typically ceases by the age of 15-18 months. However, sialorrhea persisting beyond the age of 4 years is regarded as a pathological condition [1-5]. Post-stroke sialorrhea (PSS) is characterized by excessive saliva accumulation, unintentional leakage from the lip margin, and frequent swallowing or spitting, in individuals who experienced a stroke. Currently, PSS has no universally agreed definition.

Sialorrhea can have distressing consequences, including the potential for damaging books and computers, soiling clothes, halitosis, and unpleasant odors from clothes, leading to social rejection by friends and caregivers [5,6]. Moreover, it can negatively impact a patient’s self-image, social communication, and mental health. From a psychological standpoint, excessive sialorrhea can reduce self-esteem and cause social isolation [5,7,8].

Current interventions for sialorrhea primarily involve using anticholinergic drugs, salivary gland-targeted radiotherapy, botulinum toxin injections, and surgical interventions [8-14]. However, these drugs have side effects [5,15-19], including xerostomia, urinary retention, and blurred vision, which have limited tolerability by patients, particularly older ones with multiple concurrent chronic illnesses. Additionally, xerostomia and dysphagia, the two most frequent treatment-related side effects, can hinder swallowing function recovery in stroke patients [20].

Surgical interventions for managing sialorrhea involve procedures performed on the salivary glands and ducts, such as submandibular duct relocation, submandibular gland excision, parotid duct relocation, and parotid duct ligation. These surgical approaches may have potential complications, such as external scarring, ranulas (mucous cysts), and sialoceles (salivary gland cysts) [5,8,10-13].

Salivary gland-targeted radiation therapy may be a viable option for older patients who are ineligible for surgery and intolerant to medication-based treatments [21]. Nonetheless, radiation therapy carries the potential risk of inducing malignancies and halitosis [22,23].

As mentioned above, medications, surgery, and radiation therapy can primarily improve sialorrhea symptoms by reducing salivary secretion. However, they are not viable options for PSS management, as little evidence supports the hypothesis that excessive salivary production is the root cause of PSS. Furthermore, medications, surgery, and radiotherapy have various adverse effects and are not entirely appropriate for stroke patients. Moreover, these methods are expensive and difficult to perform and are not suitable for promotion in community hospitals or clinics.

Acupuncture—a form of complementary therapy rooted in traditional Chinese medicine (TCM)—has been employed in China for treating stroke since ancient times; it involves simple operation, has low costs and is easy to promote. Intraoral acupuncture is a common acupuncture method in TCM and has demonstrated effectiveness in treating dysphagia and sialorrhea in children with cerebral palsy [24] and post-stroke dysphagia [25,26]. A small-scale prospective study [27] demonstrated the positive effect of tongue acupuncture in reducing sialorrhea in children. Additionally, acupuncture therapies targeting Jinjin (EX-HN-12), Yuye (EX-HN-13), and the posterior pharyngeal wall have been recommended for treating pseudobulbar paralysis after stroke [28]. However, no large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients.

Therefore, we aim to address this gap using this prospective, randomized controlled trial. This study aims to compare 1) the effects of intraoral acupuncture with those of sham acupuncture in PSS patients and 2) changes in salivary volume and swallowing function before and after treatment to investigate whether the underlying cause of PSS is primarily excessive salivary secretion or dysphagia.

MATERIALS AND METHODS

1. Study design

We designed a prospective, single-center, randomized, and sham-controlled trial that follows the guidelines outlined by the Consolidated Standards of Reporting Trials [29] and adheres to the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture [30] and the Standard Protocol Items: Recommendations for Intervention Trials (SPIRIT) guidelines [31]. Additional File 1 contains the SPIRIT checklist.

To compare the effects of intraoral acupuncture with those of sham acupuncture in patients diagnosed with PSS, we will recruit 106 stroke patients with PSS, randomly assigned to receive intraoral or sham acupuncture for 4 weeks. We will use a sham device, a blunt needle (the tip will be cut off), for sham acupuncture in the control group. This study will investigate whether intraoral acupuncture could improve sialorrhea symptoms in stroke patients by comparing changes in salivary secretion and sialorrhea severity before and after treatment in the two patient groups.

To clarify whether PSS is caused by excessive salivary secretion or swallowing difficulties, we plan to compare changes in salivary secretion and swallowing function before and after treatment between the two patient groups. Additionally, 53 stroke patients without PSS will undergo a routine treatment program for 4 weeks to compare salivation between PSS and non-PSS patients. Finally, we will perform a correlation analysis between drooling severity and salivary secretion and between drooling severity and swallowing function to identify correlations between drooling and changes in salivary secretion and swallowing function.

The trial will span 9 weeks, including 1 week of screening (weeks 0-1), 4 weeks of intervention (weeks 0-4), and 4 weeks of follow-up (weeks 5-8). Baseline, week 4, and week 8 evaluations are planned to document treatment progression. The research design and schedule are depicted in Fig. 1 and Table 1, respectively.

MMSE = Mini-Mental State Examination; 3MSW = 3-min saliva weight; DSFS = Drooling Severity and Frequency Scale; Drooling Score = Drooling Severity + Drooling Frequency; FOIS = Functional Oral Intake Scale..

&md=tbl&idx=1' data-target="#file-modal"">Table 1

Study schedule of enrollment, intervention, and assessments.

Study period
TimepointEnrollment AllocationTreatment phaseFollow-up phase
Week -1Week 0Week 2Week 4Week 6Week 8
Enrolment
Eligibility screen
Informed consent
Demographics
Stroke type
History of stroke
History of disease
MMSE
Allocation
Interventions
Intraoral acupuncture group‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒►
Control group‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒►
Conventional treatment group‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒►
Assessments
3MSW
DSFS
Drooling severity
Drooling frequency
Drooling score
FOIS
Safety
Adverse events

MMSE = Mini-Mental State Examination; 3MSW = 3-min saliva weight; DSFS = Drooling Severity and Frequency Scale; Drooling Score = Drooling Severity + Drooling Frequency; FOIS = Functional Oral Intake Scale..


Figure 1. Flow diagram illustrating the allocation of participants to different study conditions. The flow diagram was prepared per the Consolidated Standards of Reporting Trials guidelines. MMSE = Mini-Mental State Examination; 3MSW = 3-min saliva weight; DSFS = Drooling Severity and Frequency Scale; FOIS = Functional Oral Intake Scale.

2. Participants

We will recruit 106 stroke patients with PSS and 53 stroke patients without PSS from the inpatient and out­patient departments of the rehabilitation facilities at the First Affiliated Hospital of Wenzhou Medical University. Recruitment will be performed through hospital posters, WeChat (a popular social application in China), and online advertisements. Participants will be allocated into three groups: conventional treatment (53 stroke patients without PSS), intraoral acupuncture (53 PSS patients), and control groups (53 PSS patients).

1) Inclusion criteria

Participant inclusion criteria include: 1) stroke patients aged 35-75 years; 2) confirmed diagnosis of ischemic stroke or cerebral hemorrhage based on brain computed tomography or magnetic resonance imaging, with a stable medical condition and clear awareness; 3) stroke occurrence within the past 6 months; 4) sialorrhea symptoms in the intraoral acupuncture and control groups and no sialorrhea symptoms in the conventional treatment group; 5) sufficient cognitive ability to comprehend and follow instructions and a Mini-Mental State Examination score of ≥ 24; 6) treatments for sialorrhea are not being undertaken and are not planned (including drugs that reduce saliva secretion, surgery, and botox injections); and 7) willingness to participate voluntarily in the research and provide signed informed consent.

2) Exclusion criteria

Participants with any of the following criteria will be excluded: 1) history of sialorrhea; 2) dysphagia caused by other diseases, including, Parkinson’s disease, malignant throat disease, head and neck radiotherapy history, and tracheotomy; 3) presence of a concurrent chronic disorder, such as severe motor neuron disease, cardiac blood supply system disease, or cancer; 4) bleeding tendencies that may pose risks during acupuncture procedures; 5) known oversensitivity or allergy to acupuncture that may lead to adverse events (AEs); 6) developmental malformations, including incomplete lip closure and tracheal malformations, which may lead to sialorrhea; and 7) temporomandibular joint disorder and other reasons that may cause difficulty in opening the mouth.

3) Dropout criteria

The intervention will be terminated if 1) participants experience serious AEs during treatment, such as continuous bleeding, severe vomiting, and syncope; 2) during the trial, participants require other treatments that affect salivary secretion or swallowing function owing to changes in the illness; 3) participants voluntarily request to discontinue participation in the trial or withdraw their informed consent; 4) changes in the participants’ condition that require stopping trial or their transfer to other departments, and 5) salivary secretion affected by oral ulcers or other oral diseases during treatment.

3. Randomization and blinding

The central randomization system provided by the Wenzhou Medical University will be used for randomization. Eligible participants (with PSS) will be randomly and evenly allocated to the control or oral acupuncture groups. Additionally, the same number of stroke patients without PSS will be recruited into the conventional treatment group. The grouping order will be generated using a computer. IBM SPSS Statistics for Windows, version 26 (IBM Corp., Armonk, NY, USA) will be employed for generating random numbers.

To ensure allocation concealment, an independent resear­cher will perform randomization. Once the profile of each eligible participant is entered into the randomization system, random numbers and group assignments will be promptly emailed to the independent evaluator. This procedure will ensure that randomization is adequately concealed, free from the influences of the acupuncturists and participants.

To maintain blinding, patients, evaluators, and statistical analysts will not be aware of the treatment allocation throughout the study. However, because of the interventions’ nature, acupuncturists will not be blinded to the treatment allocation. Nevertheless, they will be instructed not to discuss treatment procedures or responses with the participants or outcome assessors. Blinding will only be disclosed in cases of serious AEs, when determining appropriate treatment methods is necessary.

4. Interventions

Differently sized Jiachen sterile needles (Wujiang Jiachen Acupuncture Devices Co. Ltd., Wujiang City, Jiangsu Province 215212, China) and KWD-808I electroacupuncture apparatus (Changzhou Wujin Great Wall Medical Instruments Co. Ltd., Wujin City, Jiangsu Province 213161, China) will be used to treat limb dysfunction (if necessary). The interventions in the three groups will be conducted by three acupuncturists who hold a master’s degree, are registered practitioners of TCM, and have at least 5 years of clinical experience in acupuncture practice. Before study initiation, the acupuncturists will be instructed on the research scheme and standard acupuncture methods.

1) Permitted and prohibited concomitant treatments

During the entire 4-week intervention period, the rehabili­tation treatment will be administered to all patients in the three groups five times a week. The rehabilitation programme will follow the Chinese Stroke Rehabilitation Treatment Guidelines and include activities such as swallowing function training, physical therapy, and occupational therapy, which will be conducted for 5 days each week [32].

Additionally, conventional symptomatic treatment will be allowed, following the Chinese guidelines for diagnosing and treating cerebral infarction and hemorrhage [33,34]. These may include administering antihypertensive drugs, blood sugar regulation medications, lipid-lowering drugs, and platelet aggregation inhibitors. However, medications that specifically affect salivary secretion will not be added unless necessary because of the participant’s condition.

Moreover, based on the procedures outlined in the book “Acupuncturology [28]”, all patients will receive acupuncture treatment on their head, limbs, and face five times a week to improve dysfunction. Acupuncture will not be performed at the Dicang (ST 4), Chengjiang (CV 24), Xiaguan (ST 7), or acupoints in the neck to avoid affecting salivary secretion. The acupuncturists will adjust the therapeutic points on the head and limbs according to each patient’s condition.

2) Conventional treatment group

Fifty-three stroke patients without PSS will be recruited, receive the above conventional treatment, and complete target monitoring at the appropriate time points.

3) Intraoral acupuncture group

Fifty-three PSS patients will be randomly assigned to the intraoral acupuncture group. Besides the conventional treatment, these patients will receive intraoral acupuncture five times a week for 4 weeks.

(1) Acupuncture sites for the intraoral acupuncture group

The following acupuncture sites will be used: 1) Jinjin (EX-HN-12), located within the mouth, specifically on the vein on the left side of the frenulum of the tongue (Fig. 2) [28], and 2) Yuye (EX-HN-13), located within the mouth, specifically on the vein on the right side of the frenulum of the tongue (Fig. 2) and on the posterior pharyngeal wall on both sides of the uvula (Fig. 3) [28].

Figure 2. Illustration of the targeted acupuncture sites. Jin-Jin (EX-HN-12) location: on the vein on the left side of the frenulum of the tongue. Yu-Ye (EX-HN-13) location: on the vein on the right side of the frenulum of the tongue.
Figure 3. Illustration of the targeted acupuncture sites. Posterior pharyngeal wall on both sides of the uvula.

During the operation, the patient will remain in a supine position. The mandible will be slightly lifted, and the patient will be instructed to open their mouth and make an “ah” sound. Next, the tongue body will be gently pressed with a spatula, and the posterior pharyngeal wall will be exposed. Thereafter, a 0.25 × 75 mm needle with a tube will be placed on the acupuncture site; the acupuncturist will quickly flick the body end of the needle with their right middle finger and quickly withdraw the needle after its tip has punctured the mucous membrane at a 2-3 mm depth (Fig. 3). The patient will be instructed to press their tongue against their upper jaw to expose veins on both sides of the lingual frenulum. Subsequently, the Jinjin and Yuye acupoints will be similarly pricked once (Fig. 2). Each site will be needled once in each treatment session. Intraoral acupuncture will not leave needles, and manual manipulation will not be performed. Needling is effective if the patient experiences mild pain at the treatment site and evasive head action. Severe pain, massive bleeding, tears, and vomiting will be avoided as far as possible.

4) Control group

Fifty-three PSS patients will be randomly assigned to the control group and will receive sham acupuncture five times a week for 4 weeks and undergo designated assessments at specified time points.

(1) Sham acupuncture

To ensure implementation of the blinding method and to avoid patients’ perception of differences between intraoral acupuncture and the control groups, we will use a Takakura sham device [35], a skin-touch placebo needle (the tip will be cut off) of 0.25 mm diameter to depress the skin 2 mm from the surface, for sham acupuncture to cause a pricking sensation that mimics real acupuncture without actually puncturing the oral mucosa. According to the results of Takakura et al. [35], to achieve a 2-mm stimulation depth, the length of the blunt needle will be measured when its tip is cut off to ensure that it exceeds the tube length by 2 mm.

After the patient’s acupuncture site is exposed, the blunt needle with a tube will be placed on the puncture point. The acupuncturist will use their right middle finger to quickly flick the tail of the needle body; the blunt needle will compress the mucous membrane, causing it to sink by 2 mm. The patient will feel the stimulation, and the needle will be quickly withdrawn. The sham acupuncture will not leave needles, and manual manipulation will not be performed.

Except for differences in the needles used, the acupuncture operation method and acupuncture site selection in the control group are the same as those in the intraoral acupunc­ture group. Because the needle tip will be removed, although the patient will feel the touch of the needle, there will be no bleeding or puncture of the oral mucosa at the acupuncture site.

There are two reasons for choosing a blunt needle with a tube as a sham device for the sham-acupuncture control. First, using this device, patients can be effectively blinded to the treatment method as they cannot distinguish between treatment methods owing to needles, operation methods, or their perception. Second, although the blunt needle will compress the oral mucosa to produce stimulation, it will not puncture the mucosa or cause pain or bleeding, and its stimulation is far less than that of conventional acupuncture; thus, it will be an effective control.

5) Follow-up

Following the completion of the intervention phase, all participants will enter a 4-week follow-up period. Given the slow recovery of limb dysfunction following stroke, patients in all three groups may require ongoing rehabilitation and acupuncture treatment. However, during this time, none of the stroke patients in the three groups will receive intraoral acupuncture treatment. All patients from the three groups will undergo reassessment using the 3-min saliva weight (3MSW), Functional Oral Intake Scale (FOIS), and Drooling Severity and Frequency Scale (DSFS) at week 8. Upon com­pletion of the experiment, the researchers will collect all the evaluation scales and forms for further analysis and review.

5. Outcome measures


1) Primary outcome measurement

This study primarily aims to assess the variation in the 3MSW from the initial measurement to weeks 4 and 8. This will serve as the primary outcome for evaluating the intervention’s effectiveness. The differences in the 3MSW between the groups will be assessed. To more clearly reflect the difference in the salivary secretion amount among different participants, the change in the 3MSW, rather than the salivary flow rate, will be directly compared.

Saliva will be obtained following the procedure outlined by Rotteveel et al. [36]. Additional File 2 details the method for measuring the salivary secretion amount.

2) Secondary outcome measurements
(1) “Drooling Severity and Frequency Scale (DSFS)”

The average differences in DSFS scores between baseline and week 4 and between baseline and week 8 will be compared among the three groups. A validated scale will be used to assess drooling severity and frequency based on a questionnaire provided to the primary caregiver at baseline, week 4, and week 8.

DSFS includes two subscales: the severity scale of DSFS (DSFS-S) and the frequency scale of DSFS (DSFS-F) (Table 2). DSFS-S is scored using a 5-point Likert scale, with 1 being normal and 5 being extremely severe sialorrhea, while DSFS-F is scored using a 4-point Likert scale, with 1 being no sialorrhea and 4 being continuous sialorrhea.

Table 2

Drooling Severity and Frequency Scale (DSFS) [5].

DroolingPoints
Severity
Dry (never drools)1
Mild (wet lips only)2
Moderate (wet lips and chin)3
Severe (clothing becomes damp)4
Profuse (clothing, hands, tray, andobjects become wet)5
Frequency
Never drools1
Occasionally drools2
Frequently drools3
Constantly drools4


Finally, the drooling severity and frequency scores will be summed to obtain a combined drooling score ranging from 2 to 9. Higher scores will indicate more severe sialorrhea symptoms.

(2) “Functional Oral Intake Scale (FOIS)”

Comparative analysis among the three groups will involve assessing the mean difference in FOIS scores from baseline to weeks 4 and 8. FOIS comprises seven levels, each representing a distinct level of oral feeding ability and non-oral feeding requirements (Table 3). Lower scores on the scale indicate more pronounced dysphagia symptoms in stroke patients. To ensure accuracy and consistency, we will employ the validated Chinese version of FOIS [37].

Table 3

Functional Oral Intake Scale (FOIS) [38].

Fois items
Level 1:Nothing by mouth.
Level 2:Tube-dependent with minimal attempts of food or liquid.
Level 3:Tube-dependent with consistent oral intake of foodor liquid.
Level 4:Total oral diet with a single consistency.
Level 5:Total oral diet with multiple consistencies but requiring special preparation or compensations.
Level 6:Total oral diet with multiple consistencies without special preparation but with specific food limitations.
Level 7:Total oral diet with no restrictions.


6. Adverse events

The acupuncturists will examine and document any AEs that participants might experience. These include the emergence or worsening of unfavorable signs, symptoms, or diseases, such as sweating, pallor, dizziness, fainting, local hematoma, bleeding, intense tingling or numbness, local allergic reactions, acupuncture retention after treatment, and local infections. Additional File 3 presents additional AEs and summarizes compensation details.

In the event of an severe AE, the researcher is responsible for promptly reporting and submitting the severe AE report to our hospital’s Clinical Research Ethics Committee for review within 24 h.

7. Statistical considerations


1) Sample size

Given that limited literature exists on this topic, we conducted a preliminary experiment involving five partici­pants in the control and intraoral acupuncture groups. The change in salivary volume before and after treatment was 0.169 ± 0.447 g/3 min in the control group and –0.031 ± 0.061 g/3 min in the intraoral acupuncture group. To determine the sample size required for the main study, we considered a two-sided significance level of 5% and a power of 80%. The data (0.169, –0.031, 0.447, 0.061, α = 0.05, 1 – β = 0.8) were entered into NCS-PASSV15. Based on the related calculations, each group would require approximately 42 participants to achieve an adequate sample size, accounting for an estimated 20% dropout rate; therefore, each group must include 53 participants. To determine whether PSS patients have a greater salivary volume than those with stroke without sialorrhea symptoms, we will enroll 53 stroke patients without PSS in the conventional treatment group.

2) Statistical analysis

IBM SPSS Statistics for Windows, version 26 (IBM Corp., Armonk, NY, USA) will be employed for statistical analyses. If participants withdraw from the trial, intention-to-treat (ITT) analyses will be conducted, using baseline observations carried forward to impute the missing values. Continuous data will be presented as means and standard deviations or medians and quartile ranges, while categorical data will be presented as frequencies and percentages. Paired t-tests or non-parametric tests will be used to compare continuous data with baseline values, and nonparametric tests will be used for ranked data. Independent t tests or nonparametric tests will be used for between-group comparisons of continuous data, and nonparametric tests will be used for ranked data. Finally, a two-tailed test with a significance level of 5% will be applied.

8. Data management and quality control

We have extensively consulted with experts in acupuncture, rehabilitation medicine, and neurology to refine the research program. Before initiating the study, all personnel will undergo thorough training to ensure a comprehensive under­standing of the research protocol. This training will equip them with the necessary knowledge and understanding to execute the research program effectively.

The study will be conducted at the First Affiliated Hospital of Wenzhou Medical University. The institutional ethics com­mittee will be responsible for the safety and quality control of this study. Two independent researchers will collect and carefully verify all the data in the medical records and case report forms. Additionally, the Data Monitoring Committee of the First Affiliated Hospital of Wenzhou Medical University, a third party independent of researchers and sponsors, will monitor the data quality and review the data every 6 months. To ensure high quality, the research team will conduct regular online meetings to discuss any issues encountered during the study and devise appropriate solutions.

All the data will be stored in the Department of Rehabili­tation Medicine of our hospital. The data generated in this trial will be made available upon reasonable request to the corresponding author via email. Finally, the evaluation data and biological samples obtained in this study will not be used for other purposes.

9. Ethics and dissemination

This study will be conducted following the principles of the Declaration of Helsinki. The study was approved by the Ethics Committee of Clinical Research of the Wenzhou University (approval number: KY2022-015). Any modification to the experimental design will first be approved by the ethics committee. Before enrollment in the trial, the participants will need to sign informed consent to confirm their agreement to participate. Moreover, informed consent will be obtained by two designated staff members in a dedicated clinic room within the hospital. Participants or their legal guardians will receive detailed information regarding the trial, including its objectives, interventions, potential benefits, risks, and other relevant aspects. Participants will have the right to withdraw from the study at any time, and if they choose to do so, their data, that is related to the study, may still be included in the final analysis. The participants’ personal information will be kept confidential.

Regardless of whether the trial results are favorable or unfavorable, they will be published in peer-reviewed journals. The selection of authors for the article will be based on their contributions to the study.

DISCUSSION

To the best of our knowledge, no large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients. Additionally, limited evidence supports the link between excessive salivation and PSS. Therefore, we aimed to address this gap in this prospective, randomized controlled trial.

In this trial, we hypothesize that intraoral acupuncture can effectively alleviate increased salivation in stroke patients, and we aim to compare its effects with those of sham acupuncture in individuals diagnosed with PSS to test this hypothesis.

Although the current primary approach for treating PSS focuses on reducing salivary secretion, there is limited evidence establishing a causal relationship between hypersalivation and PSS. In contrast, Proulx et al. reported that patients with Parkinson’s disease secrete less saliva than healthy individuals [39]. A previous study that examined drooling in patients with Parkinson’s disease suggested that drooling is more attributable to impaired swallowing than excessive salivary production [40]. Additionally, in clinical practice, dysphagia is observed in 8.1-80% of stroke patients [41]. However, the role of dysphagia in PSS remains unclear, and we hypothesize that salivation in stroke patients may not be primarily driven by increased saliva secretion. As a secondary objective, we will investigate the relationships among salivary secretion, severity and frequency of drooling, and swallowing function in stroke patients under rigorous quality control measures.

By comparing the effects of intraoral and sham acupuncture in PSS patients, this research may improve future PSS treatments. Moreover, the findings herein may provide valuable insights into whether the sialorrhea observed in stroke patients can be attributed to heightened salivary secretion or dysphagia. Additionally, this study will offer evidence for re-evaluating current treatments (such as anticholinergic drugs, salivary gland-targeted radiotherapy, botulinum toxin injections, and surgery) for managing sialorrhea symptoms by reducing salivary secretion from different perspectives. However, it should be noted that the complexity of intraoral acupuncture may lead to the inability to use placebo acupuncture in this study, presenting a significant limitation. Furthermore, due to the nature of the intervention, it is not possible to blind the acupuncturist to treatment allocation, which could introduce bias.

CONCLUSIONS

By comparing the effects of intraoral and sham acupuncture in PSS patients, this research may contribute important evidence for future PSS treatment. The findings of this trial may provide valuable insights into whether the salivation issues observed in stroke patients can be attributed to heightened salivary secretion or dysphagia.

TRIAL STATUS

Participant recruitment is scheduled for between March 1, 2022 and July 31, 2024 and is currently underway.

FUNDING

This work was supported by the scientific research fund of the First Affiliated Hospital of Wenzhou Medical University and the Construction Project of “Ren Ye Famous Traditional Chinese Medicine Expert Inheritance Studio” (grant number GZS2021030). The funding sources had no involvement in the study design and will be not involved in the execution, data analysis, interpretation, manuscript writing, or decision to submit the results.

AUTHORS’ CONTRIBUTIONS

Jin-Jin Wang: Conceptualization, Methodology, Software, Writing – original draft; Meng-Meng Shao: Visualization, Conceptualization, Methodology; Xue-Zhen Zhou: Resources; Zu-Chen Lin: Resources; Qin-Qin Ma: Investigation; Fang Li: Investigation; Hai-Yan Li: Formal analysis, Methodology, Data curation; Zheng-Zhong Yuan: Methodology, Funding acquisition; Wen-Bin Fu: Supervision, Methodology, Data curation, Writing – review & editing.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Fig 1.

Figure 1.Flow diagram illustrating the allocation of participants to different study conditions. The flow diagram was prepared per the Consolidated Standards of Reporting Trials guidelines. MMSE = Mini-Mental State Examination; 3MSW = 3-min saliva weight; DSFS = Drooling Severity and Frequency Scale; FOIS = Functional Oral Intake Scale.
Journal of Acupuncture and Meridian Studies 2024; 17: 100-109https://doi.org/10.51507/j.jams.2024.17.3.100

Fig 2.

Figure 2.Illustration of the targeted acupuncture sites. Jin-Jin (EX-HN-12) location: on the vein on the left side of the frenulum of the tongue. Yu-Ye (EX-HN-13) location: on the vein on the right side of the frenulum of the tongue.
Journal of Acupuncture and Meridian Studies 2024; 17: 100-109https://doi.org/10.51507/j.jams.2024.17.3.100

Fig 3.

Figure 3.Illustration of the targeted acupuncture sites. Posterior pharyngeal wall on both sides of the uvula.
Journal of Acupuncture and Meridian Studies 2024; 17: 100-109https://doi.org/10.51507/j.jams.2024.17.3.100

Table 1 . Study schedule of enrollment, intervention, and assessments.

Study period
TimepointEnrollment AllocationTreatment phaseFollow-up phase
Week -1Week 0Week 2Week 4Week 6Week 8
Enrolment
Eligibility screen
Informed consent
Demographics
Stroke type
History of stroke
History of disease
MMSE
Allocation
Interventions
Intraoral acupuncture group‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒►
Control group‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒►
Conventional treatment group‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒‒►
Assessments
3MSW
DSFS
Drooling severity
Drooling frequency
Drooling score
FOIS
Safety
Adverse events

MMSE = Mini-Mental State Examination; 3MSW = 3-min saliva weight; DSFS = Drooling Severity and Frequency Scale; Drooling Score = Drooling Severity + Drooling Frequency; FOIS = Functional Oral Intake Scale..


Table 2 . Drooling Severity and Frequency Scale (DSFS) [5].

DroolingPoints
Severity
Dry (never drools)1
Mild (wet lips only)2
Moderate (wet lips and chin)3
Severe (clothing becomes damp)4
Profuse (clothing, hands, tray, andobjects become wet)5
Frequency
Never drools1
Occasionally drools2
Frequently drools3
Constantly drools4

Table 3 . Functional Oral Intake Scale (FOIS) [38].

Fois items
Level 1:Nothing by mouth.
Level 2:Tube-dependent with minimal attempts of food or liquid.
Level 3:Tube-dependent with consistent oral intake of foodor liquid.
Level 4:Total oral diet with a single consistency.
Level 5:Total oral diet with multiple consistencies but requiring special preparation or compensations.
Level 6:Total oral diet with multiple consistencies without special preparation but with specific food limitations.
Level 7:Total oral diet with no restrictions.

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