Study design
This prospective, single-blind, randomized, controlled trial evaluated the therapeutic effectiveness and safety of KYXF in treating DAS. The patients will be recruited from the Rehabilitation Center of the First Affiliated Hospital of Henan University of Chinese Medicine. 60 patients who meet the inclusion and exclusion criteria will be randomly divided into 2 groups: the control group and the experimental group.
The control group will use routine speech training; the experimental group will use KYXF manipulation for 20 minutes based on the control group. Both groups will receive routine medical treatment, rehabilitation training, and speech training. All patients will be treated for 1 time/day, 5 days/week, and last for 8 weeks. Patients will be assessed at 5-time points: baseline (0 weeks), mid-treatment (4 weeks after treatment begins), end of treatment (8 weeks after treatment begins), and follow-up (12 weeks and 24 weeks after treatment finishes). The Frenchay score will be used to evaluate the efficacy of all patients[18]. The trial flow chart is shown in Fig. 1. The trial process chart is shown in Table 1.
Table 1
Timing of treatment assessments and data collection.
| | STUDY PERIOD |
| | Enrolment | Baseline | Treatment phase | Follow-up phase |
| TIMEPOINT | -1 Week | 0 Week | 4 Weeks | 8 Weeks | 12 weeks | 24 weeks |
| ENROLMENT | | | |
| Eligibility screen | x | | | | | |
| Informed consent | x | | | | | |
| Medical history | x | | | | | |
| Merger disease | x | | | | | |
| Randomization | | x | | | | |
| INTERVENTIONS | | | |
| Experimental-group | | x | x | x | | |
| Control group | | x | x | x | | |
| ASSESSMENTS | | | |
| Frenchay | | x | x | x | x | x |
| Adverse events | | x | | x | x | x |
| Safety evaluation | | x | | x | | |
Patients
Diagnostic basis
(1) The diagnostic criteria of stroke in Western medicine refer to the "Clinical diagnosis of patients with cerebrovascular disease"[19].
(2) The diagnostic criteria of stroke in TCM refer to "From clinical appearance to accurate management in acute ischemic stroke patients: With the guidance of innovative traditional Chinese medicine diagnosis"[20].
Inclusion criteria
(1) Patients aged ≥ 18 years and ≤ 70 years.
(2) Patients who meet the diagnostic criteria of stroke by computed tomography (CT) or magnetic resonance imaging (MRI), and their basic vital signs (temperature, pulse, respiration, blood pressure) are stable and can cooperate with treatment.
(3) Patients with a stroke course 2 weeks to 6 months,1 point ≤ National Institute of Health stroke scale (NIHSS) score ≤ 20 points and with mild or moderate dysarthria (14 ≤ Frenchay score ≤ 26)[21].
(4) Patients who agree to participate in this study and sign an informed consent form.
Exclusion criteria
(1) Patients who don’t meet the above inclusion criteria.
(2) Patients with severe heart, lung, liver, kidney disease, diabetes, osteoporosis, or severe bleeding tendency.
(3) Patients with systemic infection or severely unstable condition.
(4) Patients with aphasia, cognitive impairment, or severe dysphagia.
(5) Patients with severe dysarthria who cannot cooperate with treatment (Frenchay score ≤ 13)[21].
Suspension/Elimination/Shedding criteria
(1) Suspension criteria: Patients with severe adverse reactions; Due to problems in the study, patients’ efficacy cannot be judged.
(2) Elimination criteria: Patients who fail to cooperate with treatment as required; patients who don’t meet the inclusion criteria.
(3) Shedding criteria: Patients who drop out on their own.
Recruitment
This trial will recruit patients online and offline to help them better understand the research information. The hospital's official website and WeChat advertising are two types of online recruitment strategies. Posters, pictures, and videos are types of offline recruitment strategies. Recruitment information for these strategies will include the research's objective, methodologies, benefits and drawbacks. Each patient will undergo a preliminary assessment and screening by the researchers, strictly according to the abovementioned inclusion and exclusion criteria. Patients who meet the inclusion criteria will be asked to sign an informed consent form.
Randomization
We will adopt a completely random method. All patients will be randomly divided into two groups in a 1:1 ratio: Speech training plus KYXF group and speech training group. Randomization software will be commissioned to generate random number sequences by a professional statistician who is not involved in treatment and outcome assessment. Patients' information will be put into 60 numbered sealed and opaque envelopes, which could be opened after informed consent is obtained. Researchers must select patients according to the inclusion and exclusion criteria, then use random numbers to assign until the total number of patients (60).
Blinding
We cannot conduct a double-blind trial due to the nature of acupressure manipulation, and only the therapists are informed of the groupings and interventions of the study participants. One of the two efficient therapies will be given to patients randomly and they will not be informed of the other. To avoid communication between patients, they must be treated in a separate personal space and wear an eye patch. Furthermore, to prevent the influence of subjective factors on the therapists, we will select individuals with no conflicts of interest to participate in the trial. We will invite professional statisticians not involved in the research to assist with data management and statistical analysis.
Table 2
Treatment types and treatment time
| Type of rehabilitation | Method of treatment | Duration of treatment | Outcomes | Index |
| KYXF | PNF and acupressure | Once a day, 5 times a w, for 8 w | At baseline, 4 w, 8 w, 12 w, and 24 w after treatment | Frenchay |
| Speech training | Relaxation training, breathing training, vocal organ exercise training, articulatory training, rhythm training | Once a day, 5 times a w, for 8 w | At baseline, 4 w, 8 w, 12 w, and 24 w after treatment | Frenchay |
Interventions
The trial is divided into 2 groups: the experimental group (speech training plus KYXF) and the control group (speech training). At the same time, both groups of patients will receive conventional medical treatment and rehabilitation training 5 times a week for 8 weeks. Frenchay’s functional score will be assessed at baseline, mid-treatment, end of treatment, and follow-up. All physicians and therapists must have at least 3 years of clinical experience. The treatment types and treatment time are shown in Table 2, and the two groups of interventions are as follows:
Basic treatment
According to the condition of the two groups of patients, they will receive medical treatment, rehabilitation training, and routine speech training. Medical treatment mainly includes improving cerebral circulation, nourishing cerebral nerves, regulating blood pressure, blood sugar, blood lipids, etc. Rehabilitation training mainly includes exercise therapy, occupational therapy, physical therapy, and so on, helping patients enhance muscle strength, expand the joint range of motion, reduce muscle tone, and improve motor function. Routine speech training mainly includes:
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Relaxation training: Instruct the patient to take a deep breath and relax the muscles of all parts of the body, including the throat muscles, head, shoulders, neck, chest, abdomen, back, buttocks, legs, feet, etc.
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Breathing training: The patient takes a sitting position, inhales slowly through the nose, and then slowly exhales through the mouth. The therapist pays attention to the direction of movement of the diaphragm and ribs to improve respiratory control and lay the foundation for vocalization, pronunciation, and rhythm.
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Vocal organ exercise training: Including jaw training, lip training, tongue training, and soft palate training.
1) Jaw training: Instruct the patient to open and close the mouth as much as possible, repeat 5 times slowly, and then gradually increase the speed, but pay attention to keeping the range of motion between the upper and lower jaws as large as possible;
2) Lip training: Instruct the patient to move the upper and lower lips forward as far as possible, make a "u" sound, and then retract it as far back as possible, make an "i" sound, and repeat 5 times slowly. Then increase the frequency of alternating movements, trying to maintain a large range of motion of the lips;
3) Tongue training: Instruct the patient to extend the tongue as far as possible, retract it, and then roll it up, back, left, and right, repeating 5 times;
4) Soft palate training: Instruct the patient to sigh hard to promote the elevation of the soft palate or use cotton swabs to stimulate the soft palate directly. If the paralysis of the soft palate is mild, ice cubes can be used to stimulate the soft palate quickly for 1 to 3 s. This method can improve the muscle tension of the soft palate.
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Articulatory training: Instruct patients to keep their lips tightly closed, puff their cheeks as much as possible, continue to pronounce "ah", and try to pronounce vowels. Then the volume is controlled from small to large, then from large to small, and the volume is changed alternately.
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Rhythm training: Instruct the patient to read poetry, newspapers, or everyday conversations aloud as much as possible and pay attention to rhythm control, and the therapist helps the patient better control the rhythm by reminding the rhythm points.
Experimental group (speech training plus KYXF)
In addition to routine medical treatment, rehabilitation training, and speech training, patients in this group will receive KYXF for 20 minutes, 1 time/day, 5 days/week, and treatment for 8 weeks. KYXF will be divided into 5 operations:
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The operator places one hand thumb and index finger at the bilateral Fengchi (GB20) of the patient, the other hand on the patient's forehead, with both hands gently making the patient's head do a spiral diagonal movement (pendulum clock movement).
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The operator places one hand thumb and index finger at the bilateral Renying (ST9) of the patient, the other hand on the patient's posterior occipital, with both hands slightly against force, and ask the patient to try to lower the head, so that the mandible do a spiral diagonal movement.
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The operator places one hand thumb on the patient's Lianquan (CV23), the other hand thumb on the patient's Shuitu (ST10), two thumbs at the same time to do rotation kneading, and places one hand thumb and four fingers on the throat of the patient to do a rapid neck pendulum clock movement.
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The operator presses the bilateral Tiyan (In the posterior border of the mandible and lower border of the mastoid process) with both thumbs and presses the bilateral Tunyan (Between the hyoid and Adam’s apple, 0.5 cun lateral to the midline) with both forefingers, the patient is instructed to open the mouth with force and make sounds of ha, ga, ka to train the soft palate function.
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Strengthen respiratory function through resistance breathing training. The operator places one palm on the patient's lower abdomen and applies pressure, and the other places on the patient's back neck, both hands slightly resistant to force, and asks the patient to breathe through the abdomen. First resist inhaling, then resist exhaling, and quickly press the abdomen twice at the end of exhalation to increase abdominal pressure and empty residual gas as much as possible. During exhalation, the patient can cooperate with reading words or counting and ask to pronounce "ah" twice as loudly as possible when pressurizing at the end of exhalation. This method not only trains the respiratory function but also promotes soft palate lift and trains the ability to control speech volume. For the abovementioned five KYXF operations, each operation will be carried out independently and continuously 10 times, once all operations are completed, repeat the KYXF manipulation 1 time completely. The anatomical chart of acupoints is shown in Fig. 2. The locations are presented in Table 3.
Table 3
Location of acupoints for treating dysarthria after stroke
| Acupoints location |
| Fengchi (GB20) | In the posterior region of the neck, below the occipital bone, in the |
| | depression between the sternocleidomastoid and the upper end of |
| | the trapezius. |
| Renying (ST9) | In the neck, next to the laryngeal node, the leading edge of the |
| | sternocleidomastoid muscle, and the pulsation of the common |
| | carotid artery. |
| Lianquan (CV23) | In the neck, on the anterior midline, above the larynx, and in the |
| | depression of the upper edge of the hyoid bone. |
| Shuitu (ST10) | In the neck, the anterior edge of the sternocleidomastoid muscle, |
| | flat annular cartilage. |
| Tiyan (New point) | In the posterior border of the mandible and lower border of the |
| | mastoid process. |
| Tunyan (New point) | Between the hyoid and Adam’s apple, 0.5 cun lateral to the midline. |
Control group (Speech training)
Patients in this group will receive routine medical treatment, rehabilitation training, speech training, 1 time/day, 5 days/week, and therapy for 8 weeks.
Sample Size Estimation
The purpose of this clinical trial is to evaluate the safety and efficacy of KYXF in the treatment of DAS. Our early clinical study with a small sample (10 cases in each group) found that 2 weeks of the experimental group and the control group could improve scores on the Frenchay scale by 3.65 ± 1.38 and 2.44 ± 1.26 points, respectively. The significance test level is set to 0.05, and the test power is set to 0.9. The sample size is calculated as follows:
N = 2× [(Zα/2 +Zβ) × σ/δ]2 (1)
N is the sample size required for each group. When α is 0.05 and β is 0.1, the normal distribution quantile table shows the following:
$$\begin{array}{c}{Z}_{{\alpha }/2}=\text{1.96}\\ {Z}_{{\beta }}=\text{1.282}\end{array}$$
2
σ and δ represent the larger standard deviation and allowable error between the two groups, which are 1.38 and 1.21, respectively. The result is 27 by substituting these data into the formula, so the number of samples in each group is about 27. Therefore, there are 30 cases in the experimental group and 30 cases in the control group. (Including 10% shedding rate).
Quality Control
All researchers will be required to receive standard training before the study begins to guarantee the quality of this study. In addition, we will invite qualified clinical trial experts from the First Affiliated Hospital of Henan University of Chinese Medicine to monitor the data of this study and make detailed regulations on intervention, statistical analysis, and evaluation. If problems are discovered during the study, the trial plan can only be changed with the ethics committee's approval. A quality control team will regularly check whether the test procedures and data management meet the standards.
Outcome Assessments
Frenchay score is dysarthria's most widely used function assessment scale[8]. Originally, its contents include respiration, reflexes, palate, larynx, jaw, lips, tongue, and intelligibility, 8 major items, 29 minor items, each 29 minor items has 5 scoring criteria from “a” (normal) to “e” (severely abnormal)[18]. We adapted the FDA by replacing alphabetic coding with numeric scoring and rated 29 items on a 4-point scale. They are normal (4 points), mild abnormal (3 points), moderate abnormal (2 points), obvious abnormal (1 point), and severely abnormal (0 points)[21]. Evaluate the severity of dysarthria according to the proportion of normal items in the total items. In other words, the a-point items are totaled, and the rating score of the FDA ranges from 0 to 29 points. Grade: very severe:0–6/29; Severe:7–13/29; Moderate:14–17/29; Mild:18–26/29; Normal:27–29/29[21].
Safety Evaluation and Adverse Events
Blood routine, urine routine, pulse, electrocardiogram, and liver and kidney function will be measured before and after treatment to evaluate the safety of the study. During treatment, researchers will pay close attention to the patient's health. If someone has nausea, vomiting, and other adverse events, researchers will immediately deal with them and record them in detail on the Case Report Form (CRF). After treatment, researchers will analyze the incidence of adverse events, and patients involved in adverse events will be compensated.
Data Collection and Management
All patient information will be truthfully, completely, and accurately recorded in CRFs, including the treatment time, outcome assessment, adverse event, safety assessment, etc. The relevant data will be managed by data researchers, and the personal data of each patient will be kept strictly confidential. Without the written permission of the research group leader, data will not be shared with anyone other than data researchers. Researchers must submit the CRF on time at the end of this study, and the quality control team will evaluate its validity and completeness.
Statistical analysis
Statistical analysis will be performed using SPSS19.0 software for statistical analysis after all experimental data are verified correctly. The mean ± standard deviation (± S) will be used to indicate the centralized and discrete trends when the measurement data satisfies the normal distribution, paired T-test will be used for intra-group comparison and independent sample T-test will be used for inter-group comparison; If the normal distribution is not satisfied, the median and interquartile range (M, Q) will be used to represent the centralized and discrete trends, and the Wilcoxon rank-sum test will be used to analyze the difference; The count data will be analyzed by chi-square test; The test level will be set at 0.05, and P<0.05 is considered statistically significant.