Participants will be recruited and treated at the Community Health Service Center, Xindu Sub-district, Yancheng City (Jiangsu Province, China), the Community Health Service Center of Dongting Lake Street (Jiangsu Province, China). The measurement and follow-up of the trial will be performed in Jiangsu Vocational College of Medicine in Yancheng City, Jiangsu Province, China, which specializes in training medical staff for primary medical institutions.
Patients with chronic insomnia will be recruited from the primary healthcare centers where the general practitioners will perform the interventions. Individuals with co-morbidities will only be excluded if there is a life-threatening situation, or the use of study drugs is prohibited. Moreover, individuals who use psychotropic drugs (e.g., anti-anxiety drugs, antidepressants, benzodiazepines, or non-benzodiazepine sleep aids) will not be automatically excluded. Patients who have taken a stable dose of selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI) drugs (for at least 3 months), have at least partial relief of mood or anxiety disorders, and who meet the selection criteria will be included in the study. Patients who are taking monoamine oxidase inhibitors, tricyclic antidepressants, or atypical antidepressants will be excluded, even if they are in remission, due to the possibility that these drugs will confuse the interpretation of the study results .
The inclusion criteria are as follows: (1) patients who meet the diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)  and in the Criteria for Disease Diagnosis in TCM and TCM Therapeutic Efficacy ; (2) who are males or females > 18 years old; (3) who have difficulties in falling asleep or maintaining sleep for ≥ 1 month despite having enough opportunities to sleep, with an incubation period of sleep onset or the waking time after sleep onset exceeding 30 min (occurring at least 3 nights a week); (4) with > 10 insomnia severity index (ISI) total scores, indicating at least mild insomnia; and (5) who participate in this study voluntarily, can cooperate in completing various scale evaluations during the treatment period and in treatment, and provide informed consent.
The exclusion criteria are as follows: (1) patients with or suspected of having severe mental illness or suicidal tendencies; (2) with substance use disorders (including addition or abuse of substances such as alcohol, caffeine, sedative, and psychoactive drugs); (3) with history of epilepsy, mania, bipolar disorder, or parasomnia; (4) currently using drugs that may cause insomnia (e.g., steroids) and suspected of having severe sleep apnea (≥ 5 positive items in the snoring, tiredness, observed apnea, high blood pressure, body mass index, age, neck circumference, and male sex [STOP-Bang] questionnaire) , restless legs syndrome, circadian rhythm sleep disorders, personal or family (first degree relatives) parasomnia history; (5) who suffer from severe diseases, other exercise contraindications, or special conditions that are considered unsuitable for Wuqinxi qigong exercise; who are not suitable for sleep restriction and stimulation control therapy; or who have contraindications to trazodone and liver and kidney dysfunction; and (6) who have practiced Wuqinxi for a long time, have received or are receiving CBT-I treatment (including BT-I, online CBT-I, and self-help CBT-I) in other medical institutions.
Structured clinical interview
A structured clinical interview to screen potential participants has been developed by our group. The interview content is in accordance with the DSM-5  and the Duke structured interview for sleep disorder  and gives full consideration to the actual situation of primary medical institutions in the Chinese community. In the absence of a gold standard interview tool [40, 44], we have developed a questionnaire to obtain the history of sleep behavior and history of potential sleep disease of the candidates to allow physicians to rapidly diagnose insomnia and screen for other comorbid sleep disorders (i.e., sleep deprivation, lethargy, circadian rhythm sleep-wake disorder, severe sleep apnea, restless legs syndrome) to in primary medical institutions in China, and to facilitate the evaluation of eligibility for inclusion in this study.
The sleep diary based on the web-based follow-up system will be used to obtain subjective estimates of sleep and wake-up time of the participants daily. Each participant will be asked to cooperate with the follow-up staff to report the information about their sleep the night before, including bedtime, sleep onset latency, number and duration of nighttime awakenings, last awakening time, wake-up time, subjective evaluation of sleep quality, and use of sleep aid drugs. A 1-week sleep diary will be obtained in the first week after the study enrollment. During the telephone follow-up, the follow-up staff will give necessary guidance and supervision to ensure the patient’s adherence to behavioral therapy.
BBT-I adherence questionnaire
Good adherence to therapy is key to the curative effect of behavioral therapy . One of the main hypotheses of this study is that both the external TCM and trazodone can help patients to improve their therapeutic adherence. Unfortunately, there are currently few relevant studies and no gold standard for evaluating adherence with CBT-I or its brief model [22, 46, 47]. To evaluate the adherence of participants, our team devised the BBT-I adherence questionnaire based on the contents of sleep restriction and stimulus control, which focuses on the patient’s behavioral therapy adherence in the past week, including insistence on not going to bed at night without sleeping, getting up early in the morning, not going to bed during the day, not staying in bed at night after attempting to sleep for 30 min, and not doing anything unrelated to sleep or having sex (especially using cell phone and thinking). Each content will be scored from 0 to 3 as follows: score 0, difficult to accomplish; score 1, accomplish less than half the time; score 2, accomplish more than half the time; score 3, accomplish most of the time.
Main outcome indicator
The ISI will be used to evaluate the improvement of insomnia at the baseline level before the treatment, at the end of the 4-week treatment period, and 3 months after the end of treatment. A reduction in the ISI score of ≥ 8 points is considered effective, and an ISI score ≤ 8 is considered cured [48, 49]. The BBT-I adherence questionnaire will be used to evaluate the efficacy of TCMST or trazodone on the adherence of BBT-I.
Secondary outcome indicators
The secondary indicators of the disease evaluation will include the PSQI , Zung’s self-rating anxiety scale, Zung’s self-rating depression scale , patient’s sleep quality, mental state, and possible adverse reactions of the participants recorded during the follow-up.
Recruitment and consent
Through community clinics, Dr. Yongliang Zheng’s online workstation, the Good Doctor online app, promotion of community physical examinations, community health lectures, and other forms, patients with insomnia will be introduced and recruited to the clinical trial. General practitioners in primary healthcare centers use structured clinical interviews to identify potential participants meeting eligibility criteria. General practitioners then inform a monitoring group doctor to obtain informed consent from potential participants, and complete further screening assessments. The research group will obtain written informed consent from all participants during the enrollment, and the participants recruited on the online platform will be required to print and sign the electronic version of the informed consent form and send it back to the research group for archiving.
Eligible participants will be randomized into the experimental group or control group using a complete randomization scheme generated in advance. Specifically, the randomization scheme will be generated in the computer program Stata/SE15.1 by a member of the research staff (Liangliang Li) who is not involved in recruitment or intervention and is not the principal investigator. The assignment of participants will be hidden using sequentially numbered-sealed e-mails, which will only be opened by the researchers after the informed consent form is signed. The study grouping will be revealed at the same time to both the patient and researchers.
The standard treatment for insomnia will be BBT-I , including sleep restriction, stimulation control, and sleep hygiene education [9, 52–54]. The implementation of sleep restriction and stimulation control will be guided by trained community physicians in the outpatient clinics. The corresponding bedtime, wake-up time, and other related recommendations for behavioral treatment will be given to the participants according to their sleep conditions and will be adjusted during the follow-up based on the 1-week sleep diary. Sleep hygiene education will be conducted in the form of health lectures and online free consultations. Related video resources will also be distributed to allow participants to partake in further study to better understand their condition. Although complete CBT-I may be the best treatment option, BBT-I is a standard treatment that can be conducted in primary medical institutions in the Chinese community because of its simple and easy implementation.
Considering the various non-adherence issues that occur in the implementation of BBT-I, we will schedule TCMST in BBT-I to improve patient’s behavioral adherence in the experimental group. TCMST include Wuqinxi qigong exercise, Chinese medicine massage, and herbal foot bath. (1) Wuqinxi qigong will be exercised when participants who fail to fall asleep half an hour after going to bed, and cannot fall asleep again half an hour after waking up early. Wuqinxi consists of five parts: Tiger Exercise, Ape Exercise, Bear Exercise, Crane Exercise, and Deer Exercise. Exercise recommendation is based on the five elements theory of traditional Chinese medicine. According to the five elements theory, Tiger Exercise corresponds to anger, so practicing Tiger Exercise can ease the anger mood. Similarly, Ape Exercise corresponds to joy, Bear Exercise corresponds to thinking, Crane Exercise corresponds to sadness, and Deer Exercise corresponds to panic. Therefore, for participants who are unable to fall asleep due to irritability or anger, he or she will be suggested to get out of bed to practice Tiger Exercise. For participants who are unable to fall asleep due to joy, he or she will be suggested to get out of bed to practice Ape Exercise. For participants who are unable to fall asleep due to worries, they will be recommended to get up to practice Bear Exercise. For participants who are unable to fall asleep due to sadness, he or she will be required to get out of bed to practice Crane Exercise. For participants who are unable to fall asleep due to panic, he or she will be required to get out of bed to practice Deer Exercise . (2) Participants who have difficulty cooperating with sleep restriction at night (postponing bedtime) will be prescribed Chinese medicine foot bath by an attending physician dialectically based on the TCM theory, with no uniform limitations. The time of the Chinese medicine foot bath will be half an hour before bedtime at night as recommended by the physicians. (3) Participants who feel tired during the day and have difficulty cooperating with the implementation of daytime sleep restriction will be given Chinese massage, with no specific restrictions on the duration, acupoints, and techniques of the massage. The therapist will implement the Chinese massage according to the specific conditions of the participants.
Participants in the control group will be given standard treatment based on BBT-I combined with oral trazodone medication (25–150 mg trazodone as an adjuvant therapy, 30 min before going to bed). Trazodone is selected because it is one of the most common drug prescriptions for insomnia in clinical practice [56–59]. If the patient refuses to take trazodone, we will provide BBT-I only and record it.
Once the research candidates have completed several written screening measures, those who meet the inclusion criteria will be screened and evaluated, with the results used as the baseline assessment data. The candidates will be randomly treated in the experimental (i.e., BBT-I combined with TCMST) and control (i.e., BBT-I combined with oral trazodone medication) groups, all of whom must complete the 4 weeks of corresponding treatments. In the first week, the follow-up staff will assist the patient to complete a 1-week sleep diary by telephone, during which, the follow-up staff will provide the necessary guidance and supervision to ensure the participants’ behavioral therapy adherence. After the first week, the participants will be instructed to adjust the behavioral treatment plan. In the second and third weeks, the participants’ behavioral therapy adherence will be followed up with the BBT-I adherence questionnaire, and guidance to ensure behavioral therapy adherence will be given during the follow-up. At the end of the fourth week, sleep and mood-related scales will be evaluated, and the BBI-I adherence questionnaire will be performed again. Participants who demonstrate an improvement will continue maintenance therapy, and participants with no improvement over the 4-week study period will have their treatment plan adjusted or will be recommended to be referred to a higher-level hospital. During the treatment period, the treatment will be discontinued in participants who cannot cooperate with the treatment due to disease or other reasons.
Three months after the end of the 4-week treatment, a telephone follow-up will be performed to evaluate the therapeutic efficacy. All follow-up tasks above will be conducted through the network chronic disease follow-up platform (NCDFP) developed by Jiangsu Vocational College of Medicine (Jiangsu Province, China), and will be completed by trained students through the telephone interview. Table 1 shows the participant timeline, and Fig. 1 provides an overview of the study.
Participants who have been taking hypnotic drugs or antidepressants before enrollment will be permitted to continue taking them; however, the addition of hypnotic drugs or treatment other than the given interventions during trial will be prohibited if the participants did not take them before enrollment.
Data processing and analysis
The baseline demographics of the research subjects will be collected by the attending physician through paper-and-pen records at the time of recruitment and will be entered into the database. The data during the treatment and follow-up period will be collected by follow-up staff using the NCDFP, an online telephone survey, which will allow participants to perform this at their convenience. All participants will be reminded throughout the study to fill out the questionnaires during study visits. The follow-up process will be recorded in real time to verify the accuracy of the data. The project manager will be responsible for double checking and exporting the original data from the follow-up system to the required format for data analysis. After the study is completed, the pattern of missing data will be investigated to determine whether the data are completely missing at random or missing non-randomly . Our preliminary analysis will use a robust statistical model, and a sensitivity analysis of nonrandom missing data will be performed if necessary .
Analysis of the validity and reliability of the BBT-I adherence questionnaire: the adherence reliability of the behavioral therapy will evaluate the internal consistency of the behavioral therapy adherence through the standard Cronbach’s α coefficient and the total correlation coefficient of the item. Convergence validity analysis will be based on the participants’ 1-week daily sleep diary, which will be compared with the consistency of the questions answered in the BBT-I adherence questionnaire to observe whether the questionnaire truly reflects the accuracy of the patient’s adherence with various behavioral treatments. For example, for the question “Can you get up on time in the morning in the last week?” if the patient’s answer is “accomplish less than half the time” then the patient should have gotten up on time 1–3 days during the last week; if the patient’s answer is “accomplish more than half the time,” the sleep dairy of this patient should indicate that he or she has gotten up on time for 4–6 days in the last week; if the patient’s answer is “not able to accomplish,” the sleep dairy of this patient should indicate that he or she had 0 days getting up on time in the last week; if the patient’s answer is “accomplish most of the time,” the sleep diary of this patient should indicate that he or she has gotten up on time for all 7 days in the last week. Waking up on time is defined as getting up no more than 15 min before or after the agreed time to get up. Failure to meet the above criteria will be considered inconsistency between questionnaire’s answer and the sleep diary. Lastly, the consistency ratio will be determined, and the correlation coefficient will be calculated.
Analysis of therapeutic efficacy within and between groups, and adherence analysis between the groups: the measurement data will be presented as the mean ± standard deviation, and the statistical inference will be performed using the t-test and rank-sum test. The count data will be presented as frequency (composition ratio), and chi-square analysis or nonparametric analysis will be performed for exact probability or statistical inference, respectively. Subgroup analysis will be used to analyze the main outcome and adherence according to the sex and education level of the research subjects. SPSS 21.0 software (IBM, Armonk, NY) will be used for statistical analysis, which will adopt two-sided tests. P ≤ 0.05 will be considered to indicate statistically significant differences in the test.
Sample size calculation
The main observation index of this study is the ISI, and the sample size is calculated based on the two independent sample t-test. The sample size adjustment is based on the pool variance . According to our previous reports [25, 49], the mean effect size of the control group is 8.4. A mean effect size difference (δ) of an increase in 2.5 for the experimental group relative to the control group will be considered effective. The overall sample standard deviation of ISI in the previous study was 4.1 . Assuming that the variances of the two groups are similar, in a two-sided test with α at 0.05, sample size ratio of the two groups at 1:1, the test power (1-β) at 80%, the sample size is calculated to be 88. We anticipate 10% loss to follow-up or drop-off rate. Thus, t total sample size is calculated as 96.8, which is approximately 98 people, including 49 people in each of the two groups.
Composition And Responsibilities Of The Coordinating Center
This study is a multicenter study that will be designed, performed, and coordinated in Jiangsu Vocational College of Medicine, Community Health Service Center of Dongting Lake Street and the Community Health Service Center of Xindu Street. The study team will meet weekly. The trial is supported by:
(1) Monitoring group: supervises the trial, audits data, takes medical responsibility for the participants, provides BBT-I, and trains the follow-up group.
(2) Physician group: identifies potential recruits, acquires informed consent, provides medical treatment according to the study protocol.
(3) Follow-up group: conducts follow-up by telephone and records data in the NCDFP, feeds back questions to the Physician group, and safeguards data.
(4) Supportive group: performs trial registration, safety reports, and coordinates with each team.