Clinical efficacy of meridian differentiation acupuncture in the treatment of intractable insomnia based on objective data: a protocol for a multicentre, single-blind, randomised controlled trial

Abstract

Introduction

Insomnia, a prevalent sleep disorder, significantly impacts individuals' physical and mental well-being. Despite conventional treatments, some patients experience persistent insomnia. Acupuncture, a safe complementary therapy, has been demonstrated to be effective in treating insomnia. Meridian differentiation can enhance acupuncture efficacy by enabling individualised diagnosis. Previous clinical research has indicated that meridian differentiation acupuncture (MA), based on objective data, can notably enhance sleep quality in patients with intractable insomnia. However, small sample sizes and a lack of objective measures necessitate further investigation. Therefore, we plan to conduct a large-scale, multicentre clinical trial to validate its efficacy.

Methods

We propose a multicentre, single-blind, randomised, sham acupuncture (SA)-controlled trial involving 489 participants with intractable insomnia. Patients will be randomly assigned to three groups at a 1:1:1 ratio: the MA group, the conventional acupuncture group and the SA group. We will assess Pittsburgh Sleep Quality Index scores, actigraphy, sleep diary, Insomnia Traditional Chinese Medicine Symptom Scale scores, Hamilton Rating Scale for Anxiety scores and meridian imbalance values at baseline, after 2 weeks and 4 weeks of treatment, and at two follow-up periods (8 weeks and 12 weeks postbaseline). The intention-to-treat principle will be applied to analyse the data, observe differences between meridian differentiation acupuncture, CA and SA in improving outcomes related to intractable insomnia.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee of the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine (2024HL-002) and the ethics committees of other participating institutions. Each participant must provide their written informed consent form before enrolling in this study, and consent can be withdrawn at any stage. On completion of the study, the results will be published in a journal or made available by contacting the corresponding author via email.

Trial registration number

This study protocol was registered in the Chinese Clinical Trial Registry on 22 April 2024 (ChiCTR2400083323).

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The selection of acupuncture points for this study took a semistandardised form, containing the ‘Tiaowei Jiannao’ acupoint group and the dorsal Back-shu points of the imbalance meridian.

• The study used a sham acupuncture control to blind the patients.

• The study only involved adults.

• The three centres of the study are all in the same region.

Introduction

Insomnia is a common sleep disorder. Epidemiological data suggest that approximately 25% of adults experience dissatisfaction with their sleep, and approximately 6%–10% meet the criteria for insomnia disorder.¹ Cognitive behavioural therapy (CBT) is the first-line treatment for insomnia,² yet its effectiveness hinges on patient compliance.³ While hypnotic drugs have significant short-term effects, their long-term use is discouraged due to the risks of abuse and dependence.⁴,⁶ Intractable insomnia, also termed refractory insomnia or treatment-resistant insomnia, is a type of insomnia that is resistant to conventional treatment and is characterised by a prolonged course and difficulty in resolution.⁷ The pathogenesis of intractable insomnia remains unclear; some studies suggest that N-methyl-D-aspartic acid (NMDA) receptor deficiency in the lateral preoptic area of the hypothalamus plays a crucial role in the high degree of sleep–wake fragmentation observed in intractable insomnia.⁸ Chronic sleep deprivation increases the risk of various diseases, such as cardiovascular and metabolic diseases, and cancer.⁹,¹² Additionally, it serves as a predisposing factor for numerous psychiatric disorders,¹³ including schizophrenia,^{14 15} depression¹⁶ and an increased likelihood of suicidal ideation.¹⁷ Consequently, there is a necessity to explore complementary and alternative therapies for intractable insomnia, diverging from CBT and beyond pharmacologic mechanisms, to enhance patients' sleep quality and mitigate potential risks.

Acupuncture emerges as a promising treatment for intractable insomnia. First, a number of systematic reviews have confirmed its efficacy, demonstrating significant improvements in sleep duration and quality among patients with primary insomnia, especially compared with sham acupuncture (SA) and hypnotic drugs.¹⁸,²⁰ Acupuncture achieves these effects by regulating various physiological pathways, including inhibiting the overactive hypothalamic–pituitary–adrenal axis^{21 22}; modulating inflammatory cytokines such as Interleukin 1, Interleukin 6 and Tumor Necrosis Factor-α (TNF-α)^{23 24}; and influencing neurotransmitters such as Gama-aminobutyric acid (GABA), 5-Hydroxytryptamine (5-HT) and norepinephrine.^{25 26} Second, given the chronic nature of intractable insomnia and its propensity to precipitate emotional disturbances,²⁷ acupuncture emerges as a multifaceted intervention capable of addressing both sleep disturbances and associated psychological symptoms, such as anxiety and depression.²⁸,³⁰ In contrast to the potential adverse effects associated with hypnotic medication, including dependence, withdrawal, cognitive impairment and falls/fractures,⁶ acupuncture emerges as a safer alternative.³¹

The strength of traditional Chinese medicine lies in ‘giving treatment on the basis of syndrome differentiation’, focusing on individualised diagnosis and treatment tailored to each patient’s condition. Meridian identification plays a crucial role in diagnosis and treatment, which traditionally relies on the combination of the four diagnostic methods to pinpoint diseased meridians and provide targeted therapy. However, this approach’s subjectivity hinders its applicability in clinical trials. Jing-Well points, which reflect both meridians and Zang-Fu organs’ function, offer potential for objective assessment. Several studies have investigated the biological and physical properties of Jing-Well points, such as point resistance, heat sensation and temperature. These studies generally reveal two key characteristics: balanced data on Jing-Well points in a healthy state and imbalanced data on Jing-Well points in a pathological state, particularly in meridians closely linked to disease development.³²,³⁶ This phenomenon provides an opportunity for objective meridian identification. Our preliminary research involved testing the heat pain sensation of Jing-Well points in patients with intractable insomnia. The results indicated concentrated imbalances in the Pericardium Meridian, Heart Meridian and Kidney Meridian, consistent with traditional Chinese medicine principles. A subsequent clinical trial demonstrated the effectiveness of meridian identification acupuncture in treating intractable insomnia.³⁷ However, due to the small sample size and lack of objective indicators, we plan to conduct a large-scale, multicentre clinical trial with additional SA controls and objective measures to enhance the credibility and quality of the results.

Trial objectives

The main objective of this trial is to evaluate the effectiveness of meridian differentiation acupuncture (MA) in enhancing sleep quality among patients with intractable insomnia. This assessment encompasses enhancements in Pittsburgh Sleep Quality Index (PSQI) scores, actigraphy, sleep diary and Insomnia Traditional Chinese Medicine Symptom Scale (I-TCMS) score. The secondary objective is to examine the alleviation of patients' anxiety symptoms, along with changes in the meridian imbalance values (MIVs). Additionally, the correlation between the MIVs and objective sleep data will be investigated.

Method/design

Trial design

The study protocol used a multicentre, single-blind, randomised, SA-controlled method. Patients with intractable insomnia were randomly allocated into three groups at a 1:1:1 ratio: the MA group, the conventional acupuncture (CA) group and the SA group. The primary objective was to investigate the efficacy and safety of MA for the treatment of intractable insomnia based on objective data. This study protocol adheres to the Standard Protocol Items: Recommendations for Interventional Trials guidelines³⁸ and was registered in the Chinese Clinical Trial Registry on 22 April 2024 (ChiCTR2400083323). The findings will be reported following Consolidated Standards of Reporting Trials guidelines. ³⁹The study started in May 2024 and is planned to end in December 2027.

Setting

The trial will be conducted at the Third Affiliated Hospital of Henan University of Chinese Medicine, Henan Provincial Chest Hospital and the Fifth Affiliated Hospital of Zhengzhou University in Zhengzhou City, Henan Province, China.

Participants

Patients who met the diagnostic criteria for intractable insomnia will be included in the study. At the time of diagnosis of chronic insomnia, according to the International Classification of Sleep Disorders, Third Edition,⁴⁰ the duration of the disease is more than 6 months, and there is no significant improvement in symptoms after conventional treatment (treatment lasts for more than 1 week), a diagnosis of intractable insomnia can be made. Conventional treatment includes CBT and pharmacotherapy (including benzodiazepines, non-benzodiazepines, melatonin receptor agonists, antidepressants with sedative effects, orexin receptor antagonists, traditional Chinese medicines and proprietary Chinese medicines). For the purposes of this trial, we require patients to have tried both CBT and one or more pharmacotherapies.

Eligibility criteria

Inclusion criteria

Participants eligible for inclusion in this study must meet the following seven criteria: (1) meeting the diagnostic criteria for intractable insomnia; (2) aged between 18 and 65 years old (inclusive 18 and 65 years old); (3) having a total PSQI score of >7; (4) capable of independently completing various rating scales; (5) having intact limbs, with no scarring or ulceration of the skin at the Jing-Well points; (6) voluntarily participating in the trial, with the patient signing an informed consent form and (7) strictly complying with the trial specifications and completing the researchers' treatment programme.

Exclusion criteria

Participants meeting any of the following criteria will be excluded: (1) women who are breastfeeding or pregnant; (2) patients who cannot tolerate needle stimulation, are prone to needle fainting or have needle allergies; (3) left-handed individuals and (4) insomnia arising from other sleep disorders or secondary to other diseases.

Elimination and dropout criteria and processing measures

Elimination and dropout criteria

Participants meeting any of the following conditions will be excluded or considered dropout cases: (1) experiencing serious adverse reactions caused by the trial; (2) unable to adhere to treatment or cooperate in completing it; (3) developing other illnesses that render them unfit to continue participating in the study and (4) voluntarily withdrawing from the study or missing scheduled visits for any reason, failing to complete the prescribed course of treatment and observation cycle outlined in the protocol.

Processing measures

For all participants who are eliminated or dropout, the cause and time should be documented, and the necessary assessment items should be completed. Those who dropout due to adverse reactions should be promptly addressed, and an adverse event record form should be completed. Data on all eliminated and dropout participants are kept on file and analysed according to the intent-to-treat principle at the end of the trial.

Interventions

Basic measures

All three groups of patients were educated on sleep hygiene and meridian testing by a specialist physician. They were allowed to continue taking their medication regularly under the supervision of the specialist if necessary, but had to keep a detailed daily record of their medication type and dosage, especially noting any reduction in dosage. No patient would be allowed to increase their medication dosage unless it was deemed necessary after assessment by a specialist. The MIV was measured using a specific sensory meridian tester (TST200, Henan Zhiling Medical Equipment Co, China), with the detection probe temperature set at 45°C (±0.5°C). The 12 meridian Jing-Well points on both sides were tested sequentially when the probe reached the set temperature, and the time for the skin at each Jing-Well point to transition from warmth to pain was recorded in milliseconds. When the MIV was ≥1, the meridian was considered to be imbalanced. The location and order of the measurement points are illustrated in figure 1.

Figure 1. 12 Jing-Well points positioning and testing sequence. Red numbers, the order in which Jing-Well points are detected. BL, Bladder Meridian; GB, Gallbladder Meridian; HT, Heart Meridian; KI, Kidney Meridian; LI, Large Intestine Meridian; LR, Liver Meridian; LU, Lung Meridian; PC, Pericardium Meridian; SI, Small Intestine Meridian; SP, Spleen Meridian; ST, Stomach Meridian; TE, Triple Energiser Meridian.

MA group

The acupoints of the MA group were selected as Baihui (Governor vessel (GV 20)) point, Si Shencong (Extra point in common use-Head and neck (EX-HN 1)) point, bilateral Shenmai (Bladder Meridian (BL 62)) point, bilateral Zhaohai (Kidney Meridian (KI 6)) point and the Back-shu points of the imbalance meridian. The locations of the points are shown in figure 2, and the affiliation between the meridians and the Back-shu points is shown in table 1. All acupoints were treated with real acupuncture. The patient was placed in a prone position, and the acupoints were routinely disinfected. The patient was placed in a prone position with routine disinfection of acupoints. Needles at BL 62, KI 6 and the Back-shu points of the imbalance meridian were fixed using the Park sham device (PSD).⁴¹ The PSD was adhered to the skin surface over each acupoint, and needles were inserted through its plastic tube to a depth of 12 mm. Due to the physiological constraints of the head, needles at GV 20 and EX-HN 1 were secured with the hair-mounted hook-and-loop fastener instead of the PSD, inserted flatly to 12 mm depth. The structure of the PSD is illustrated in figure 3.

Figure 2. Location of acupuncture points. a,b,c,d: EX-HN 1. GV 20 and EX-HN 1 are fixed points. The Back-shu points are chosen according to the meridian imbalance. EX-HN, Extra point in common use-Head and neck; GV, Governor vessel; BL, Bladder Meridian; KI, Kidney Meridian; B-cun, Body cun.

Table 1. Back-shu points corresponding to the 12 meridians.

Meridians	Back-shu points	Location
Lung Meridian (LU)	Feishu (BL 13)	In the upper back region, at the same level as the inferior border of the spinous process of the third thoracic vertebra (T3), 1.5 B-cun lateral to the posterior median line
Large Intestine Meridian (LI)	Dachangshu (BL 25)	In the lumbar region, at the same level as the inferior border of the spinous process of the fourth lumbar vertebra (L4), 1.5 B-cun lateral to the posterior median line
Pericardium Meridian (PC)	Jeuyinshu (BL 14)	In the upper back region, at the same level as the inferior border of the spinous process of the fourth thoracic vertebra (T4), 1.5 B-cun lateral to the posterior median line
Triple Energiser Meridian (TE)	Sanjiaoshu (BL 22)	In the lumbar region, at the same level as the inferior border of the spinous process of the first lumbar vertebra (L1), 1.5 B-cun lateral to the posterior median line
Heart Meridian (HT)	Xinshu (BL 15)	In the upper back region, at the same level as the inferior border of the spinous process of the fifth thoracic vertebra (T5), 1.5 B-cun lateral to the posterior median line
Small Intestine Meridian (SI)	Xiaochangshu (BL 27)	In the sacral region, at the same level as the first posterior sacral foramen, and 1.5 B-cun lateral to the median sacral crest
Spleen Meridian (SP)	Pishu (BL 20)	In the upper back region, at the same level as the inferior border of the spinous process of the 11th thoracic vertebra (T11), 1.5 B-cun lateral to the posterior median line
Liver Meridian (LR)	Ganshu (BL 18)	In the upper back region, at the same level as the inferior border of the spinous process of the ninth thoracic vertebra (T9), 1.5 B-cun lateral to the posterior median line
Stomach Meridian (ST)	Weishu (BL 21)	In the upper back region, at the same level as the inferior border of the spinous process of the 12th thoracic vertebra (T12), 1.5 B-cun lateral to the posterior median line
Gallbladder Meridian (GB)	Danshu (BL 19)	In the upper back region, at the same level as the inferior border of the spinous process of the 10th thoracic vertebra (T10), 1.5 B-cun lateral to the posterior median line
Kidney Meridian (KI)	Shenshu (BL 23)	In the lumbar region, at the same level as the inferior border of the spinous process of the second lumbar vertebra (L2), 1.5 B-cun lateral to the posterior median line
Bladder Meridian (BL)	Pangguangshu (BL 28)	In the sacral region, at the same level as the second posterior sacral foramen, and 1.5 B-cun lateral to the median sacral crest

Figure 3. Illustration of Park Sham Device. The blunt tip of sham acupuncture does not stick into the skin.

CA group

The following acupoints were selected for the CA group: Baihui (GV 20) point, Si Shencong (EX-HN 1) point, bilateral Shenmai (BL 62) point and bilateral Zhaohai (KI 6) point. The acupoints were treated with real acupuncture. The patient was placed in the prone position after routine disinfection. Needles at bilateral Shenmai (BL 62) point and bilateral Zhaohai (KI 6) point were fixed using the PSD. The PSD was adhered to the skin surface over each acupoint, and needles were inserted through its plastic tube to a depth of 12 mm. Needles at Baihui (GV 20) point and Si Shencong (EX-HN 1) point were secured with the hair-mounted hook-and-loop fastener, inserted flatly to 12 mm depth. To minimise patient bias, SA was administered at the Back-shu points of the imbalanced meridian in the CA group.

SA group

The acupoints of the SA group were selected as Baihui (GV 20) point, Si Shencong (EX-HN 1) point, bilateral Shenmai (BL 62) point, bilateral Zhaohai (KI 6) point and the Back-shu points of the imbalance meridian. All points were operated on by SA. The patients were positioned prone, following routine skin disinfection. A sticky adhesive pad and a plastic catheter base were affixed to the skin surface. The blunt needle at all points was fixed using the PSD or the hair-mounted hook-and-loop fastener and does not pierce the skin, but when it comes into contact with the skin, it causes a relatively mild stinging sensation, which is used to blind the patient. The patients in the SA group underwent 20 free compensation treatments at the end of the final visit point according to their wishes.

Each group received treatment once per day for 30 min, 5 days a week, with 2 days of rest, over a 4-week period. All procedures were conducted by physicians with more than 1 year of medical practice experience and who standardised training in operating procedures before the trial commenced.

Outcomes

Primary outcome

Pittsburgh Sleep Quality Index

The PSQI comprises seven factors: sleep quality, sleep latency, total sleep time, sleep efficiency, sleep disturbances, use of sleep medications and daytime dysfunction. Each factor is scored from 0 to 3 based on the severity of the disorder. The total PSQI score ranges from 0 to 21, with higher scores indicating poorer sleep quality.

Secondary outcomes

Actigraphy

The actigraph (wGT3X-BT, LLC, USA) is a wrist-worn device that records objective sleep data and analyses it using ActiLife6 software (V.6.13.5, ActiGraph, LLC). These data include sleep latency, total sleep time, sleep efficiency, wake after sleep onset, number of awakenings and other relevant parameters.

Sleep diary

The sleep diary⁴² was used to document patients' subjective sleep status. Patients were instructed to record their daily sleep patterns from enrolment until the conclusion of the intervention. At baseline and during two follow-up periods, sleep was documented over three consecutive days in conjunction with actigraph. The sleep diary comprised two sections: the presleep record and the postwake record. The presleep records included information on daytime rest status, alcohol and caffeine consumption, and medication use. The postwake records documented the time of going to bed, time of falling asleep, sleep latency, total sleep time, number and duration of night-time awakenings, sleep quality and morning energy levels.

I-TCMS score

The I-TCMS consists of eight common clinical symptoms associated with insomnia, covering both sleep-related symptoms and comorbid conditions. Each item is scored from 0 to 3 based on its severity, with a total score ranging from 0 to 24. Higher scores reflect more severe sleep disturbances.

Hamilton Rating Scale for Anxiety (HAM-A)

The HAM-A was used to evaluate the mental status of the patients. This scale categorises anxiety symptoms into somatic and psychiatric domains, comprising a total of 14 scoring items. Each item is rated on a scale of 0–4 based on its severity, resulting in a total score ranging from 0 to 56. Higher scores indicate more pronounced anxiety symptoms.

Meridian imbalance values

The MIV is employed to evaluate the degree of left–right balance of the 12 meridians. Before and after the treatment, the duration for the skin of the Jing-Well points on both sides of the meridians to transition from warmth to pain was measured in milliseconds (ms). The MIV is calculated as the absolute difference between the left and right Jing-Well point values (ms), divided by the minimum value of both sides (ms). The MIV ≥1 indicates a state of meridian imbalance, with a higher value signifying a greater degree of imbalance.

Others

Blinding assessment

The blinding assessment will be conducted with the patient at the conclusion of the treatment, and the patient will be asked to respond to the following question: ‘do you believe you received acupuncture treatment?’ with the options ‘yes’, ‘no’ or ‘not sure’.

Treatment compliance

The anticipated and realised number of treatments for each patient will be computed to evaluate treatment adherence.

Procedure and participant timeline

Enrolment eligibility will be assessed based on the inclusion/exclusion criteria at the initial patient visit. Following this, the informed consent form will be explained, and signatures will be obtained from eligible subjects. Subsequently, the patients will be randomised and assigned to groups by clinicians at each centre through a centralised randomisation system. Both randomisation grouping and needling will be performed by the same individual. The outcomes will be tested and recorded at each visit by a physician unaware of the grouping. Finally, the data will be analysed and compiled by a third party who will not be involved in the trial. The trial flow and schedule are depicted in figure 4 and table 2.

Figure 4. Participant recruitment and study flow diagram. CA, conventional acupuncture; HAM-A, Hamilton Rating Scale for Anxiety; I-TCMS, Insomnia Traditional Chinese Medicine Symptom Scale; MIV, meridian imbalance values; MA, meridian differentiation acupuncture; PQSI, Pittsburgh Sleep Quality Index; SA, sham acupuncture;

Table 2. Time schedule of enrolment, interventions and assessments.

Timepoint	Baseline	Treatment period		Follow-up period
	t1	t2 (2 weeks postbaseline)	t3 (4 weeks postbaseline)	t4 (8 weeks postbaseline)	t5 (12 weeks postbaseline)
Enrolment
Recruitment	×
Inclusion/exclusion criteria	×
Informed consent	×
Randomisation	×
Demographic characteristics	×
Medical history	×
Interventions
MA
CA
SA
Assessments
PSQI	×	×	×	×	×
Actigraphy	×	×	×	×	×
Sleep diary	×			×	×
I-TCMS	×	×	×	×	×
HAM-A	×	×	×	×	×
MIV	×	×	×	×	×
AE		×	×
Blinding assessment			×
Treatment compliance			×

t, time point of visit

AE, adverse events; CA, conventional acupuncture; HAM-A, Hamilton Rating Scale for Anxiety; I-TCMS, Insomnia Traditional Chinese Medicine Symptom Scale; MA, meridian differentiation acupuncture; MIV, meridian imbalance value; PSQI, Pittsburgh Sleep Quality Index; SA, sham acupuncture.

Sample size

The sample size was calculated using PASS software (Multiple Comparisons (Test Version)) with the PSQI total score as the primary outcome indicator. Based on the results of the preliminary pretest,⁴³ the mean±SD of the MA group was 7±2.72, that of the CA group was 8±2.42 and that of the SA group was 12.9±1.80. The hypothesised power of the test was 0.9, with α=0.05, and the expected loss of visit rate was 10%. This calculation resulted in a total sample size of 489 individuals for this trial.

Recruitment

Recruitment for the trial will commence in May 2024 and will continue until the required sample size is achieved. Advertisements for recruitment will be disseminated through a hybrid approach, both online and offline. Online postings will be made on various social media platforms, while posters will be displayed in the hospitals involved in the study and their surrounding communities. These recruitment materials will outline the basic inclusion criteria and provide the contact information of the principal investigator for prospective participants to reach out. Initial screening will be conducted online using the PSQI questionnaire, and individuals meeting the subject criteria will undergo formal screening offline.

Randomisation and allocation concealment

Patients eligible for enrolment were registered in the electronic data capture (EDC) system by clinicians at each centre. The random grouping and allocation were performed automatically by the system, which randomly assigned patients to the three groups of this trial in a 1:1:1 ratio. Only clinicians had access to the allocation scheme during this process.

Blinding

Patients will be blinded, and each subcentre will use a separate clinic to prevent patient contact. Meridian testing will be conducted in all three groups to minimise subjective bias, and the blinding assessment will occur at the end of treatment. The statistician will not be informed of the specific groupings and will only refer to them as Group A, Group B and Group C. The principal investigator will not be responsible for the data analysis and will remain unaware of the allocation until the end of the data analysis.

Data collection, management and statistical methods

All the raw data will be collected and stored in the archive of the acupuncture discipline of Henan University of Traditional Chinese Medicine, which is managed by specialised personnel to ensure patient data safety. A statistical analysis plan will be developed by the statistician and the researcher according to the trial protocol. Statistical analysis will be conducted using SPSS V.20.0 software, employing the principle of intention-to-treat analysis for all subjects’ data. Missing data will be filled in using multiple imputation methods. Statistical significance will be set at p<0.05 for all tests. Measurement data will be described by calculating the mean, SD, median, lower quartile (Q1) and upper quartile (Q3). Categorical indicators will be described by the number of cases and percentages of each category. Repeated measures analysis of variance (ANOVA) will be used for multiple time points if the measured information follows a normal distribution, while between-group comparisons will be analysed using one-way ANOVA with multiple comparisons (SNK-q). Generalised estimating equations will be used for multiple time points with non-normally distributed measures, and rank-sum tests will be used for between-group comparisons and hierarchical data. The χ² test or Fisher’s exact test will be applied for categorical indicators. Correlation analyses (latency to fall asleep, total sleep time, number of nocturnal awakenings, duration of nocturnal awakenings, etc) will be performed on MIVs at week 4 and objective sleep data, with Pearson’s correlation for normally distributed data, and Spearman’s rank correlation for non-normally distributed data. A general linear model was used for the primary outcome to evaluate the central effect. Safety analysis will involve describing adverse events (AEs) and reactions, listing their causes and explanations, and calculating the incidence of AEs.

Data monitoring and quality control

To ensure the study’s quality, a special clinical training meeting will be held before the official launch of the clinical trial. This meeting aims to provide uniform training for clinical researchers. Focused training will be conducted on the subject implementation programme and various operational standard operating procedures. The goal is to familiarise each clinical researcher with the research process and specific implementation details related to their responsibilities. This approach aims to improve the interobserver consistency of the researchers, thereby ensuring the reliability of the conclusions of the clinical study. A supervisory team, established by the trial sponsor, the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, will oversee and manage the trial. Their responsibilities include assessing and recording the quality of trial implementation, such as enrolment, the implementation process and the completion of case report forms. Notably, the project sponsor will not be involved in any part of the trial implementation process. All AEs will be reported to the supervisory group and the ethics committee of each centre and will be included in the final study.

Harms

AEs will be monitored during treatment through patient reports and medical staff assessments. AEs may include needle shock, stuck needle, bent needle, broken needle and acupuncture-induced haematoma. Any occurrence of the above should be promptly treated and documented. Common AEs and corresponding countermeasures are described in the online supplemental material table S1. If a serious adverse reaction occurs, resulting in disability, posing a threat to life or causing death, the trial should be halted immediately. Emergency measures should be taken to actively rescue the patient, stabilise vital signs and promptly report the incident to relevant regulatory authorities.

Patient and public involvement statement

None.

Ethics and dissemination

The study protocol has been approved by the Ethics Committee of the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine (2024HL-002) and the ethics committees of other participating institutions. Each participant must provide their signed informed consent form before enrolling in this study, and consent can be withdrawn at any stage. The template of the informed consent form can be found in the online supplemental material. Patients experiencing AEs related to needling will receive free treatment, and the sham-needling group will receive free compensatory treatment at the end of the trial cycle. Upon completion of the study, the results will be published in a journal or made available by contacting the corresponding author via email.

Protocol amendments

If any modifications to the study protocol are needed, they must be decided upon and reported to the trial sponsor for approval, following joint deliberation by the study team. Upon approval, the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine will be responsible for updating the registration information with the China Clinical Trial Registration Center, ensuring that all modified details are recorded. The principal investigator will then notify the subcentres to update the protocol and document the changes with the ethics committee of the respective unit where the subcentres are located.

Trial status

This trial is currently recruiting participants. The study started in May 2024 and is planned to end in December 2027.

Discussion

Because the definition of intractable insomnia lacks clarity and consistency in diagnostic criteria, most clinical studies in mainland China currently define it as insomnia lasting 6 months or more.⁴⁴,⁴⁶ However, this definition only considers the duration of the disease and does not fully capture its treatment-resistant nature. Therefore, we have added the criterion of ineffectiveness after treatment with CBT and medication. We will focus solely on primary intractable insomnia, excluding states of intractable insomnia arising from other sleep disorders (eg, restless legs syndrome)⁴⁷ and insomnia secondary to other diseases (eg, cancer-related insomnia).⁴⁸ Given the complexity of recalcitrant insomnia, a comprehensive understanding of the patient’s sleep status is necessary. The PSQI assesses various symptoms of insomnia and other sleep disorders,⁴⁹ facilitating the evaluation of sleep quality and initial screening for other sleep disorders.⁵⁰ Actigraphy was used to enhance result credibility by objectively recording changes in various sleep indicators, and to further validate the feasibility of MA based on objective data by analysing the connection between objective sleep data and meridian data. However, due to trial limitations, the complete observation cycle of the subjects could not be continuously measured via actigraphy, so measurements were limited to three consecutive days at each visit. Daily sleep diaries were recorded throughout the treatment cycle to dynamically track the efficacy of acupuncture for intractable insomnia. The recording of sleep diaries at baseline and during follow-up periods assisted in the actigraphy measurements. The HAM-A scale, an important tool for the clinical diagnosis of anxiety severity,⁵¹ will be used to observe improvements in anxiety among patients with recalcitrant insomnia.

In this study protocol, the ‘Tiaowei Jiannao’ acupoint group (comprising GV 20, EX-HN 1, BL 62 and KI 6) was selected as the foundational acupoints for the MA group and as the therapeutic acupoints for the CA group. This acupoint group has been validated as effective for treating insomnia through preliminary clinical studies conducted by our team.⁵² Research has indicated that acupuncture at BL 62 and KI 6 can enhance sleep quality by upregulating GABA expression⁵³ in the hypothalamus and the expression of Per 1 and Per 2 mRNAs⁵⁴ in the suprachiasmatic nucleus. Acupuncture at GV 20 and EX-HN 1 can stimulate the synthesis and release of amino acid neurotransmitters, thereby prolonging sleep duration and improving sleep quality.⁵⁵ In this study, we employed this acupoint group as a positive control to validate the efficacy of meridian differentiation. For SA, we used a non-penetrating flat-tipped needle for placebo control. The appearance and operation of the needle were identical to those of real acupuncture, effectively minimising subjective and specific acupuncture effects.

The trial will use a third-party EDC system for randomised grouping and data management throughout the trial, ensuring the concealed nature of allocation. All data entry and modifications will be logged for traceability. Additionally, a supervisory and management team will conduct regular reviews and audits of the data to ensure its authenticity and traceability. This trial aims to validate the efficacy and benefits of MA treatment using objective data.

Limitations

This study has several limitations. First, the study population was restricted to adults, omitting children, elderly individuals and other special populations. Second, due to the nature of acupuncture procedures, blinding was feasible only for patients and not for operators. However, to mitigate subjective bias, researchers, operators and statistical analysts were kept separate. Third, all research centres were located in Henan Province, potentially introducing geographical bias.