Observation of Curative Effect on Meridian Theory-based Extracorporeal Shock Wave Therapy for Non-specific Low Back Pain: Study Protocol for a Randomized Controlled Trial

doi:10.21203/rs.3.rs-1528360/v1

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Study protocol

Observation of Curative Effect on Meridian Theory-based Extracorporeal Shock Wave Therapy for Non-specific Low Back Pain: Study Protocol for a Randomized Controlled Trial

https://doi.org/10.21203/rs.3.rs-1528360/v1

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Background

Non-specific low back pain (NLBP) is a major global socioeconomic burden, and the prevalence of NLBP is still on the rise. At present, there is no ideal cure effect of drugs for this disease. This may be the reason why patients often use complementary therapies. Among them, extracorporeal shock wave therapy (ESWT) has gradually received more attention and has become the main treatment method for NLBP. The purpose of this study is to provide scientific evidence for the effect and safety of meridian theory-based ESWT on NLBP.

Objective

This study aims to evaluate the effect and safety of meridian theory-based ESWT on NLBP. This study will also provide more high-quality experimental evidence for the clinical application of meridian theory-based ESWT for the treatment of NLBP in the future.

Methods

This study is a single-blind, multi-center, randomized controlled trial. 64 patients with NLBP, aged 18 to 60 years, will randomly divided into two groups: the experimental group(N.=32), which will receive meridian theory-based ESWT application, and the control group(N.=32) which will receive conventional ESWT treatment. These two applications will be carried out twice a week for two weeks. The primary outcomes will be Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). The secondary outcome will be Surface Electromyography (sEMG). All outcomes will be evaluated at baseline and after the intervention (7 days, 14 days).

Discussion

The results of this multi-center randomised controlled trial will contribute to providing rigorous clinical evidence for the efficacy and security of meridian theory-based ESWT for NLBP.

Trial registration:

Chinese Clinical Trial Registry, ChiCTR2100051049. Registered on 10 September 2021, http://www.chictr.org.cn/showproj.aspx?proj=46316

extracorporeal shock wave therapy(ESWT)

meridian theory

non-specific low back pain(NLBP)

clinical trial

Low back pain is the major cause of dysfunction, affecting all age groups and being more common in adults^{[1, 2]}. At the same time, the prevalence and burden of low back pain increase with aging^[3]. Many patients with low back pain cannot be specifically diagnosed, and approximately 85% of cases cannot be attributed to specific pathological changes or nerve root irritation^[4]; Therefore, most patients with low back pain have NLBP. ^[5]. Pain and dysfunction are common features of NLBP^{[6, 7]}.

At present, most treatments for NLBP have limited efficacy with a high recurrence rate ^[8]. The main purpose of clinical treatment of NLBP is to relieve pain and improve patients’ quality of life. There are many clinical treatments for NLBP, including conservative therapy and surgery^[9–11]. Conservative therapy including bed rest, drug therapy, physical exercise and exercise therapy can relieve NLBP to a certain extent, but there are also many drawbacks; Surgical treatment is accompanied by problems such as postoperative infection and poor long-term efficacy, and the high cost brings a heavy economic burden to patients^[12]. Therefore, there is an urgent need for a safe, effective and economical treatment for NLBP.

Extracorporeal shockwave therapy has been extensively used for the treatment of NLBP in recent years^{[13, 14]}. ESWT is a therapeutic method that applies shock waves to lesions from the inner body to boost blood flow and stimulate or reactivate affected connective tissue (including tendons and bones) to relieve pain and improve dysfunction. ^[15]. Recently, based on meridian theory of TCM, ESWT combined with acupoint stimulation has played a therapeutic role ^[16]. The purpose of this study is to observe the clinical efficacy of meridian theory-based ESWT on pain and dysfunction in NLBP patients.

Study design

This is a single-blind, multi-center, randomized placebo-controlled trial supported by the Henan Provincial Administration of Traditional Chinese Medicine. The trial will be jointly conducted by three centers in Zhengzhou, China: the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, and the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine. Patients between 18 to 60 years with NLBP will be included. When participants are eligible for inclusion after being informed about the purpose and procedures of the study, they will be asked to sign an informed consent form. Then, Sixty-four patients will be recruited and randomly assigned to two groups: the experimental group (N.=32) and the control group (N.=32). Participants in the experimental group will receive ESWT based on meridian theory, and participants of the control group will receive conventional ESWT treatment. Patients will be treated twice a week for two weeks. All the participants will be assessed 3 times: baseline (evaluation before treatment), the middle of the treatment (7 days after treatment starts), and the end of the treatment (14 days after treatment starts). The volunteers will complete the VAS, ODI, and sEMG assessments. The study 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
Timepoint	−1 week	0 week	1 week	2 weeks
Enrolment
Eligibility screen	×
Informed consent	×
Medical history	×
Merger disease	×
Randomization		×
Interventions
Experimental group		×	×		×
Control group		×	×		×
Assessments
VAS		×	×		×
ODI		×	×		×
sEMG		×	×		×
Safety evaluation		×			×
Adverse events		×	×		×

Ethics committee approval

This trial was reviewed by the ethics committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine on August 24, 2021 (reference number: 2021HL-203-01). Written informed consent will be obtained from all participants. The study was registered with Chinese Clinical Trial Registry (Identifier ChiCTR2100051049.)

Participants

Eligible participants will be recruited in China at three hospitals——(the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, and the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine). To recruit participants, three independent centers will publish study advertisements online (webpage) and offline (flyers). The recruitment of participants began on 15 September 2021 and is expected to end in 9 December 2022, or it may be completed earlier if a sufficient number of patients are recruited.

Inclusion criteria

Participants meeting the following criteria will be included:

1. Meeting the diagnostic criteria for NLBP;

2. Male or female patients aged 18–60;

3. Patients with normal intelligence and language skills;

4. Patients with NLBP who had not used any treatment in the past two weeks ;

5. Willingness to be volunteers for the trial and provide informed consent.

Exclusion criteria

Participants who report any of the following condition will be excluded:

1. Patients will be excluded when low back pain is caused by specific pathological factors such as tumors, Osteoporosis, lumbar fractures, rheumatoid arthritis;

2. Patients deemed by researchers as ineligible to participate due to severely abnormal/unstable laboratory test results or vital signs;

3. Patients with other serious diseases such as immune diseases, endocrine diseases, and abnormal liver and kidney functions;

4. ESWT -phobic patients.

Elimination criteria

1. Patients who do not meet the diagnostic criteria for NLBP and are erroneously included;

2. Patients who are judged by the researchers as unsuitable to continue the trial because of serious adverse complications.

Randomization

Participants who are eligible in the screening phase and agree to sign the consent form will be randomly assigned to the experimental group or the control group. The random sequence numbers will be generated through the computer. The allocation will be concealed using consecutively numbered sealed and opaque envelopes. For this, an independent researcher who will not participate in other study procedures will carry out the randomisation process to avoid bias. The allocation sequence will be generated by a specialized statistician who does not participate in this experiment. Relevant independent researchers in three centres will recruit participants who assign participants to two different intervention groups.

Blinding

This is a single-blind study. All other researchers, such as assessors and data analysts, will be unaware of group assignments. To confirm whether participants achieved blinding, assessors will use a "blinding test" questionnaire to ask participants what type of treatment they think they received after the first and final treatment.

Sample size calculation

We will conduct this study in a randomized controlled trial design method, and the main observed outcome is the improvement of patients’ pain. Previously, we conducted a small sample(12 cases) of clinical observation and found that the 1-week experimental group received ESWT with meridian theory-based and the control group received conventional ESWT treatment can reduce the level of the VAS scale by 3.45±1.31 and 2.33±1.13, respectively. The significance test level is 0.05, and the test power is 0.9. The sample size is calculated by using:

N is the required sample size for each group, and the sample size of each group is equal. Where α is 0.05 and β is 0.1, the normal distribution quantile table shows that:

Z_α/2 = 1.96, and Z_β= 1.282.

σ and δ represent the population standard deviation and allowable error, which are 1.31 and 1.12, respectively. By substituting the above data into the formula, it is calculated that 29 cases will be needed in each group. Taking into account the 10% expulsion rate, the final estimated sample size will be about 32 cases in each group (64 in total).

Interventions

The intervention treatment period includes 4 sessions during 2 weeks. Licensed medical doctors who are bothering at least 4 years of clinical experience will perform the intervention. Meanwhile, each patient will receive the same routine therapeutic drug and rehabilitation treatment. The interventions for the two groups are as follows:

Routine Therapeutic Drug Treatment： All patients use blood pressure control, blood lipid adjustment, blood sugar control, and nutritional nerve drug as routine therapeutic drug treatment following the physicians' instruction.

Extracorporeal shock wave intervention： ESWT will be applied by a BTL-5000 pneumatic ballistic ESWT machine, 8.0–10 Hz, 1.6–3.0 bar energy density, 2000 pulses, twice a week for two weeks.

The experimental group： In addition to the routine treatment for patients with low back pain, extracorporeal shock wave therapy will also be performed at Huantiao(GB30), Baihuanshu(BL30), Xiaochangshu(BL27), Pangguangshu(BL28), Guanyuanshu(BL26), Qihaishu(BL24), Dachangshu(BL25), Sanjiaoshu(BL22), Chengfu(BL36), Yaoyan(EX-B7) and Yaoyi (EX-B6) in the experimental group^[17] (Table 2).

Table 2: Locations of acupoints for ESWT

Acupoints	Location
Huantiao(GB30)	In the buttocks region, at the junction of the lateral one third and medial two-thirds of the line connecting the prominence of the greater trochanter with the sacral hiatus.
Baihuanshu(BL30)	In the sacral region, at the same level as the fourth posterior sacral foramen, 1.5 B-cun lateral to the median sacral crest.
Xiaochangshu(BL27)	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.
Pangguangshu(BL28)	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.
Guanyuanshu(BL26)	In the lumbar region, at the same level as the inferior border of the spinous process of the fifth lumbar vertebra (L5), 1.5 B-cun lateral to the posterior median line.
Qihaishu(BL24)	In the lumbar region, at the same level as the inferior border of the spinous process of the third lumbar vertebra (L3), 1.5 B-cun lateral to the posterior median line.
Dachangshu(BL25)	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.
Sanjiaoshu(BL22)	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.
Chengfu(BL36)	In the buttock region, at the midpoint of the gluteal fold.
Yaoyan(EX-B7)	In the lumbar region, au niveau du rebord inferieur du processus epineux L4, lateral a la ligne mediane posterieurede 3, 5 cun.
Yaoyi (EX-B6)	In the lumbar region, au niveau du rebord inferieur du processus epineux L4, lateral a la ligne mediane posterieurede 3 cun.

The control group： Only routine ESWT treatment will be performed for patients with low back pain.

Outcome measures

Primary outcome

Visual Analog Scale (VAS)： Pain intensity was assessed using the VAS^[18]. The reliability and validity of this questionnaire are well established and It has the advantages of simplicity, time savings, convenient operation, and relevance to a wide range of people. The VAS is an 11-point scale ranging from 0 to 10. VAS score of 0 implies the absence of pain, and a score of 10 implies unbearable pain. Many clinical trials for NLBP use VAS as their main outcomes.

Oswestry Disability Index (ODI): The ODI is a simple and comprehensive patient-rated outcome used to assess Lumbar spine dysfunction^[19]. The ODI is used to measure NLBP -related dysfunction and includes 10 questions about daily activities, including pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sexual life, social life, and traveling. The ODI has 6 response categories. Each item scores from 0 (better) to 5 (worst). Each score is transferred into a 0 to 100 scale, with lower scores indicating lesser Lumbar spine dysfunction.

Secondary outcome

Surface Electromyography(sEMG): The secondary outcome is

surface electromyography (sEMG) measurement^[20]. The sEMG evaluation is an objective method to obtain the electromyographic signal during muscle activity, which is achieved by placing surface electrodes on the muscle layer. It can perform a quantitative and qualitative analysis of the function of muscles and can study multiple muscles in the body at the same time. It has the advantages of innovativeness, safety and reliability, convenient operation, and objective quantification.

Data management

CRFs will be truthful, completed, accurate, and timely record all information of participants. All relevant information of participants will be kept strictly confidential. After the trial, the quality control team will strictly review the submitted CRFs and ensure the accuracy and completeness of the CRFs.

Statistical analysis

We intend to apply SPSS V.20 software to the statistical analysis of all results. The CI will be established at 95%, and the significance level at 0.05. Missing data refers to the use of actual observations without imputation when the dropout rate does not exceed 10%. The normality test will be applied to all data first. Then, mean±SD will be used to describe the data that fit the normal distribution; medians and interquartile ranges will be used to represent central and discrete trends in quantitative data that do not fit the normal distribution. The t-test and analysis of variance(ANOVA) will be applied to quantitative data, and the rank-sum test will be applied to count data to compare differences between groups. Sensitivity analysis will be carried out if necessary. P<0.05 will be considered statistically significant.

Quality control

Prior to the trial, all medical workers will accept strict training on related tasks. The therapist in this trial have licenses with at least 4 years of clinical experience. Monitors will inspect case report forms twice every week and patient situations during the treatment period. Dropouts and withdrawals involving the reasons will be documented detailedly during the trial. Participants’ information will be kept strictly secret at the study sites with limited access; Only investigators can view the data. All investigators will always maintain a strict privacy policy to protect confidentiality in the whole process of the trial.

Safety evaluation and adverse events

The whole trial will monitor and report all adverse events (AEs). Any uncomfortable symptom or diseases during this study will be recognized as adverse events, such as localized haematoma, allergies, pain, dizziness, vomiting, or palpitations. The study will detail record AEs —including symptoms, onset and end date, severity, relationship with ESWT, and outcome. Participants will be stopped treating if the treatments cause serious aggravation of symptoms, which increased pain as measured by VAS at the end of the first hour after ESWT. Researchers will immediately report SAEs (eg, requiring hospitalization, causing disability, or impaired ability to work) to the ethics committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine and suspend the study.

The purpose of this study is to evaluate the effectiveness of meridian theory-based ESWT on relieving pain and other symptoms which cause a negative impact on the quality of life in these individuals with NLBP. To do this, the study involves the experimental group and the control group, and interventions will be conducted two times per week for 2 weeks. According to some previous studies^[21], meridian theory-based ESWT can produce a faster and better analgesic effect than conventional ESWT. However, no studies have reported a difference in the effect of these two treatments in patients with NLBP. This trial comparing the two could fill gaps in the literature, thereby assisting physiotherapists and clinicians in clinical decision-making.

The VAS is one of the most commonly used instruments for the assessment of pain and has been validated to detect changes in pain intensity^[22]. The ODI scale is the most widely used dysfunction assessment questionnaire and has the advantages of simplicity, time savings, convenient operation, and relevance to a wide range of people^[23]. Therefore, they have also been used in many studies applying ESWT for NLBP. Moreover, the electromyographic signal measured by an sEMG is well suited for evaluating the effects of ESWT for NLBP^[24]. These will support the main results and be meaningful for the overall effectiveness assessment.

Strengths of the study include its strictly standardized endpoints and objective criteria, strict quality control. The trial also has some limitations. First, this is a multicenter study conducted at three tertiary A hospitals in China and the results might not apply to primary hospitals or other countries. Second, the therapist will not be blinded due to the nature of the study, which might bring bias and influence the results.To achieve our clinical goals, we will strive to standardize every step of this study. We expect that the results of this trial will provide evidence of the efficacy and safety of meridian theory-based ESWT for NLBP. This will provide a practical and effective treatment method for the clinic, which has very important social significance.

ESWT:extracorporeal shock wave therapy; NLBP:non-specific low back pain; VAS:visual analog scale; ODI:Oswestry disability index ; TCM:Traditional Chinese Medicine;sEMG:Surface Electromyography ; CRF: Case report forms.

Acknowledgments

Special thanks to the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine and the Henan Provincial Administration of Traditional Chinese Medicine for their support of this study.

Authors’ Contributions

Yongfu Fan, Feilai Liu and Mengna Li contributed equally to this work. The rest of the authors also made significant contributions and assisted in the completion of the trial.

Funding

This work was supported by the Henan Provincial Administration of Traditional Chinese Medicine. Henan Province Traditional Chinese Medicine Scientific Research Special Project (20-21ZY2176)

Availability of data and materials

Not applicable; no data have yet been generated.

Ethics approval and consent to participate

Competing interests

The research funders are not responsible for study design, data collection and management, and manuscript writing and publishing licenses. Yongfu Fan, Feilai Liu, and Mengna Li are considered co-firstauthors. All authors confirmed the final version of the manuscript. All authors report no conflicts of interest in this work.

Author details

1 Henan University of Chinese Medicine, Zhengzhou 450000, China

2 Rehabilitation Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China

3 Institute of Pain Medicine and Special Environmental Medicine, Nantong University, Nantong 226019, China;

Dissemination policy

After studying consummation, the final data will be submitted by the researcher to the Henan Administration of Traditional Chinese Medicine in the form of a research report. Research results will be published in authoritative journals or presented at high-level academic conference.

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No competing interests reported.

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You are reading this latest preprint version

Observation of Curative Effect on Meridian Theory-based Extracorporeal Shock Wave Therapy for Non-specific Low Back Pain: Study Protocol for a Randomized Controlled Trial

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