Efficacy and safety of combined treatment of miniscalpel acupuncture and non-steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled pilot study

The protocol of this assessor-blinded RCT follows the Declaration of Helsinki and Korean Good Clinical Practice. The study will be conducted at Daegu Oriental Hospital of Daegu Haany University, Daegu, Republic of Korea. Independent researchers blinded to randomization will assess the outcomes and analyze statistics. Informed consent to participate in the clinical trial will be obtained after the researcher provides sufficient information and explanations regarding the study interventions. This protocol follows the SPIRIT guidelines and the checklist and figure are available at the end of the manuscript.

This study is designed as a pilot trial to calculate the appropriate sample size for further RCTs. Each group will include 12 participants, allowing for a 20% dropout rate for evaluating the pragmatic purpose of this trial. A total number of 36 participants will be included, which is larger than the minimum number recommended for pilot studies (Additional files 1 and 2).

One of the main objectives of this study is to provide an estimate of the sample size required for the full-scale clinical RCT. In total, 36 participants with CNP will be recruited through advertisements in local newspapers, on hospital websites, and on bulletin boards. If individuals are interested in participating, they will be invited to the hospital for a screening visit. Eligibility will be determined by one researcher on the basis of the results of physical and radiographic assessments. After completing the screening questionnaire, participants will be guided through the informed consent process. They will be informed about randomization to any one of three treatment groups: MA; NSAIDs; and combined treatment groups. Written informed consent will be obtained from each participant before the initiation of any treatment. After consent forms are obtained, participants will be randomly allocated to one of the three groups in a 1:1:1 ratio (Fig. 1).

Individuals aged 19–75 years who agree to participate after providing written informed consent will be selected as study volunteers. The inclusion criteria are as follows: men or women aged 19–75 years; symptoms such as neck pain and stiffness lasting for ≥ three months; a baseline score of ≥ 4 on the visual analog scale (VAS) for pain; and provision of written informed consent.

Exclusion criteria are as follows: individuals with abnormalities in neurological functions such as cervical nerve function, deep tendon reflexes, and muscle and sensory functions; those with serious sensory or motor disorders requiring surgical treatment; those with a history of spinal surgery or those with procedures scheduled during the study; those with spinal disorders, including vertebral fracture, spinal infection, inflammatory spondylitis, and malignancy, on computed tomography or magnetic resonance imaging; those who are pregnant, planning pregnancy, breast feeding, or refusing to consume certain forms of contraceptives; those with other chronic diseases that can affect the outcomes of the study interventions, including cardiovascular disease, diabetic neuropathy, active hepatitis, fibromyalgia, rheumatoid arthritis, dementia, and epilepsy; those with other severe musculoskeletal problems in areas other than the neck; those with serious psychiatric or psychological disorders; those using aspirin or anticoagulant medications; those using NSAIDs; those with abnormal findings in blood tests for renal or hepatic function; and those deemed ineligible by the recruiting researcher.

The 36 patients will be randomized using simple randomized procedures, with a 1:1:1 allocation ratio. Written informed consent will be obtained before randomization. Random numbers will be generated by an independent statistics professional using SPSS version 19.0 for Windows (release 19.0 K; SPSS Inc. Armonk, NY, USA). Sealed opaque assignment envelopes will be used for allocation concealment. The participants will be allocated into the predefined treatment arms. Allocation concealment will not be broken until study completion. The treatment arm and random number of an individual participant will be recorded in the case report form and randomization table. Outcome assessors and data analysts will be blinded to interventions.

The MA group will receive MA three times over three weeks. The NSAIDs group will be prescribed zaltoprofen 80 mg/Tab (Soleton, CJ Health Care Co., Ltd, Seoul, Republic of Korea) at a dose of one tablet administered orally three times per day over three weeks. The combined treatment group will receive MA and Soleton over three weeks. The prescription will be administered in every visit and drugs that have not been taken will be withdrawn. During the study period, all other interventions such as moxibustion and physical therapy, surgical procedures, and injections for neck pain will be prohibited. Other medications that do not influence neck pain will be allowed. Any change will be recorded at every visit.

The MA points will be as follows [16]: upper site of GV16 (insertion of nuchal ligament, origin of trapezius muscle); GB20; GB12; GV15; BL10; GV14; C4 spinous process (origin of semispinalis capitis); C5 spinous process (origin of semispinalis capitis); and C6 spinous process (origin of semispinalis capitis). A total of 12 sites that appeal to pain will be selected for treatment. The sites can be increased to a maximum of 20 according to the participant’s condition: transverse process of C1 (origin of levator scapulae); transverse process of C2 (origin of levator scapulae and medial scalene); lamina of C5 (2 cm side of spinous process); lamina of C6 (2 cm side of spinous process); and GB21 (Fig. 2). A sterilized, disposable miniscalpel (DongBang Acupuncture Inc., Republic of Korea; 0.5 × 50 mm) will be used. MA will be performed by Korean medical doctors (KMD) licensed by the Ministry of Health and Welfare. The KMD will wear a sterile mask and surgical gloves. After sterile skin preparation, participants will be administered MA at a depth of tendon or ligament level. After treatment completion, the KMD will check for any abnormality and bleeding.

The primary outcome will be measured using VAS. Changes in VAS scores after three weeks of treatment will be measured relative to the baseline scores and will be considered the primary outcome. The secondary outcome will be determined by the Neck Disability Index (NDI), EuroQol 5-dimension (EQ-5D) questionnaire, and Patient Global Impression of Change (PGIC) scale. Outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end point), and 7 (four weeks after treatment completion). Outcome measurements will be recorded by two independent researchers. Table 1 shows the treatment and outcome measurement schedules.

VAS is a 10-cm measurement instrument to determine the severity of pain. A 10-cm horizontal line will be used. The individuals rate his or her pain on a scale of 0–10, where 0 indicates the absence of pain and 10 indicates the worst pain imaginable. Participants will estimate their level of pain by marking on the line. Then the distance from “absence of pain” point will be measured [17, 18]. In this study, the VAS score will indicate pain at the point of measurement. Changes in VAS scores after three weeks of treatment, relative to the baseline scores, will be considered the primary outcome.

The safety of this trial will be assessed by the red blood cell count, hemoglobin level, hematocrit, total white blood cell count, differential count, erythrocyte sedimentation rate, platelet count, aspartate aminotransferase level, alanine aminotransferase level, blood urea nitrogen level, prothrombin time, partial thromboplastin time, C-reactive protein and creatinine levels, serum sodium level, serum potassium level, and serum chloride level. All participants will undergo blood tests twice during the study, once at screening and once at the fourth follow-up visit. Nexina (potassium bismuth citrate 100 mg/Tab, ranitidine hydrochloride 84 mg/Tab, sucralfate hydrate 300 mg/Tab) will be prescribed if the participants complain of dyspepsia symptoms such as nausea, abdominal discomfort, and diarrhea.

All adverse events (AEs) and vital signs will be observed at every visit. Serious AEs (SAEs) will be reported to the IRB. The individuals will be asked to voluntarily report information about AEs and the researchers will confirm the occurrence of AEs through methods such as medical interviews. Details about AEs, such as the date of occurrence, degree of severity, causal relationship with the treatment, other treatments or medications that are suspected to cause the AE, and treatment of the AE, will be reported in detail.

All participants will have the right to withdraw from the study at any time. Participation will be terminated at any stage if the individual refuses to continue, withdraws consent, or violates the inclusion or exclusion criteria. The trial will be stopped if the principal investigator believes that there are unacceptable risks of SAEs.

The results of this study will provide a preliminary report regarding the efficacy and safety of MA treatment combined with NSAIDs for CNP. All statistical analyses will be performed using IBM SPSS version 19.0 for Windows (Release 19.0 K; IBM SPS Inc., Armonk, NY, USA) and will be based on the Statistics Guidelines for Clinical Trials [22]. The significance level of the tests will be set at 0.05. One-way analysis of variance (ANOVA) and descriptive analysis will be performed to compare baseline characteristics between groups. Trends over time and time-by-treatment interactions will be explored using repeated measures ANOVA. The Chi-square test or Fisher’s exact test will be performed to compare differences in ratios caused by AEs between groups.

A qualified clinical research associate will oversee study protocol compliance, informed consent documents, overall progress of the trial, participant recruitment, data quality and timeliness, performance of the interventions, and all fields and process of the trial. If any important protocol modifications or violations exist, an amended protocol will be resubmitted and reported to the relevant parties (e.g. investigators, IRB, trial participants, trial registries, and sponsor).