This study followed the standard protocol items of the Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) statement. The detailed methods of this study have been reported previously .
This study was a prospective, outcome assessor-blinded, multicenter, randomized, controlled trial with a 1:1 allocation ratio. Participants (n = 20 from each of the three centers) who met the inclusion criteria were randomly allocated to either the acupuncture group (n = 10 from each of the three centers) or AcuKT group (n = 10 from each of the three centers). Both groups received acupuncture treatment once daily, 5 days per week (excluding Saturday and Sunday) for 1 week, and the AcuKT group also received the ankle meridian tendino-musculature and eight-shape form of KT treatment. Outcome measures were determined at baseline (Week 0), 1 week after the first intervention (Week 1), and 4 weeks after completion of the intervention (Week 5). The number of recurrent ankle sprains was determined at 4, 8, 12, and 26 weeks after the completion of the intervention. The study design is summarized in Fig. 1.
Fig.1. Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement.
The figure shows the enrollment, interventions, and data collection protocols.
This study was conducted in accordance with the Declaration of Helsinki and the protocol of this study (ver.1.0) was approved by the Institutional Review Board (IRB) of DongShin University Gwangju Korean Medicine Hospital (DSGOH–039; approval date: March 20, 2017), DongShin University Mokpo Oriental Hospital (DSMOH–002; approval date: March 27, 2017), and KyungHee Korean Medicine Hospital (KOMCIRB–161014-HR–057; approval date: April 28, 2017) before the trial began. This trial was registered at the Clinical Research Information Service (cris.nih.go.kr; registration number: KCT0002257; registration date: February 27, 2017). The purpose and potential risks of this study were fully explained to the participants. All participants provided written informed consent before participating in this study.
Participants were recruited at three hospitals in the Republic of Korea as follows: DongShin University Gwangju Korean Medicine Hospital, DongShin University Mokpo Oriental Hospital, and KyungHee Korean Medicine Hospital. This study was publicized via local newspapers, the internet, and posters in communities and hospitals. The clinical research coordinator continuously monitored the medical conditions of enrolled participants to maximize adherence to intervention protocols.
Patients aged >19 years; (2) those who had sustained a Grade I or II ALAS within the past 7 days; and (3) those who voluntarily signed the informed consent form were included in the study. Grade I ankle sprain was defined as no loss of function, no ligamentous laxity (i.e., negative anterior drawer and talar tilt tests), little or no hemorrhaging, no point tenderness, total ankle motion reduced by ≤5°, and swelling of ≤0.5 cm. Some loss of function, a positive anterior drawer test (anterior talofibular ligament involvement), a negative talar tilt test (no calcaneofibular ligament involvement), hemorrhaging, point tenderness, decreased total ankle motion by >5° but <10°, and swelling of >0.5 cm but <2.0 cm were characteristics of Grade II ankle sprain .
Subjects whose general condition was unsatisfactory or who were unfit for acupuncture or AcuKT therapies were excluded. The detailed exclusion criteria were as follows: (1) fracture as confirmed by radiography, or a Grade III ankle sprain; near-total loss of function, positive anterior drawer and talar tilt tests, hemorrhaging, extreme point tenderness, total ankle motion reduction by >10°, or swelling >2.0 cm (considered to as Grade III ankle sprain) ; (2) history of fracture in the same ankle during the previous year; (3) a wound or skin disease at the KT attachment site; (4) serious disease (e.g., cancer, kidney disease, liver disease, disease of central nervous system, dementia, blood clotting disturbance such as hemophilia, etc.); (5) motor or sensory disturbance caused by a nervous system disorder in the leg with the sprain; and (6) pregnancy or breastfeeding.
Randomization and blinding
After baseline measurements were obtained, SPSS version 20.0 (SPSS Inc., Chicago, IL, USA) was used to assign a serial number to the 60 research volunteers and to randomly allocate 30 of them to each group. The serial number codes were inserted into opaque envelopes that were sealed and kept in a double-locked cabinet, and opened in the presence of the patient and a guardian.
We could only adopt a single outcome assessor-blinding approach because sham treatment was impossible due to the characteristics of KT application, which included attachment to the skin. During the study, the assessor was blinded to group assignments, and data analysts without conflicts of interest were involved in this study.
A clinical research coordinator generated the allocation sequence, enrolled the participants, and assigned participants to interventions.
Acupuncture treatment was conducted as follows: Only sterile, stainless, disposable acupuncture needles (size 0.25×30 mm; Dong Bang Acupuncture, Inc., Boryeong, Republic of Korea; product no. A84010.02) with guide-tubes were vertically inserted into ST36, ST41, BL60, BL62, KI3, KI6, GB39, and GB40 acupuncture points on the affected side . The depth of insertion was 10 to 20 mm, depending on the location of the needle . After insertion, the needles were left in position for 15 min in every session. Manual stimulation and electroacupuncture were not applied.
KT treatment was conducted after acupuncture treatment by the same practitioner. The KT treatment method was conducted as follows. First, an I-shaped tape was applied from ST42 to ST36 over the tibialis anterior muscle (Fig. 2①–③). Second, an I-shaped tape was applied from GB42 to GB34 over the peroneus longus and brevis muscles (Fig.2④–⑥). Third, an I-shaped tape was applied from the abductor digiti minimi muscle and was wrapped around the ankle in a figure-of-eight shape to the abductor halluces muscle, covering both the medial and lateral malleoli (Fig.2⑦–⑨).The NK–50 kinesiology tape was used (width 50 mm, thickness 0.5 mm; Nitto Denko Medical MFG. Co., Ltd., Miyagi, Japan; product no. B07090.02). The tape was laid on the skin without being stretched, to prevent skin problems. The KT treatment was applied daily after the removal of the tape applied the previous day, even in cases in which the patient did not complain of itchiness .
Fig.2. Application of Kinesiotape.
The primary outcome was the visual analog scale (VAS) score for pain, and the secondary outcomes were Foot and Ankle Outcome Scores (FAOS), edema, European Quality of Life Five-Dimension-Five-Level Scale (EQ–5D–5L) scores, and the number of recurrent ankle sprains. VAS, FAOS, and edema measurements were performed at baseline (Week 0; before intervention), 5 days after the first intervention (Week 1; at the end of the intervention), and 4 weeks after the completion of the intervention (Week 5). EQ–5D–5L measurements were conducted at baseline, 5 days after the first intervention, 4 weeks after the completion of intervention, and 26 weeks after the completion of intervention (Week 27). The numbers of recurrent ankle sprains were assessed at 4(Week 5),8(Week 9),12(Week 13), and 26 weeks after the completion of the intervention.
The primary outcome was change in pain severity measured using VAS-pain. The VAS is a 10-cm-long straight line marked at each end with the anchor labels “no pain” and “pain as bad as it could be” . Participants were asked to mark on the line at a point representing the severity of their pain. Scores were recorded in millimeters, with a total score range of 0–100 mm .
The FAOS is a region-specific instrument that is intended to evaluate symptoms and functional limitation in individuals with generalized foot and ankle disorders. It is composed of the following five subscales: pain (9 items), other symptoms (7 items), activities of daily living (17 items), sports and recreational activities (5 items), and foot and ankle-related quality of life (4 items). The subscales are scored separately using a Likert response format, with higher scores indicating higher levels of function .
Edema was measured in centimeters via the figure-of-eight method. The measuring tape was applied across the following landmarks in a figure-of-eight fashion as follows: (1) navicular tuberosity; (2) distal tip of the lateral malleolus; (3) distal tip of the medial malleolus; and (4) base of the fifth metatarsal. The resulting value was compared with the corresponding value for the healthy ankle .
The EQ–5D is a generic instrument for assessing health-related quality of life. It is based on a descriptive system that defines health in terms of five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has three response categories corresponding to no problems, some problems, and extreme problems. The EQ–5D–5L is a new version of EQ–5D that includes five levels of severity in each of the existing five EQ–5D dimensions .
Ankle sprain recurrence was defined as an ankle sprain occurring as a result of sports participation or other daily activities, and which caused one or more of the following: (1) stoppage of the sports activity; (2) limited participation in the next planned sports activity; (3) inability to go to work/school the next day; or (4) the need for medical attention (ranging from onsite care administered by a general practitioner to personal care administered by a sports physician) .
Sample size calculation
In accordance with a previous study , we established the number of groups as two and the effect size as 0.906, with a one-sided alpha level of 0.025 and a statistical power of 0.8. Based on these parameters, the required sample size was 42 (21 per group). Estimating a maximum dropout rate of 30%, we determined that a total of 60 participants were required. The sample size calculation was detailed in our study protocol .
With the approval of the IRB, the statistical analysis was revised from the study protocol. We performed per-protocol analyses for the assessment of efficacy and a supplementary full analysis set. Missing values were implemented by the last observation carried forward method. We compared the results of PP analyses and analyses of the FA set. If there was a significant difference between the PP and FA groups, the cause was reviewed and reflected during efficacy assessment. Analysis was performed by blinded biostatisticians with SPSS version 20.0 software (SPSS Inc., Chicago, IL, USA) using two-sided significance tests with a 5% significance level. Continuous variables are presented as means and standard deviations (SD), and categorical variables are presented as count frequencies and percentages.
Baseline data were collected and compared using the independent t-test, χ2 test, and Fisher’s exact test. Differences between all outcome value changes in the two groups were compared via Wilcoxon signed-rank test and repeated measures ANOVA (Friedman tests). Values of VAS, edema, EQ–5D–5L, and FAOS were compared by repeated-measures analysis of variance (ANOVA) across two to three testing time points (Week 0, Week 1, and Week 5). Differences between two groups of outcome value changes (Week 0 vs. Week 1 and Week 0 vs. Week 5) were compared via the Mann–Whitney U-test (nonparametric test). Differences between two groups in terms of number of recurrent ankle sprains (Week 5, Week 9, Week 13, and Week 27) were compared by the Mann–Whitney U-test (nonparametric test). In accordance with the severity of ankle sprain, participants were divided into Grade I and Grade II groups. A subanalysis was conducted to investigate the differences in changes in VAS, edema, EQ–5D–5L, and FAOS (Week 0 vs. Week 1 and Week 0 vs. Week 5) between the two groups in the Grade I and Grade II group.