|Year : 2016 | Volume
| Issue : 1 | Page : 25-31
Chinese medicine packet plus wax therapy for periarthritis of the shoulder: study protocol for a multi-center, randomized controlled trial
Rehabilitation Center, the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, China
|Date of Web Publication||5-Apr-2016|
Rehabilitation Center, the First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province
Source of Support: None, Conflict of Interest: None
Background: Periarthritis of the shoulder clinically manifests as pain and functional disorder of the shoulder joint. Although there is a tendency to self-heal, results are unsatisfactory. Nonsurgical treatments often used for clinical treatment of periarthritis, including simple closure, massage and acupuncture, do not improve symptoms. Chinese medicine packets and wax treatment effectively improves the local micro-circulation and regulates body functions. Therefore, this study aims to develop a new Chinese medicine wax treatment for periarthritis of the shoulder using these two techniques, and to observe its safety and efficacy.
Methods/Design: A prospective, multi-center randomized, double-blind, placebo-controlled clinical trial will enroll patients with periarthritis of the shoulder who will be randomized into treatment and control groups. In the treatment group, packets will be immersed in a decoction of Chinese medicine. Prepared packets will be placed onto the shoulder joint followed by warm paraffin cake, once a day for 20 minutes, for 4 weeks. In the control group, Chinese medicine packets will be replaced by placebo; all other procedures will be identical. Outcome measures will be assessed at baseline and 1, 2, and 4 weeks after treatment. Primary outcome is the McGill Pain Questionnaire score. Secondary outcomes include shoulder disability questionnaire score, Oxford shoulder score, American Shoulder and Elbow Surgeons score, University of California, Los Angeles shoulder score, the efficacy in treating Traditional Chinese Medicine syndromes, visual analog scale score, and Constant-Murley shoulder score.
Discussion: This trial will provide a quantitative basis to establish therapeutic guidelines and technical standards for Chinese medicine packet plus wax therapy for the treatment of periarthritis of the shoulder.
Trial registration: Chictr.org.cn identifier: ChiCTR-IOR-15006149; registered on 11 March 2015. Written approval for this protocol was obtained from the Ethics Committee of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine in China (approval No. 2014ZX (KT)-010-02).
Keywords: clinical trial; periarthritis of shoulder; wind-cold-dampness; Chinese medicine packet; wax therapy; pain; function of the shoulder; multi-center randomized double-blind controlled trial
|How to cite this article:|
Wang Y. Chinese medicine packet plus wax therapy for periarthritis of the shoulder: study protocol for a multi-center, randomized controlled trial. Clin Trials Degener Dis 2016;1:25-31
|How to cite this URL:|
Wang Y. Chinese medicine packet plus wax therapy for periarthritis of the shoulder: study protocol for a multi-center, randomized controlled trial. Clin Trials Degener Dis [serial online] 2016 [cited 2019 Jun 26];1:25-31. Available from: http://www.clinicaltdd.com/text.asp?2016/1/1/25/179744
Conflicts of interest
YW conceived and designed the trial procedure, wrote the paper, read and approved the final version of the paper for publication.
This paper was screened twice using CrossCheck to verify originality before publication.
This paper was double-blinded and stringently reviewed by international expert reviewers.
| Background|| |
Periarthritis of the shoulder is a chronic degenerative disease involving a variety of soft tissues around the shoulder joint, and is characterized by diffuse shoulder pain and movement disorder (China Association of Chinese Medicine, 2013). Its incidence rate is 3-5% (Manske and Prohaska, 2008). Periarthritis of the shoulder is an aseptic inflammation (Ji et al., 2015), and presents with congestion, edema, inflammatory exudate, tissue thickening, muscle spasms in the early stages, and then bone tissue atrophy, adhesions and spasms of the joint capsule and synovial bursa as well as limited motion because of long-term joint disuse and reduced local metabolism (Neviaser, 1980; Lee et al., 2003; Neviaser and Neviaser, 2011; Yoon et al., 2015). Degenerative changes in the shoulder joint and surrounding muscles often cause shoulder pain. Consequently, patients are unwilling to perform activities, and over time they suffer from muscle stiffness (Buchbinder et al., 2004; Neviaser and Neviaser, 2011). Although there is a tendency for self-healing, it is often unsatisfactory in patients with periarthritis of the shoulder (Reeves, 1975; Rizk and Pinals, 1982; Shaffer et al., 1992). Therefore, it is necessary to develop a therapeutic method to promote the full recovery of shoulder function and reduce sequelae in patients with periarthritis of the shoulder.
The theory of Traditional Chinese Medicine (TCM) states that periarthritis of the shoulder is caused by chronic strain and wind-cold-dampness, and has three types: wind-cold-dampness, stasis and deficiency of qi and blood (Li et al., 2014). Damage to the meridians of the shoulder cause stagnancy of qi and blood stasis, which is a morbid condition manifested as severe localized pain and formation of mass or slough. Therefore, an appropriate therapy is to promote blood circulation by removing blood stasis and activating collaterals at relieve pain. Unfortunately, simple closure, massageor acupuncture cannot effectively relieve adhesions and contractures of the joint capsule and synovial bursa (Huang, 2004; Ma et al., 2005; Xiong and Wei, 2009; Xia, 2012). The Chinese medicine packet is a hop-pocket containing Chinese herbs that activate meridians to stop pain, promote blood circulation by removing blood stasis, warm meridians to promote blood circulation, dispel cold and relieve arthralgia, which can be heated and placed directly on the affected area to improve local blood circulation, accelerate absorption of inflammatory exudates, increase local nutrition, and relieve muscle atrophy (Gu and Guo, 2012; Huang et al., 2013). Wax therapy is a therapeutic method using paraffin wax as the raw material. Because of its high thermal capacity, low thermal conductivity and long cooling time, paraffin wax is a good medium for hyperthermia conduction when in close contact with the body. Clinically, wax therapy is commonly used in the treatment of wind-cold-dampness-induced pain (Dong et al., 2009; Meng et al., 2010; Zhou et al., 2012). When paraffin wax is heated and externally applied to an affected area, it heats local tissues, dilates blood vessels, promotes blood circulation and increases cell permeability. Because of the long duration of heat therapy, it has deep edema dissipation, anti-inflammation and analgesia effects (Dong et al., 2009; Meng et al., 2010; Zhou et al., 2012).
We will develop a new Chinese medicine therapy for periarthritis of the shoulder by combining Chinese medicine packets and wax therapy. This combined therapy will be tested to determine whether it can reduce pain-inducing factors, eliminate inflammation and delay joint aging. The study will be a multi-center randomized double-blind placebo-controlled trial to evaluate quantitatively the safety and effectiveness of Chinese medicine wax therapy for periarthritis of the shoulder.
| Methods/Design|| |
This is a prospective, multi-center, randomized, double-blind, placebo-controlled trial ([Figure 1]).
This study will be conducted at the Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, China; Chinese Medicine Hospital of Fuxin City, China; Orthopedics Hospital of Haicheng City, China; and Affiliated Hospital of Liaoning University of TCM, China.
Ethical review and informed consent
The study protocol follows the Declaration of Helsinki and has been approved by the Ethics Committee of the Affiliated Hospital of Liaoning University of TCM, China (approval No. 2014ZX(KT)-010-02). Any study modification will be approved by the Ethics Committee of the Affiliated Hospital of Liaoning University of TCM, China. Investigators or investigator-authorized officers will be responsible for explaining the objective, content, study procedures, benefits and risks of participating in the clinical trial to each patient or the patient's legal representative. Written informed consent will be obtained from all patients before the trial.
Recruitment of patients with periarthritis of the shoulder is ongoing according to the principle of voluntary participation, through television, radio, newspapers, community and hospital outlets.
- In accordance with the Western diagnostic criteria for periarthritis of the shoulder (Hanchard et al., 2011, 2012; Lewis, 2015)
- Wind-cold-dampness type (State Administration of TCM of China, 1994)
- Aged 40-70 years
- Either gender
- Written informed consent to undergo the therapeutic regimen
- Approval by the Ethics Committee of the Affiliated Hospital of Liaoning University of TCM
- Ages < 40 years or > 70 years
- Acute soft tissue injuries, fractures, or dislocation of shoulder
- Cervical spondylosis, rheumatoid arthritis or gout
- Patients with complications including severe heart failure; severe primary diseases of the lung, liver, kidney, hematopoietic system and endocrine system; cancer; gastrointestinal bleeding; stomach ulcers; bleeding tendencies
- Patients with neuropathy, mental illness, illiteracy or poor compliance who cannot complete the questionnaire in the screening process
- Lactating and pregnant women or women who are preparing to conceive
- Patients who cannot take medicine as directed, and have poor compliance
- Allergic constitution
- Patients who are participating or have participated in other clinical trials within 1 month before the present trial
- Pain caused by cancer or infections
- Dislocation, fractures, osteomyelitis, tuberculosis, cancer and severe osteoporosis reveled by X-ray examination
The patients in this study may be discontinued if one of the following occurs:
- Dissatisfaction with the therapy
- Intolerance to adverse reactions
- Allergic reactions or serious adverse events
- Symptoms aggravated (the subjects need to take other drugs or other therapeutic options)
- Presence of complications or special physiological changes that will disturb the judgement of therapeutic efficacy and safety
- On the request of a regulatory agency
Random allocation sequences for each patient will be generated by SAS 9.0 software that will be input into the central stochastic system of the Clinical Assessment Center, China Academy of Chinese Medicine Sciences, China. A study secretary who cannot directly participate in the clinical trial is responsible for screening patients who have provided written informed consent and applies for random numbers online or by telephone. Patients will be equally randomized into test and control groups. The patients will be treated strictly in accordance with the randomized numbers.
Treatmeat group: Ramulus Mori (30 g), frankincense (15 g), myrrh (15 g), Ramulus cinnamomi (30 g), Natrii Sulfas (10 g), Radix Achyranthis Bidentatae (20 g), Flos Carthami (30 g), Herba Lycopodii (30 g), Caulis Impatientis (30 g), Cortex Erythrinae (20 g), Rhizoma Corydalis (30 g), Radix Angelicae Dahuricae (30 g), Radix Saposhnikoviae (20 g) and Radix Clematdis (30 g), provided by the Affiliated Hospital of Liaoning University of TCM, China, will be ground, soaked in water for 30 minutes, and boiled for 15 minutes to separate the decoction. The above-mentioned procedures will be repeated three times. Decoctions are separated, merged, concentrated and heated to 45-55°C. A gauze packet is then immersed in the prepared decoction for 10-20 minutes. These procedures will be completed at the Drug Manufacturing Room of the Affiliated Hospital of Liaoning University of TCM, China. The prepared Chinese medicine packet will be placed onto the shoulder joint followed by a warm paraffin cake (2-4 cm × 20 cm × 30 cm, 45-55°C) as a hot compress, fixed with a cotton pad, once a day for 20 minutes, totally for 4 weeks.
Control group: Chinese medicine packets will be replaced by Chinese medicine placebo containing food coloring and essence (provided by the Drug Manufacturing Room of the Affiliated Hospital of Liaoning University of TCM). All other procedures will be identical to the test group.
Blinding and unblinding
Both researchers and subjects will be unaware of the grouping. Subjects will be issued with the drugs in accordance with the order number by a drug manager, who is blinded to the randomization information. Data collection and data analysis will be conducted blindly.
The drugs are packaged as required by a drug provider. Drug numbering will be completed by an independent statistical institute, and then sent to different test centers. The remaining drugs will be recovered uniformly at the end of the test. Drug number and emergency unblinding rules will be printed on the group assignment envelope, which will be opaque. If the envelope is opened in an emergency, the opening person, date and reasons for the emergency break will be recorded in the medical record. The envelope contains the subject's medication information, setting and address. The group assignment envelope will be sent to different centers and recovered at the end of the test. All drug encoding processes including the blind record will be written into a file and saved as a clinical trial document. All blinding codes, initial random numbers, and block length will be sealed and saved in duplicate at the Scientific Research Office, the Affiliated Hospital of Liaoning University of TCM and the statistical institution. During the trial, the blinding codes cannot be exposed. If the blinding codes are revealed to impact the test objectivity, the trial will be regarded as invalid. The drug manager will administer the treatment strictly according to the visiting sequence and drug numbering, and the drug number will remain unchanged throughout the testing process.
Random allocation sequences will be stored in the central stochastic system of the Clinical Assessment Center, China Academy of Chinese Medicine Sciences, and revealed at the end of the trial. If severe adverse events occur, which are confirmed to be related to the therapeutic measures by experts in the research institute, the emergency break will be carried out.
Outcome measures will be assessed at baseline and 1, 2, and 4 weeks after treatment.
- McGill pain questionnaire score (Melzack and Torgerson, 1971)
- Shoulder disability questionnaire (van der Heijden et al., 2000)
- Oxford shoulder score (Dawson et al., 1996)
- American Shoulder and Elbow Surgeons (ASES) score (Richards et al., 1994)
- University of California, Los Angeles (UCLA) shoulder score (Amstutz et al., 1981)
- TCM syndromes (including clinical symptoms, signs, tongue, pulse) evaluated using the nimodipine scoring formula with reference to the Clinical Guidelines for New Chinese Herbs, formulated by the Stat Administration of TCM, China (Zheng, 2002) and patient conditions
- Visual analog scale score (Huskisson, 1982)
- Constant-Murley shoulder score (Harvie et al., 2005)
The outcome assessment is shown in [Table 1].
The clinical observation schedule will be completed by the clinical researchers to ensure that the data are accurate, complete, timely, and the original records will be preserved. To ensure real and effective data, the subjects will be asked to specify the date of completion and the time spent to complete a table. A basic questionnaire will be surveyed within 14 days prior to treatment and enrollment information will be completed within the specified date ± 2 days. A data administrator from the statistical institute will be responsible for data entry and management. To ensure the accuracy of the data, two independent data administrators will be in charge of data inputting and proofreading. If there is doubt about the case report form, the data administrators will provide a question table for the researchers. The researchers should answer as soon as possible and return the table. The data administrators can modify, affirm and input the data according to the answers from the researchers. If necessary, the question table will be issued again. At the end of the trial, the established database will be reviewed by the clinical researchers, data administrators and statisticians. After the database is confirmed successfully by blind review, the database will be locked by the major researchers and statisticians, and cannot be modified further.
Sample size calculation
This study is a trial to explore optimal superiority. A one-sided test will be performed, and the number of patients in the two groups will be the same. The effective rates of Chinese medicine packet + wax therapy (t) and Chinese medicine placebo + wax therapy (r) are 0.75 and 0.5, respectively. Therefore, the following parameters will be set: Uα = 1.645 (α = 0.05), Uβ = 0.84 (β = 0.2), P = (0.75 + 0.5) χ 2 = 0.75, Δ = 0.1, N = 2 × (Uα + Uβ) 2 × P (1-P) χ (Pt - Pr-Δ) 2, N = 128.6505 ≈ 130. U is clinical point value; α is the probability of type I error; β is the probability of type II error; P is the combined efficiency; Δ is the minimum difference with clinical significance; N is sample size. There will be 130 cases in the test group and 130 in the control group; therefore, Nr = Nt = 130 (260 in total). Considering loss during the trial (a failure rate of < 15% is allowed), 160 eligible cases of periarthritis of the shoulder in each group will be enrolled. The number of collected cases in different centers is listed in [Table 2].
All data will be statistically analyzed using SAS 9.0 statistical software by the study statistician. The efficacy to treat TCM syndromes will be presented by the case number and percentage, and other data will be expresed by the mean ± SD. Differences at different time points will be analyzed by Radit analysis. Proportionality of baseline data will be analyzed by Fisher's test. Intergroup measurement data will be compared using the homogeneity test of variance. If the data in the two groups are of normal distribution and show homogeneity of variance, a t-test will be performed. If the data are not normally distributed, a rank sum test will be performed. A value of P < 0.05 is considered statistically significant.
Any adverse events reported by patients or detected by physical examination and laboratory tests will be recorded on the case report forms and followed up appropriately. If there are abnormalities by laboratory inspection, the abnormal parameters will be measured at least once a week until they return to normal. To ensure the safety of subjects, necessary measures will be taken immediately when any severe adverse events are reported. In addition, the severe adverse events will be reported to the Ethics Committee, the Affiliated Hospital of Liaoning University of TCM within 24 hours.
| Discussion|| |
Although periarthritis of the shoulder can sometimes heal itself between 6 months and 2 years, pain and inconvenience seriously affect patients' quality of life (Reeves, 1975; Neviaser, 1980; Rizk and Pinals, 1982; Shaffer et al., 1992; Lee et al., 2003; Neviaser and Neviaser, 2011; Yoon et al., 2015). To date, numerous therapies have been reported for the treatment of periarthritis of the shoulder, but there is still no effective therapy with obvious advantages. It is important to develop a safe, highly efficient, and cost-effective therapeutic method with few side effects, to alleviate the suffering of patients and shorten the course of disability (Huang, 2004; Ma et al., 2005; Xiong and Wei, 2009; Xia, 2012). For periarthritis of the shoulder, nonsurgical treatment is preferred with a treatment principle of local analgesia, functional training, and functional recovery of the shoulder joint. In this multi-center, randomized, double-blind controlled trial, Chinese medicine placebo consisting of food coloring and essence will be used as a control. If the Chinese medicine packet plus wax therapy relieves the symptoms of periarthritis of the shoulder, this trial will provide experimental evidence to establish therapeutic guidelines and technical standards for Chinese medicine packet plus wax therapy for the treatment of periarthritis of the shoulder. 
Recruiting is ongoing at submission.
| References|| |
Amstutz HC, Sew Hoy AL, Clarke IC (1981) UCLA anatomic total shoulder arthroplasty. Clin Orthop Relat Res:7-20.
Buchbinder R, Hoving J, Green S, Hall S, Forbes A, Nash P (2004) Short course prednisolone for adhesive capsulitis (frozen shoulder or stiff painful shoulder): a randomised, double blind, placebo controlled trial. Ann Rheum Dis 63:1460-1469.
China Association of Chinese Medicine (2013) Periarthritis of shoulder. Fengshibing yu Guanjieyan 2:73-75.
Dawson J, Fitzpatrick R, Carr A (1996) Questionnaire on the perception of patients about shoulder surgery. J Bone Joint Surg (Br) 78:593-600.
Dong DM, Xing XX, Ren XL, Ma XH, Zhang W (2009) Clinical observation of lumbar discogenic pain treated with paraffin therapy in Chinese medicine. Shijie Zhongxiyi Jiehe Zazhi 4:115-116.
Gu GY, Guo HM (2012) Observation on effect of traditional Chinese medicine packet for adjuvant treatment of patients with acute gouty arthritis. Huli Yanjiu 26:440.
Hanchard NC, Goodchild L, Thompson J, O'Brien T, Davison D, Richardson C (2011) A questionnaire survey of UK physiotherapists on the diagnosis and management of contracted (frozen) shoulder. Physiotherapy 97:115-125.
Hanchard NC, Goodchild L, Thompson J, O'Brien T, Davison D, Richardson C (2012) Evidence-based clinical guidelines for the diagnosis, assessment and physiotherapy management of contracted (frozen) shoulder: quick reference summary. Physiotherapy 98:117-120.
Harvie P, Pollard TC, Chennagiri RJ, Carr AJ (2005) The use of outcome scores in surgery of the shoulder. J Bone Joint Surg Br 87:151-154.
Huang GM (2004) Clinical observation of warming-acupuncture in treating scapulohumeral periarthritis. Guangzhou Zhongyiyao Daxue Xuebao 21:436-438.
Huang Y, Liang ZJ, Liu XF, Lu XJ, Tan LL (2013) Effect of hot application with the packed Chinese medicine in the treatment of patients with diabetic gastroparesis. Qilu Huli Zazhi 19:19-21.
Huskisson EC (1982) Measurement of pain. J Rheumatol 9:768-769.
Ji L, Wang H, Cao Y, Yan P, Jin X, Nie P, Wang C, Li R, Zhang C, Yang M, Yang J (2015) Sharp-hook acupuncture (Feng Gou Zhen) for patients with periarthritis of shoulder: a randomized controlled trial. Evid Based Complement Alternat Med 2015:312309.
Lee MH, Ahn JM, Muhle C, Kim SH, Park JS, Kim SH, Kim SM, Kang HS (2003) Adhesive capsulitis of the shoulder: diagnosis using magnetic resonance arthrography, with arthroscopic findings as the standard. J Comput Assist Tomogr 27:901-906.
Lewis J (2015) Frozen shoulder contracture syndrome - Aetiology, diagnosis and management. Man Ther 20:2-9.
Li ZL, Liu K, Li C (2014) Study and analysis of the clinical efficacy of tuina therapy for different types of shoulder periarthritis. Zhongyi Linchuang Yanjiu 6:24-27.
Ma SY, Cao JB, Chen LX, Mo WH, Bu H (2005) Summary of 178 cases of scapula humeral periarthritis treated by the block therapy and the therapy of Guasha. Gansu Zhongyi 18:17.
Manske RC, Prohaska D (2008) Diagnosis and management of adhesive capsulitis. Curr Rev Musculoskelet Med 1:180-189.
Melzack R, Torgerson WS (1971) On the language of pain. Anesthesiology 34:50-59.
Meng JH, Luo XZ, Luo SH, Xuan PL (2010) Clinical efficacy of acupuncture plis wax therapy in low back pain of osteoporosis. Zhongguo Quanke Yixue 13:2155-2157.
Neviaser AS, Neviaser RJ (2011) Adhesive capsulitis of the shoulder. J Am Acad Orthop Surg 19:536-542.
Neviaser JS (1980) Adhesive capsulitis and the stiff and painful shoulder. Orthop Clin North Am 11:327-331.
Reeves B (1975) The natural history of the frozen shoulder syndrome. Scand J Rheumatol 4:193-196.
Richards RR, An KN, Bigliani LU, Friedman RJ, Gartsman GM, Gristina AG, Iannotti JP, Mow VC, Sidles JA, Zuckerman JD (1994) A standardized method for the assessment of shoulder function. J Shoulder Elbow Surg 3:347-352.
Rizk TE, Pinals RS (1982) Frozen shoulder. Semin Arthritis Rheum 11:440-452.
Shaffer B, Tibone JE, Kerlan RK (1992) Frozen shoulder. A long-term follow-up. J Bone Joint Surg Am 74:738-746.
van der Heijden GJ, Leffers P, Bouter LM (2000) Shoulder disability questionnaire design and responsiveness of a functional status measure. J Clin Epidemiol 53:29-38.
Xia DY (2012) Vacuum sealing drainage: causes of poor drainage and nursing countermeasures. Hulixue Zazhi 27:26-28.
Xiong HR, Wei X (2009) Observations on the efficacy of balancing acupuncture plus painful point injection in treating shoulder periarthritis. Shanghai Zhenjiu Zazhi 28:341-342.
Yoon JP, Chung SW, Lee BJ, Kim HS, Yi JH, Lee HJ, Jeong WJ, Moon SG, Oh KS, Yoon ST (2015) Correlations of magnetic resonance imaging findings with clinical symptom severity and prognosis of frozen shoulder. Knee Surg Sports Traumatol Arthrosc doi: 10.1007/s00167-015-3887-y.
Zheng XY (2002) Clinical Guidelines for New Chinese Herbs. Beijing: China Medical Science Press.
Zhou MW, Wang XP, Liang XY, Li YJ, Guo TF, Li SH (2012) Curative effect of manipulation combined with paraffinotherapy in treating lumbar disc herniation. Xibu Zhongyiyao 25:19-21.
State Administration of Traditional Chinese Medicine, China (1994) Diagnostic Criteria for TCM Syndroms (ZY/T001.1-94).
[Table 1], [Table 2]