Preliminary clinical randomized controlled trial on knee osteoarthritis treated with moxibustion

World JournalofAcupuncture-Moxibustion (WJAM)

Vol. 22, No.2, 30th Jun. 2012

·28·

ELSEVIER

Clinical Research

Preliminary clinical randomized controlled trial on knee osteoarthritis treated with moxibustion * REN Xiu-mei (1£~~i'Z, CAO Jin-jin (t~Jl)r, WANG Li-zhen (.£ m:J>#JJi)r, ZHAO Ling (M..

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SHEN Xue-yong (ijl:~ Jii,313:J, WU Fan (:k JL)r, ZHANG Hai-meng (*~~i

1. Acupuncture-Moxibustion and Massage College, Shanghai University ofTCM, Shanghai 201203, China; 2. Acupuncture and Moxibustion Department, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China; 3. Shanghai Research Center ofAcupuncture and Meridians ( 1. -.t7f!t9='I2:£~:::k~ ftffdt*~~,

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ARTICLE INFO

ABSTRACT

I3:J Correspondingauthor:SHEN Xue-yong

Objective Toobserve the therapeuticeffectof moxibustiononpain, stiffness andphysical dysfunctioncausedby knee osteoarthritis(KOA), andmake an assessmenton the effectivenessandsafety ofthis therapy. Methods Fiftynine cases of KOA were randomlydividedinto a moxibustiongroup(31 cases) anda sham-moxibustiongroup(28 cases). The treatmentof moxibustionwas givenat Neixiyan (I*JJJ*~~ EX-LE 4), Dubf (~. ST35) and Ash; pointswith realmoxa conein the moxibustiongroupand shammoxa conein theshammoxibustiongroup,3 coneson each point per time, onceevery two days,3 timesper weekfor consecutively6weeks.The resultswere recordedin week 3and 6 of the treatment, and the follow-upvisit was performed6weeks after the end of treatment.TheWestern Ontarioand Mcmaster Universities OsteoarthritisIndex(WOMAC) and the shortestwalkingtime of 46m were adoptedto evaluatethe recoverysituationofjointfunction.TheUT-325 digital thermaldetectorwasput touse torecord the temperaturechangein themost obviouspainful pointsof knee jointbeforeand afterthe moxibustion.Results Allthe scoresof WOMACin the moxibustiongroupwere apparentlydecreased inweek 3and 6 of the treatmentaswell as the follow-upvisit, separately (PO.05), andthe between-groupdifferencewas notsignificantstatistically(P>O.05). The temperatureof treatmentpointafter the moxibustionwas(49.81±3.10) 'C in the moxibustiongroup and(40.98±1.67) 'C in the sham-moxibustiongroup, which was both increased apparentlyas compared with that before the treatment (P
(1957-),male, professor. Researchfield:the functional characteristicsof acupointandthe mechanismof moxibustion. E-mail:[email protected]

* Supportedby National973Project: 2009CB 522901;The LeadingAcademic DisciplineProjectofState Administration ofTCM andthe Cityof Shanghai: S30304; The ScientificandTechnological BrainstormProject ofShanghai:11 DZ 1973300,11 ZR1436700. Thispaper was firstlypublishedin Zhongguo Zhenjiu (Chin Acup-Mox,Chin)

inChinese, 2011,12

KEY WORDS: osteoarthritis;knee; moxibustion;randomizedcontrolledtrial (RCT)

World Journal ofAcupuncture-Moxibustion (WJAM)

ELSEVIER

Vol. 22, No.2, 30th Jun. 2012 Table1

Groups

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Comparisonof thegeneral dataof patientswith knee osteoarthritisbetweenthe twogroups

Patients

Sex (cases) Male

Female

Age (years) Youngest

Oldest

Duration of sickness

Mean(X±s)

Shortest (months) Longest (years) Mean (X±s, years)

BMI (X±s)

Moxibustion

31

11

20

55

78

64.03±7.24

6

30

6.82±6.60

24.36±2.90

Sham-moxibustion

28

8

20

47

77

62.57±8.l2

3

30

7.l5±7.72

25.03±3.35

The moxibustion is a treatment mainly using moxa, which has the effect of heating and medication by warm or burn lesion regions and acupoints on the body surface'". As one of the oldest nonpharmaceutical treatment, moxibustion has many indications, simple and convenient application and unique effect in the clinical practice. Other than acupuncture, there is no necessary for moxibustion to puncture the skin or handle special manipulation, which is easy to follow and reduces the differences between different operators in order to have more normalized clinical studies. At present there are many clinical randomized controlled trials on acupuncture, besides, the system reviews and Meta analysis have also shown that the clinical effect of acupuncture is positive'<". However, the clinical research of moxibustion generally have many problems, such as indifference of methodology, lack of research design with exactly randomized controlled standard and no systematic clinical observation, which means standard research system has not yet come into being, as a result, we could not correctly evaluate the effectiveness and security of this traditional treatment. CHEN ken, a senior medical officer in the Western Pacific Region of WHO, said the key of problems that clinical researches at home can't put forward enough evidence to prove the effect of acupuncture and the results can't be admitted by oversea current medicine is that the research method with the modem scientific idea couldn't be accepted and consciously used by our acupuncture clinical researchers'". For this reason, according to the international clinical research method, the authors started a randomized, double-blinded and controlled clinical trial for the treatment of knee osteoarthritis (KOA) with moxibustion. The report is as follows.

CLINICAL DATA General data This trial was approved by Chinese Ethics Committee of Registering Clinical Trials (certificate: ChiECRCT-20110022), and all the patients were enrolled from Outpatient Department of Acupuncture and Moxibustion, Shanghai Pudong New District Hospital of TCM and Orthopedics and Traumatology Department, Shanghai Seamen's Hospital from

September 2009 to October 2010. Sixty-five cases who met the inclusion criteria were admitted and then randomly divided into a moxibustion group (33 cases) and a sham- moxibustion group (32 cases). Of them, 2 cases in the moxibustion group only received the treatment for 3 weeks out of family business; in the sham- moxibustion group, 2 cases dropped the treatment because of the lumbar disc herniation while another 2 cases left for the long distance between home and hospital, and the other 59 cases finished all the treatment of 6 weeks. The general data of sex, age, illness course and body mass index (BMI) showed no significant difference between the two groups (all P>0.05), which indicated the comparability (Table 1).

Diagnostic criteria In reference to the clinical diagnosis of knee osteoarthritis by American College of Rheumatology (ACR) in 1995[7], the standard was as follows: CD Knee pain during most days of a month; ® Osteophyte at the joint margins showed by X-ray; ® In accordance with the diagnosis of knee osteoarthritis on the test of synovial fluid; ® Age> 40; @ Less than 30 min of morning stiffness; @ Crepitus (noisy, grating sound) on active move. The patients were diagnosed as knee osteoarthritis in this trial if

CD®orCD®@@orCD®@@. Inclusive criteria

CD Aged in the range of 45 to 78 years, sex free; Moderate or obvious knee pain during almost every day of last month; ® No treatment of intraarticular injection, acupotomy and acupuncture within 3 months; ® At least one osteophyte showed by X-ray (Kellgren-Lawrence grade e Z); @ Being voluntarily willing to accept the randomized grouping, understand and sign Consent Form.

®

Exclusive criteria

CD Combined with inflammatory joint diseases,

gout, cute knee trauma or other arthritis (with no change of cartilage), meniscus injury, ligament damage and fracture in the joint; ® Complicated with serious disease of heart, kidney and liver, malignant tumor (unless cut and no recurrence within 5 years), systemic infection or infectious diseases, diabetes mellitus without satisfactorily control of blood sugar; ® Being

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World Journal of Acupuncture-Moxibustion (WJAM) Vol. 22, No.2, 30th Jun. 2012

injected with corticosteroid or Hyaluronic acid into the articular cavity (including joint surgery and local medication) in the past three months, received other moxibustion treatment; ④ Not following the require of the treatment though met the diagnosis of knee osteoarthritis.

and bottom of the base, and the inside/outside diameter of the out ring of the buffer plate was the same as that of the bottom base. And there were wafer with many holes in the buffer plate, which was connected to the outside ring with two wings.

Eliminated, drop-off and suspended criteria

When using the real moxa in the moxibustion group, the bottom base was attached to the acupoints, so that the moxa cone could be burned 8 mm above the skin, while in the sham-moxibustion group, the appearance, burning process and residue was the same as the moxibustion group, but the insulation metal membrane in the bottom base could insolate the moxaproduced heat and smoke and prevent them from radiating to the skin. The device was successfully used in trials[8].

① Eliminated criteria: not meeting the criteria after the inclusion or not following require of the trial during the treatment. ② Drop- off criteria: not finishing or quitting the trial, incomplete data, having negative influence on the valuation of curative effect or security, treated with other therapy or medicine to interference the results. ③ Suspended criteria: complicated with severely adverse events or reactions, serious complications during the treatment (serious infection due to blister), which had negative influence on the valuation of curative effect. The eliminated, drop-off and suspended patients were given questionnaire survey when they left the research, severely adverse reactors of which was reported to the Ethics Committee.

Randomizing and trial grouping According to the random digital table that was created by Excel 2003, the patients were divided into a moxibustion group and a sham-moxibustion group, which were marked with different codes respectively. The names of the patients and group codes were recorded and saved. The treatment operators, who only recorded patients’ codes, gave the treatment with the corresponding moxa cone that was also marked with codes. The results were also evaluated by speciallyassigned person. The patients, treatment operators and valuators had no idea of the grouping situation.

METHODS Instrument of moxibustion The novel moxibustion device that was invented by Professor ZHAO Bai-xiao of Beijing University of CM was applied in this research (Figure 1). This pillar included moxa cone and base. The base was cylindrical and had a layer on the top, which could stop the burning. There is buffer plate between the top

Figure 1  The novel self-application moxibustion device

Moxibustion group The real moxa was used in the moxibustion group. Selection of acupoints: Nèixīyǎn (内膝眼 EXLE 4), Dúbí (犊鼻 ST 35) and Ashi points. After locating the points, the device was attached to start the treatment, 3 cones on each point every time, once every two days, 3 times in a week for consecutive 6 weeks, 18 times altogether. If the assignment was missing during the treatment, it must be made up within one week and no prolong the course of the treatment. Allowed times of missed treatment 2, missed treatment＞2 times indicated the withdrawal of the trial.

Sham-moxibustion group Except that the sham-moxa that has the same appearance of real moxa was applied, the other therapy parameters in the sham-moxibustion group were the same as those in the moxibustion group. The patients in the two groups received the treatment separately, and given by different therapy operators, which could prevent from breaking the blinding because of the communication among patients. Each times of treatment was also been supervised by specially-assigned person.

Observation indices (1) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC): 24 questions in all, including 5 pain questions, 2 questions involved with joint stiffness and 17 body function questions. The evaluation of patients’ joint pain could be given according to the VAS from 0 (no pain) to 100 mm (very severe pain). The evaluation was done before the treatment, week 3 and 6 of the treatment as well as

World Journal of Acupuncture-Moxibustion (WJAM) Vol. 22, No.2, 30th Jun. 2012

·31·

Table 2  Comparison of WOMAC score of knee osteoarthritis patients before and after treatment between the two groups Groups

Patients

Indices

Moxibustion

31

Pain Physical function Stiffness

Sham-moxibustion

28

Pain Physical function Stiffness

Before treatment

Week 3

Week 6  1)

Follow-up visit  3) 4)

32.42±16.97 32.07±16.70 37.15±22.73

22.92±14.60 20.26±13.56 2) 24.87±20.39 2)

12.67±7.51 15.39±12.56 3) 5) 15.39±11.74 3) 5)

13.57±10.95 3) 5) 14.66±13.36 3) 5) 14.97±16.21 3) 5)

26.94±13.13 28.35±15.06 34.95±20.48

27.34±15.50 27.86±16.43 26.63±18.02

22.47±15.41 23.73±18.07 26.18±22.60

23.29±18.81 23.79±18.45 24.18±17.85 1)

   Notes: compared with that before treatment in the same group, 1) P<0.05, 2) P<0.01, 3) P<0.001; compared with that in the sham-moxibustion group at the same time, 4) P<0.01,5) P<0.05.

6 weeks after the treatment, 4 times altogether. (2) Of the three acupoints selected in the treatment, the temperance change of the most painful points in the knee joint was recorded with UT325 Digital Thermo Detector Apparatus (Shanghai UniTrend Group Limited). (3) The shortest walking time of 50 yards (46 m): the patients’ shortest walking time of 46 m before and after the treatment was recorded respectively by second, and then make a comparison. The speed improvement rate = [(walking time before the treatment – walking time after the treatment) ÷ walking time before the treatment] × 100%

Statistical analysis SPSS 16.0 software was adopted for the management of data. Metrological data were expressed with mean ± standard deviation (x±s). The repeated measure of ANOVA was used for the comparison of the scores of WOMAC between two groups before and after the treatment. The independent sample t-test was used for the comparison of the temperature change and the shortest walking time of 46 m before and after the treatment. P<0.05 was considered as statistically significant difference.

RESULTS Comparison of WOMAC score before and after treatment between the two groups It was shown in Table 2 that there was no significant difference in the WOMAC score of two groups before the treatment (P>0.05), showing their comparability. Compared before the treatment, the WOMAC scores in the moxibustion group of week 3, week 6 of the treatment and follow-up visit were obviously decreased (P＜0.05, P＜0.01, P＜0.001), while compared before the treatment, only the

stiffness score of the follow-up visit in the shammoxibustion group was lowered. Compared with the sham-moxibustion group, the pain, stiffness and physical function score of week 6 of the treatment and follow-up visit in the moxibustion group had a more obviously decrease.

Comparison of local skin temperature during the treatment between the two groups Because the thermometer was applied after the beginning of the trial, only part of the patients’ skin temperature change during the moxibustion was recorded. It was shown in the Table 3 that the local skin temperature in two groups were both significantly improved after the treatment (P<0.01, P<0.001), and the significant between- group difference of the skin temperature after the treatment could be found (P<0.001), which indicated that the warming effect in the moxibustion group was more obvious than that in the sham-moxibustion group. Table 3  Comparison of local skin temperature during the treatment of knee osteoarthritis patients between the two groups Groups

Patients Before treatment

After treatment

Moxibustion

24

29.11±1.16

49.81±3.101)3)

Sham-moxibustion

22

28.52±1.34

40.98±1.67 2)

t value

1.614

11.876

P value

>0.05

<0.001

  

   Notes: compared with that before treatment in the same group, 1)  P<0.001, 2) P<0.01; compared with that after treatment in the shammoxibustion group, 3) P<0.001.

Comparison of the shortest walking time of 46 m before and after treatment between the two groups From the Table 4, there was no significant difference of shortest walking time before the treatment between the two groups (P>0.05), showing their comparability. After the treatment, the shortest walking time in the moxibustion group was obviously shorten (t=3.444, P<0.01), while no difference was found in the sham-moxibustion group before and after

World Journal ofAcupuncture-Moxibustion (WJAM)

Vol. 22, No.2, 30th Jun. 2012

·32· Table4 Comparisonof theshortest walkingtime of 46m ofknee osteoarthritispatientsbefore andafter treatment betweenthe twogroups Fasting walking time of 46 m (s)

Speed improvement Before treatment After treatment rate (%)

Groups

Patients

Moxibustion

31

34.73±5.65

32.10±4.87 1)

6.68±13.28

Shammoxibustion

28

33.69±6.11

32.31±5.44

2.75±14.82

tvalue

0.680

0.157

1.074

Pvalue

>0.05

>0.05

>0.05

Notes: compared with that before the treatment, 1) P<0.01.

the treatment, also there was no statistically significant difference between the two groups.

DISCUSSION Knee osteoarthritis is very common among elderly people with a significant impact on patients' quality of life because of the pain and functional disorder[9-IOj, disability rate of which could up to 53%[II]. At present there is no effective therapy to cure KOA, which could only relieve symptoms. Nowadays Nonsteroidal Antiinflammatory Drug (NSAID) is often prescribed in the clinical practice'l", which has serious adverse effect and not for long-time use, especially the influence on the gastrointestinal tract may make patients drop the treatment [13-14]. As a green pure nature therapy, the acupuncture makes less adverse effect in the gastrointestinal tract and has a better clinical effect, so it is very popular among patients. There are plenty of clinical trials on the treatment of KOA with traditional moxibustion, however, most results of these trials are positive and the quality of research design is low, such as inappropriate randomized methods, unreasonable and even no design of controlled group, inappropriate or no blinding method, inappropriate hiding method for assessor or other stuff, undefined inclusive criteria, nonstandard diagnostic criteria or confused effect observation indices, which couldn't have a comparison with other clinical trials of KOA. With the exactly randomized controlled design standard and novel sham moxibustion device invented by Professor ZHAO Bai-xiao, the results of this trial shows that the WOMAC scores of week 3, week 6 of the treatment and follow-up visit in the moxibustion group are obviously decreased. Although compared before the treatment, only the stiffness score of the follow-up visit in the sham-moxibustion group was significantly different, the scores of pain and physical disfunction are both decreased as time went on; there is no significant difference between the two groups at week 3 of the treatment, but the significant difference could be found at week 6 of the treatment, which

ELSEVIER

indicates that the effect of moxibustion is improved with time went by, and the fact that the significant difference between the two groups still could be found during follow-up visit meant that medical effect continued until 6 weeks after the treatment. The problem that for how long can this treatment last would be further analyzed. During the treatment, the skin temperature of acupoints in the two groups were both increased, which was more obvious in the moxibustion group. The device applied in the sham-moxibustion group that was invented to place insulation metal membrane in the bottom to insolate the moxa-produced heat and smoke and prevent them from radiating to the skin wasn't able to insolate the heat completely and some heat pass on the skin to have some medical effect. Although compared before the treatment, only stiffness score of the follow-up visit in the shammoxibustion group was lowered, the score of pain and physical function generally had a declining curve. The method that was used in this research to make patients and therapy operator double-blinding was as follows: CD exclude the patients with history of moxibustion; ® the appearance, burning process and residue of sham moxa was the same as real moxa, but the insulation metal membrane in the bottom base could insolates the moxa-produced heat and smoke; ® the patients in the two groups were treated separately, which stopped the communication among patients; @ the therapy operators were all postgraduate student without acupuncture major from our university. The treatment was given respectively, meaning no cross between patients and operators, no idea of the situation in the other group. The therapists was forbid to ask for the patients' feelings, and no hint of words about treatment feelings could be given; @ the device couldn't completely insolates the moxaproduced heat, so the patients still may feel warm, which help the carry-out of blinding method instead, because real and sham moxa couldn't be identified by patients and operators. The clinical effect of moxibustion still can be seen on the shortest walking time of 46 m. Although no significant difference between groups after the treatment, the time was obviously shorten in the moxibustion group. Besides, there were 10 people who once had blister during the treatment, which had soybean size and disappeared in 3 days without any special instructions, and none of them had infection. Due to the small size of the sample, the problem that whether the patients with blister had better effect than

ELSEVIER

World Journal ofAcupuncture-Moxibustion (WJAM) Vol. 22, No.2, 30th Jun. 2012

·33 •

those without blister has not been analyzed, which need to have a big-sample statistical analysis in the further. This research has attempted to have a randomized, double-blinded and controlled clinical trial on the treatment of KOA with moxibustion. There are some deficiency needs to be improved in the future, but we have initially confirmed that the treatment of moxibustion for KOA is safe, effective, easy to operate, and has no adverse reaction, which is suitable among people. In the further, we will improve the design of real-sham moxa pillar, expand the size of sample and have a further discuss on the mechanism.

[7]

[8]

[9]

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Yang ZM. Sciences of Acupuncture and Moxibustion Technique (Chin). Shanghai: Shanghai Scientific and Technical Publishing House; 2004:37. Sangdee C, Teekachunhatean S, Sananpanich K, Sugandhavesa N, Chiewchantanakit S, Pojchamarnwiputh S, et al. E1ectroacupuncture versus diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. BMC Complement Altern Med 2002(2):3. Tukmachi E, Jubb R, Dempsey E, Jones P. The effect of acupuncture on the symptoms of knee osteoarthritis: an open randomized controlled study. Acupunct Med 2004; 22(1):14-22. Su JT, Zhou QH, Li R, Zhang J, Li WH, Wang Q. The transient antalgic effect of wrist-ankle acupuncture for the treatment of acute lumbago: a randomized controlled trial. Chin Acup-Mox (Chin) 2010;30(8):617-622. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 2004; 141(12):901-910. Wen L. Could clinical study on acupuncture in China yet

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put forward evidence? - The visit of Chen ken, a senior medical officer in the Western Pacific Region of WHO to Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences. Chin Acup-Mox (Chin) 2001;21(7):388. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee. Arthritis Rheum 2000;43(9):1905-1915. Zhao B, Wang X, Lin Z, Liu R, Lao L. A novel sham moxibustion device: a randomized, placebo controlled trial. Compl Ther Med (Chin)2006; 14(1):53-60. Dawson J, Linsell L, Zondervan K, Rose P, Carr A, Randall T, et al. Impact of persistent hip or knee pain on overall health status in elderly people: a longitudinal population study. Arthritis Rheum 2005;53(3):368-374. Palmer KT, Reading I, Calnan M, Linaker C, Coggon D. Does knee pain in the community behave like a regional pain syndrome? Prospective cohort study of incidence and persistence. Ann Rheum Dis 2007; 66(9):1190-1194. The Chinese Orthopaedic Association. Diagnosis and treatment guide of osteoarthritis (2007 Edition). Chin J Orthop (Chin) 2007;27(10):793-796. Watson M, Brookes ST, Faulkner A, Kirwan J. WITHDRAWN: Non-aspirin, non-steroidal antiinflammatory drugs for treating osteoarthritis of the knee. Cochrane Database Syst Rev 2007;18(1):CD 000142. Tramer MR, Moore RA, Reynolds DJ, Mcquay HJ. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain 2000;85(1-2): 169-182. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A. Gastroin testinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long term Arthritis Safety Study. JAMA 2000; 284(10): 1247-1255. (Editor: YANG Li-li

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