Study design
This is a multi-center, blinded RCT with two parallel groups: the Tuina manipulation group and Health care education group. The research protocol has been approved by the Regional Ethics Review Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine(Project No.2019-097).It has been registered with the China Clinical Trial Registry-------ChiCTR-2000030154. A total of 170 eligible patients with knee osteoarthritis will be randomly assigned to these groups in a 1:1 ratio. All patients will be provided with written informed consent. Outcome assessments and statistical analyses will be performed by independent investigators blinded to patient assignments. The research design is illustrated in the flow chart of Figure 1, and the research schedule is shown in Figure 2.
Participants
Eligible participants are patients diagnosed with KOA who notified of the trial if knee pain or dysfunction affects their daily activities at work or elsewhere.If patients express willingness, the clinical trial communicator will describe the trial to them and ask them if they would like to participate.If the patient wishes, the interviewee will conduct a face-to-face interview in the reception room of the hospital.Patients who meet the inclusion criteria but do not meet the exclusion criteria can join after signing the consent form.
recruitment
We made this trial public to potential participants in the following ways: 1) posting recruitment posters in the hospital's outpatient and ward corridors; 2) making roll-ups in community centers near the hospital; 3) the hospital's official Weibo post recruitment information; And the hospital's official WeChat platform, and 4) print ads in newspapers.
Inclusion criteria
Participants who meet all of the following criteria can be enrolled:
1) Meet the diagnostic criteria for knee osteoarthritis
2) Knee X-ray Kellgren and Lawrence grade 1 is graded: the joint space is suspected to be narrow and may have osteophytes
3) The intensity of pain measured on visual analogue scale (VAS) at the time of recruitment exceeds 3 points
4) Age between 40 and 65 years old,male or female
5) Did not receive any massage or other related treatment within the last 4 weeks of the study
6) Those who voluntarily join the trial and sign the informed consent form
7) Ability and willingness to comply with interventions and follow-up assessments
8) Agree to not receive other related treatments (including cartilage softeners) during treatment
Exclusion criteria
Participants who meet any of the following conditions will be excluded:
1) Those with a history of trauma and surgery in the knee; patients with diseases such as tumors, tuberculosis, and osteomyelitis in the knee
2) severe liver and kidney dysfunction, severe cardiovascular disease, diabetes and mental illness affect the massage therapy
3) unable to communicate or provide self-care due to mental or psychological disorders associated with severe neurosis or dementia
4) Those with physical pain caused by other diseases
5) Partial damage in acute phase or local skin damage
6) The duration of knee-joint pain or stiffness episode is less than 0.5 hours
7) Pain attack occurs less than 3 months or more than 2 years
8) Failure to adhere to treatment at the prescribed time
9) Use massage or other related treatments within one week before entering the study
10) Participate in other clinical trials
11) Use any other treatment (drug or non-drug) in the middle
Dropout criteria
Participants who have not completed the clinical program for the following reasons should be considered as exited
1) Patient withdrawal (poor efficacy or adverse reactions)
2) Loss of follow-up
3) The researcher removes the patient (poor compliance, complications or serious adverse events)
The test communicator will have in-depth communication with the patient who wants to withdraw from the trial because of low effectiveness or lack of time to promote retention.
Randomization
In this trial, Yueyang Hospital Science and Technology Department will generate a random sequence using a random number generator (SPSS 21.0, SPSS Inc., Chicago, IL, USA). Random numbers will be placed in opaque envelopes, numbered sequentially, and sent to therapists. Envelopes are opened in numerical order to determine the assignment of participants through the screening test. After completing the baseline questionnaire, the therapist exposes the post-physical examination and after the exclusion criteria, so that the study administrator, therapist, and the study participant are unaware of the group assignment until all baseline data has been collected.
Blinding
As an opening clinical trial, both of clinicians and patients know that they will receive which treatment and need to work with their physician or therapist before treatment. The clinical efficacy assessment will be conducted by the clinical assessor on the phone, and the assessor will conceal the treatment task. During the data collection and analysis phase, clinical researchers, evaluators, and statisticians do not share research information with each other.
Interventions
Participants will receive 8 treatments within 4 weeks.The treatment will be carried out by a senior therapist who has studied acupuncture and massage and has been licensed for more than 10 years.Participants will be asked to rest for 15 minutes before treatment.A constant room temperature of 23 to 25°C will be maintained to ensure that the patient is comfortable and relaxed during treatment.The intervention will be done twice a week. Each treatment will last for 20 minutes.Knee function will be assessed at baseline and 2, 4, 8, 12 weeks after baseline assessment.
Tuina manipulation group
In this part of the study, the therapist will use a two-step approach to relieve pain around the knee and improve knee dysfunction by releasing soft tissue around the knee by inducing general relaxation while addressing specific structural problems. It is determined by the clinician that it may be helpful to the patient's KOA, or by promoting air transport (activation of blood circulation according to TCM theory). The specific scheme used is as follows.
The specific implementation method of massage, that is, based on the conventional acupoint massage around the knee joint of the patient, the pain point is searched by the patient description and the palpation of the surgeon, and the pain point is treated with sputum, 20 minutes each time, 3 times a week, and the course of treatment is 4 weeks.
Step one: Check pain point around the knee joint
The patient is supine, the examiner holds the upper part of the patient's knee joint in one hand, and the thumb of the other hand is in the inner knee, the outer knee eyes, the adductor nodules, the medial and lateral joint space, the femur and tibia, the periorbital and the axillary fossa. Sliding and pressing to find pain points of these places.
When checking the popliteal fossa, take the prone position and bend the knee, and then slide and press the center of the popliteal, the lower part of the popliteal,the outside and in the upper of the popliteal. When inspecting the inner side of the apex patellae, the examiner needs to push the patella downwards by left hand, so that the apex patellae is lifted up, with the thumb of your right hand facing upward and press facies medialis of the apex patellae with examiner’s fingertips .
Step two:tuina local manipulation
The patient is placed in the supine position.The doctor stands on the affected side, tuina manipulate on a regular acupuncture point around the patient's knee joint,and then use press and rub manipulation operate on the patient's pain point. The pain point is generally considered as reflecting the underlying condition and is often used for pain relief.Press and rub manipulation frequency reach 120-140 times / min.Then patient is placed in the prone position, doctor repeat the above operation.
Health Care Education Group
The specific implementation method of health care education, the patients with knee osteoarthritis to be included, participate in a 45-minute health care education lecture three times a week for 4 weeks. The program includes a 30-minute lecture and a 15-minute discussion. The content includes diagnosis of knee osteoarthritis, healthy diet,pain management, physical and mental health, correct lifestyle.
Allowance of concurrent treatment of patients
All KOA treatments are prohibited during the trial, including oral muscle relaxants, anesthetics, analgesics, surgery, drug injections, acupuncture and physical therapy. They may receive any treatment that is not related to knee pain. Any changes to concurrent treatment are recorded for each visit.
Primary outcome measurements
KOOS
KOOS has been widely used in research and has been shown to have the efficiency and reliability of neck pain measurements [22]. We used a knee injury and osteoarthritis outcome score (KOOS) pain test (0-100 scale, 0 for extreme knee problems, 100 for knee-free problems) as our primary at baseline and at the end of the intervention. Clinical results. The KOOS scale is an extension of WOMAC, a self-administered 42 questionnaire covering five patient-related dimensions: pain, other disease-specific symptoms, daily functional activities, motor and recreational functions, and knee-related Quality of Life. The scale is an effective, reliable, and responsive method for measuring results with good test reliability and structural validity for total joint replacement. We used other KOOS subscale scores as the primary outcome.
Secondary outcome measurements
MPQ
The MPQ(McGill Pain questionnaire) is a very common scale that measures and evaluates various pains [23-24]. The MPQ contains 4 types of 20 pain descriptions. Each group of words is arranged in increasing order. One to ten groups are sensory, 11 to 15 are affective, and 16 are Evaluation, 17 to 20 groups are other related classes (miscellaneous). The test subject selects a word with the same degree of pain in each group of words (no suitable one can not be selected)
SF-36
The SF-36 questionnaire assessed the association between health-related quality of life and various factors [25]. It is widely used in the field of quality of life measurement, clinical trial evaluation and health policy assessment. It consists of 36 questions, divided into Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP): General Health (GH), Vitality, social function (SF), Role Emotional, (RE) and mental health (MH) General Health(GH)and other eight aspects. For each domain, the score ranges from 0 to 100, with higher scores reflecting a better quality of life. The SF-36 will be evaluated using repeated longitudinal analysis.
Safety evaluation
Treatment safety will be assessed by researchers monitoring patient symptoms before and after treatment. In this trial, adverse events (AEs), the following events will be defined as adverse events: (1) severe pain; (2) syncope; (3) deterioration in walking function; (4) caused hospitalization; (5) life Changes in threats,all will be carefully recorded in the case report form.For any AEs, whether or not it is related to this treatment course, treatment should be stopped immediately. The patient should be treated and the AEs will be reported to the responsible unit and the ethics committee to determine if the patient should withdraw from treatment.
Follow-up
To assess short-term efficacy, long-term efficacy, and safety of interventions, we will track participants for 2 months after the trial. Within 2 months of unsupervised follow-up, no participants will receive special treatment other than regular knee care. At Weeks 8 and 12, the results evaluators will investigate the recurrence of their neck pain by telephone participants. Patients can also inform the assessor of their clinical signs and mood changes by email, text message or WeChat at the relevant time.During the follow-up period after the trial, any uncomfortable health issues will be assessed and the committee will be notified for a decision.
Data collecting and monitoring
Results The assessor will record the clinical results in the Case Report Form (CRF), the treatment effect assessment of the intervention, and the physiological function and details of the adverse events. The completed CRF is reviewed by a four-person steering committee composed of the heads of the four research centers and submitted to the data stewards who are independent of the research team, do not know the grouping, use data entry and manage an Excel database. All data administrators have data analysis qualifications and unified training. To ensure the accuracy of the data, the two data administrators independently enter the information and perform proofreading. If there is a problem with the information in the CRF, the data administrator can fill out the lookup table and then the data administrator can modify the data according to any revisions of the Steering Committee. After confirming that the database is correct, the steering committee, data stewards, and statisticians will lock the database.
Health economics
All costs associated with this test will be recorded. These costs mainly include medical costs for direct treatment of KOA, such as inpatient bed fees, outpatient registration fees, Tuina treatment fees, daily care and testing fees, and in addition, the cost of treatment for any adverse event will be recorded and included in health costs evaluation.
Sample size calculation
The rate of the expectation of the effectiveness in Tuina manipulation group is 70% and the efficacy rate for health education is 45% based on the literature. The sample size was calculated with a significance level of 0.05 and power of 0.90, which also considering a maximum dropout tolerance of 10%. At last, 170 patients are needed for the trial, with 85 for each group in the trail center.
Data analysis
Demographic and baseline data will be analyzed with standard, descriptive statistics. Between-group differences will be tested using repeated measures analysis of variance.The acceptable significance level for all analyses was P <0.05. We will perform the entire data analysis process by statisticians who are independent of the research team and have no knowledge of the group settings.Data analysis was performed using SPSS software (for Microsoft Windows® SPSS, Inc., SPSS 21.0 KO, Chicago, Illinois, USA).
quality control
In order to improve the reliability of the results of this study, we designed quality control procedures from the following aspects: (1) Baseline homogeneity: This study limits the age of participants to between 40 and 65, and we will assess people with similar living habits; (2) Tuina manipulation: In this study, all researchers will be trained to fully understand the design and process of the trial, the use of CRF, and the control of the manipulation. To avoid operational differences, two experienced doctors received specialized standardized training before the trial and performed all treatments in accordance with standard operating procedures. In addition, during the process of treatment, except for seeking pain points, unnecessary communication between the therapist and the patient is prohibited; (3) Pain point: considering the importance of pain point seeking for accurate treatment evaluation, the pain threshold at the tenderness point will be measured after each treatment to evaluate whether there is a significant difference in stimulus and pain perception before and after each treatment, which will help to rule out the bias of pain point.