Effects of laser moxibustion on patients with knee osteoarthritis

ISRCTN	ISRCTN15030019
DOI	https://doi.org/10.1186/ISRCTN15030019
Protocol serial number	N/A
Sponsor	Shanghai University of Traditional Chinese Medicine (China)
Funders	National Natural Science Foundation of China (81320108028), National Basic Research Program of China (2015CB554505), Key Project of State Administration of Traditional Chinese Medicine of China (ZYSNXD-CC-ZDXK-07)

Submission date: 14/03/2017
Registration date: 16/03/2017
Last edited: 08/04/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Osteoarthritis, a common joint disorder, is the most common form of arthritis in the world. The knee joint is the most common site affected by osteoarthritis. Joint pain caused by knee osteoarthritis can severely reduce the patient’s quality of life. The aim of this study is to observe the effect and safety of CO2 laser irradiation on acupuncture points (laser moxibustion) in patients with knee osteoarthritis.

Who can participate?
Patients aged 50 to 75 years undergoing conventional knee osteoarthritis treatment

What does the study involve?
Participants are randomly allocated to be treated with either real (verum) or sham laser moxibustion at the acupoints on the affected knee(s). Patients in both groups receive 20 minutes of treatment, three times per week for 4 weeks. The effects of treatment are assessed at the start of the study, week 2 (mid-term), week 4 (the end of treatment), week 8, 12 and 24.

What are the possible benefits and risks of participating?
Laser moxibustion can reduce pain and improve knee joint stiffness and function in patients with knee osteoarthritis. Some patients might have local skin flushing or blistering (not instantly, but usually one day after treatment) at the site of treatment. Usually the blister is naturally absorbed within a day or two without obvious scarring of the skin.

Where is the study run from?
1. Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine (China)
2. Renji Hospital affiliated to Shanghai Jiaotong University (south part) (China)
3. Shanghai East Hospital affiliated to Tongji University (China)
4. Shanghai Tongren Hospital affiliated to Shanghai Jiaotong University (China)
5. Shanghai Hudong Hospital (China)

When is the study starting and how long is it expected to run for?
January 2014 to December 2018

Who is funding the study?
1. National Basic Research Program of China
2. National Natural Science Foundation of China
3. Shanghai development office of Traditional Chinese Medicine

Who is the main contact?
Prof. Xueyong Shen
sxy1@shutcm.edu.cn

Contact information

Mr Xueyong Shen
Scientific

Shanghai University of Traditional Chinese Medicine (China)
1200 Cailun Road
Pudong new district
Shanghai
201203
China

Phone	+86 (0)21 51322175
Email	sxy1@shutcm.edu.cn

Dr Ke Cheng
Public

1200 Cailun Road
Pudong district
Shanghai
201203
China

Phone	+86 (0)21 51322605
Email	cheng_ker@hotmail.com

Study information

Primary study design	Interventional
Study design	Randomized multi-center double-blind placebo-controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effectiveness of CO2 laser moxibustion treatment for knee osteoarthritis: a double-blind randomized controlled trial
Study objectives	A 4-week CO2 laser moxibustion treatment regimen reduces pain among patients with knee OA as compared with sham laser moxibustion treatment, and the therapeutic effect might be related to the cytokines such as Interleukin in serum.
Ethics approval(s)	Current ethics approval as of 28/08/2018: 1. Institutional Review Board (IRB) of Shuguang hospital affiliated to Shanghai University of traditional Chinese medicine, No. 2014-341-37-01 (2014/08/13), No. 2014-341-37-02 (2015/08/13), No. 2014-341-37-03 (2016/08/31). 2. IRB of Shanghai East Hospital affiliated to Tongji University, 2014/10, No. 2013-24 3. IRB of Renji Hospital affiliated to Shanghai Jiaotong University, 2015/02/25, No. 2015-001 4. IRB of Shanghai Changning Tianshan Traditional Chinese Medicine Hospital, 2017/07/14, No. 2017TSKY04 5. IRB of Shanghai Tongren Hospital affiliated to Shanghai Jiaotong University, 2018/06/01, No. 2018-006-02 Previous ethics approval as of 24/08/2018: 1. Institutional Review Board (IRB) of Shuguang hospital affiliated to Shanghai University of traditional Chinese medicine, 13/08/2014, No. 2014-341-37-01 2. IRB of Shanghai East Hospital affiliated to Tongji University, 2014/10, No. 2013-24 3. IRB of Renji Hospital affiliated to Shanghai Jiaotong University, 2015/02/25, No. 2015-001 4. IRB of Shanghai Changning Tianshan Traditional Chinese Medicine Hospital, 2017/07/14, No. 2017TSKY04 5. IRB of Shanghai Tongren Hospital affiliated to Shanghai Jiaotong University, 2018/06/01, No. 2018-006-02 Previous ethics approval: 1. Institutional Review Board (IRB) of Shuguang hospital affiliated to Shanghai University of traditional Chinese medicine, 13/08/2014, ref: 2014-341-37-01 2. IRB of Shanghai East Hospital affiliated to Tongji University, October 2014, ref: 2013-24 3. IRB of Renji Hospital affiliated to Shanghai Jiaotong University, 25/02/2014, ref: 2015-001 4. IRB of Shanghai Tongren Hospital affiliated to Shanghai Jiaotong University, 14/03/2017, ref: 2017-32
Health condition(s) or problem(s) studied	Knee osteoarthritis
Intervention	Patients with knee osteoarthritis are randomly allocated into either verum or sham CO2 laser moxibustion groups. Patients receive verum or sham laser moxibustion treatment on Dubi (ST-35) and an Ashi (tender) point in the area of the affected knee(s). Patients in both groups receive 20 minutes of treatment, 3 times per week for 4 weeks. The effects of treatment are assessed at baseline, week 2 (mid-term), week 4 (the end of treatment), week 8, 12 and 24 after baseline.
Intervention type	Device
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	-
Primary outcome measure(s)	Knee pain, measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores from baseline to 4 weeks. The most painful joint reported by participants at baseline is assessed during the whole study. Change of WOMAC pain is also assessed at week 2, 8, 12, and 24.
Key secondary outcome measure(s)	1. Knee function, measured using the WOMAC function scores at week 4. It is also assessed at week 2, 8, 12, and 24 2. Knee stiffness, measured using the WOMAC stiffness score, and WOMAC overall score at baseline, week 2, 4, 8, 12 and 24 3. Pain, measured using the visual analog scale (VAS) at baseline, week 2, 4, 8, 12 and 24 4. Health-related quality of life, measured using the Short Form 36 (SF-36) component scales at baseline, week 4, 12 and 24 5. Walking ability, measured using the 50-feet (i.e., 15.24 meters) walking time at baseline, week 4 and 12 6. Patients’ global assessment of OA, evaluated on a five point Likert scale at week 4 7. Guess of the group assignment to assess the masking effectiveness of the trial: 7.1. Guess from the treatment providers at week 4 7.2. Guess from the participants of their allocation at week 1 after the first treatment and at week 4 8. Assessment of safety: any adverse event, whether related to treatment or not, reported by the participants and practitioners at every visit. During the 20-week follow-up period (from week 5 to week 24), each participant is telephoned every week to follow any adverse event or side effect that occurs. Serious adverse effects are reported to DSMB and Medical Ethics Committee. The participants are asked to assess the safety of the treatment after 4 weeks’ treatment, in terms of four grades: safe, relatively safe, unsafe, and very unsafe 9. Participants' sensations, asked during the treatment at every visit 10. Usage of medication, measured using a Medication Usage Log to record their daily intake of pain medications prescribed on a symptom-contingent (i.e., as per necessary, prn) basis Exploratory outcome: Serum levels of IL-1β, COX-2, COMP, TNF-α, IL-6, IL-17, IL-8, IL-4, IL-10 and IL-13 (considered as important cytokines involved in the progress of OA), measured using blood tests at baseline and week 4
Completion date	31/12/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	50 Years
Sex	All
Target sample size at registration	400
Total final enrolment	392
Key inclusion criteria	1. Diagnosed with idiopathic knee OA according to the American Rheumatism Association (ARA) classification criteria as follows: knee pain with three of the following or knee joint osteophyte with one of the following conditions: 1.1. Age over 50 years 1.2. Morning stiffness within 30 minutes of waking 1.3. Crepitus 1.4. Bony tenderness 1.5. Bony enlargement 1.6. No palpable warmth 2. Kellgren-Lawrence grade ≥ 1 (Kellgren Lawrence Grading Scale: Grade 1: doubtful narrowing of joint space and possible osteophytic lipping; Grade 2: definite osteophytes, definite narrowing of joint space, Grade 3: moderate multiple osteophytes, definite narrowing of joints space, some sclerosis and possible deformity of bone contour; Grade 4: large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone contour) 3. Moderate or greater clinically significant knee pain on most days during the past month. A minimum score of 40 of 100 on a visual analogue scale VAS at baseline is an inclusion requirement 4. Willingness to be randomly assigned, understanding and signing the informed consent
Key exclusion criteria	1. Patients are screened by blood tests (rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), etc) to rule out the possibilities of rheumatoid arthritis 2. Patients with fibromyalgia syndrome, and chronic fatigue syndrome, and ankylosing spondylitis are excluded to rule out their impact on outcome assessment 3. Use of steroid medication in the past 3 months 4. Acupuncture or moxibustion treatment received in the previous 3 months 5. Intra-articular hyaluronate injection during the past 6 months 6. Arthrocentesis or arthroscopy in the past 1 year 7. Previous history of knee/hip replacement surgery, and plan to have such surgery during the trial 8. Use of other external treatment like topical use of medication 9. Presence of serious medical conditions, including heart diseases, pulmonary diseases, kidney diseases, liver diseases or malignant tumors, systemic infection or contagious diseases and psychopathy 10. Use of trial drug in the past 30 days 11. Previous participation in other sham-controlled laser therapy 12. Recruited in other clinical trial simultaneously 13. Unable to fill measurement questionnaires
Date of first enrolment	01/12/2014
Date of final enrolment	30/06/2018

Locations

Countries of recruitment

China

Study participating centres

Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine

185 Puan Road
Luwan district
Shanghai
200021
China

Renji Hospital affiliated to Shanghai Jiaotong University (Pudong Branch)

2000 Jiangyue Road
Pudong new district
Shanghai
201112
China

Shanghai East Hospital affiliated to Tongji University

150 Gimo Road
Pudong new district
Shanghai
200120
China

Shanghai Tongren Hospital affiliated to Shanghai Jiaotong University

Shanghai
200336
China

Shanghai Hudong Hospital

95 Boxing Rd
Pudong new district
Shanghai
200129
China

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Xueyong Shen (sxy1@shutcm.edu.cn) or Dr Ke Cheng (cheng_ker@hotmail.com).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2020	28/01/2020	Yes	No
Results article		22/11/2023	08/04/2024	Yes	No
Protocol article	protocol	01/08/2020	26/11/2020	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

08/04/2024: Publication reference added.
28/01/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
28/08/2018: ethics approval updated
24/08/2018: ethics approval updated