This study is a randomized, double-blind, sham-controlled clinical trial experiment. The whole process of this research was carried out in the Treatment Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. Eligible volunteers will be randomly assigned into the experimental group and the control group. The treatment cycle lasts for 4 weeks, with 3 treatments per week. Visits are made in the 4th, 8th, and 12th weeks after the treatment, and the results are recorded. (Fig. 1)
The 60 volunteers needed for this research will be recruited by, but not limited to, the review and screening of the Dermatology Clinic of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, social media recruitment advertisements, community promotion, recruitment flyers, and online recruitment. Meanwhile, two research assistants will go to the Dermatology Clinic of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine to recruit patients every week. The research assistant will inform patients and their guardians of the details of the study, the benefits, and the potential risks before the start of the study in detail. The recruited patients will get a paper informed consent and sign the informed consent under the witness of the research assistant. If the patient does not recognize words, his guardian will sign on his behalf or reach an informed verbal consent (record audio or video).
- Those who meet the diagnostic criteria of chronic spontaneous urticaria in EAACI/GA2LEN/EDF/WAO urticaria diagnostic guidelines (2017) and China urticaria diagnostic guidelines (2014);
- Aged between 18 and 70 years;
- Sign the informed consent form and participate in this study voluntarily.
Note: patients who meet the above three criteria at the same time can be included in this study.
- Patients who are unconscious , unable to express subjective discomfort symptoms, and mentally ill patients;
- Patients with progressive malignant tumor or other serious wasting diseases, and those prone to co-infection and bleeding;
- Patients with cardiovascular, liver, kidney, digestive, hematopoietic and other serious primary diseases;
- Pregnant and lactating women.
- Patients who have taken antihistamines within 2 weeks, and steroids and immunosuppressive drugs within 1 month before the study;
- Patients who are currently participating in other ongoing clinical studies.
Note: All patients who meet any of the above items will be excluded.
Treatment discontinuation criteria
- Clinical cure,
- The participants has severe complications or worsening of the condition that cannot continue the treatment during the study;
- The participants who require to withdraw from the clinical study halfway.
- Clinically cured patients;
- A total of 3 follow-up visits were carried out at the 4th, 8th, and 12th week respectively.
- Lost to follow-up for 1 month, fill in the lost follow-up record and terminate the follow-up.
Randomization and allocation concealment
After the baseline assessment of volunteers, 60 participants were randomly divided into two groups: acupuncture group and micro-acupuncture group. According to 1:1 distribution, there were 30 participants in each group. The randomization method adopted was the central randomization. Randomized data and results were managed by an independent research assistant who knew nothing about other parts of this research. The research assistant would contact qualified patients to enter the corresponding group for the research.
This study is a double-blind trial. Due to the nature of acupuncture treatment, the acupuncturists who deliver the treatment to the participants will not be blind to the treatment allocation. All acupuncture therapists will not participate in the process of grouping patients and the final evaluation process. In addition, all volunteers, effect assessors, and statisticians will be unaware of the grouping results. We will evaluate the blinding effect end of study.
The acupuncture group was treated by an acupuncture therapist using sterile needles (Huatuo disposable acupuncture needle, Suzhou Medical Supplies Factory Co. Ltd.) in sizes of 0.25 × 25 mm or 0.25 × 40 mm. Table 1 and Figure 2 are the location of acupuncture points. During the treatment, the acupuncture therapist will pierce the needle into the corresponding acupuncture point, insert the needle to a safe depth, and perform uniform replenishing and reducing techniques(Lift, insert, twist, turn) until each point achieves the Deqi sensation. Needles will be retained for 30 minutes per session, and stimulation of the needles is manipulated every ten minutes.
Volunteers in the micro-acupuncture group would receive 12 micro-acupuncture treatments in 4 weeks. The same acupuncture therapist would use the same specifications of acupuncture needles for non-acupoint acupuncture. The number of acupunctures was the same, and the depth of acupuncture was 2-3mm. Needles were retained for 30 minutes. During this period, no manipulation was performed to avoid excessive stimulation and prevent the participants achieving the Deqi sensation.
Urticaria activity score (UAS) and Visual Analogue Scale (VAS) were evaluated after 1 week in the baseline period and 4 weeks in the treatment period. Dermatology Life Quality Index (DLQI) was evaluated after 1 week of the baseline period and the 4th week of the treatment period. During the follow-up, the patients filled in UAS, VAS and DLQI for the corresponding follow-up week. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Pittsburgh Sleep Quality Index (PSQI) were evaluated at the entry and the exit point. Adverse events would be summarized at 1st, 2nd, 3rd, and 4th week after randomization. (Table 2)
Gender, age, education level, occupation, marital status, etc. Recorded at the time of enrollment.
- Vital signs: heart rate (heart Rhythm), respiratory rate, blood pressure. Recorded at each assessment.
- Basic medical history collection, routine physical examination. Recorded at the time of enrollment.
Primary outcome measurement
Urticaria activity score (UAS)(21, 22). Evaluate once a day for 7 consecutive days, and calculate the total score within 7 days.
Secondary outcome measurements
Pruritus score: The degree of itching was evaluated by the Visual Analogue Scale (VAS)(23, 24), which was evaluated once a day for 7 consecutive days. The total score within 7 days was calculated.
Quality of life score: The Dermatology Life Quality Index (DLQI)(25-27) was used to evaluate the quality of life of patients
Psychological assessment: The Hamilton Depression Scale (HAMD)(28) and Hamilton Anxiety Scale (HAMA) (29)were used for evaluation.
Sleep assessment: Pittsburgh Sleep Quality Index (PSQI)(30) was used for evaluation.
Adverse events and treatment
During the study intervention, any adverse events related to acupuncture would be recorded. Possible adverse events were local hematoma, acupuncture syncope, sticking of the needle, bent needles and broken needles,etc. Timely treatment measures should be taken according to the patient's condition when an adverse reaction occurred. Emergency medical assistance would be sought if any serious adverse effect occurred. Whether the adverse events were related to the treatment in this trial, they would be recorded in detail, including the date of occurrence, time, symptom, degree, duration, laboratory inspection indicators, processing methods and results. Serious adverse events would be immediately reported to the primary investigator to assess whether to proceed with the study.
To ensure the successful and smooth study implementation, all researchers would be uniformly required to receive standardized training before the research starts. The collected clinical data would be recorded and managed by two researchers who have received rigorous training on using paper and electronic case report forms (CRFs). In order to avoid data entry errors, data would be proofread by two independent researchers when entering the electronic CRFs, and they would proofread each other before finalizing. Data would be uploaded to www.amreg.org and managed by the person in charge.
This study aims to assess the efficacy of acupuncture on the treatment of chronic urticaria and the feasibility of widespread promotion. We did not perform a sample size calculation for this study, but used a convenience sample based on the known availability of study participants in the research base. At the same time, considering that too many volunteers could not be recruited and the dropout rate of 20%, we estimated that we could recruit 60 people for this study(31). There would be 30 people in the acupuncture group and the micro-acupuncture group. The outcomes of this study would facilitate the calculation of the appropriate sample size for other randomized controlled trials in the future.
- Case distribution: Different data set sizes for each group, detailed list of dropped cases, aborted cases and reasons.
- Comparability analysis: Compare demographic data and other basic value indicators to measure the comparability of the two groups.
- Compliance analysis: Compare whether the patients in each group are implemented according to the design plan. To make sure they do not take the drugs and foods prohibited in the plan. Compliance is evaluated based on the records of the Case Report Form (CRF), and calculates the number and percentage of cases <80%, 80%~100%, >100%.
- Effectiveness analysis: Categorical data are described by mean of treatment difference from baseline, standard deviation, median, P25, P75, maximum and minimum. Main indicators and global indicators were analyzed by PP and ITT.
- Analysis of influencing factors: If there are significant differences in age, gender, disease type, condition, etc. before the test, or there are related factors that significantly affect the efficacy, these factors should be considered as covariates when comparing groups. Covariance analysis or logistic regression analysis is required . Meanwhile, a detailed list of combined medications is required.
- Safety evaluation: First, according to the requirements of the relevance of adverse reactions, the adverse events and adverse reactions of each group(including the number and incidence of various adverse events) should be listed first,and then the reasons and explanations.
- Data from this clinical trial will be calculated and analyzed using SAS 9.1.3/SPSS 19.0 statistical analysis software. P<0.05 will be considered that the difference is statistically significant.