This study will be conducted at the Chinese Medicine Clinical Trial Laboratory in Royal Melbourne Institute of Technology (RMIT) University, Bundoora West and City campuses. It has been designed as a randomized, single blind, non-specific controlled, and two-arm paralleled clinical trial according to the Guideline of National Statement on Ethical Conduct in Human Research 2007 (Updated May 2018) . The trial will consist of a 2-week run-in period, a 4-week intervention period and an 8-week follow-up period. This study protocol was developed as required by the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) (Additional file 1)  and the Revised STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA): extending the CONSORT Statement .
The ethics approval has been obtained from RMIT Human Research Ethics Committee (HREC) (project number: 20742). The trial has been registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12617001106325) (Additional file 2).
The participants will be based at the general population in Melbourne, Australia and recruited through advertisements on internet, posters, notice boards, leaflets, media release, social media, local newspapers, and newsletters. Participation in this research project is voluntary. The participants will be selected according to the inclusion and exclusion criteria listed in Table 1 below.
The sample size was calculated using the program G*Power 3.1.9 . Calculation of the sample size of this study was estimated on the relief of severity of the total nasal symptom score in the previously published acupuncture study . The effect size estimate is 0.6505. To achieve 80% power at the significance level 0.05 we need 45 subjects per group taking into consideration of a 10% dropout rate.
People who are interested in taking part in this trial will be provided with Participant Information Sheet with Consent Form (PIS-CF) and asked to complete a general questionnaire and screening questionnaire if they agree with PIS-CF. Written consent will be obtained from each participant before an initial interview. The activities in the initial interview will include allergen skin prick test, physical examination and Chinese medicine differential diagnosis  to achieve AR diagnosis. The participants meeting the inclusion criteria will enter the 2-week run-in period. During this period, every participant will be asked to conduct two sets of weekly baseline assessment including a 7-point scale symptom severity assessment form , a Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities (RQLQs)  and a medication usage form. All baseline assessment forms will be submitted in the first intervention session. The Figure 1 outlines the procedures of the clinical trial.
Randomization and blinding
To minimize bias, eligible participants will be randomized into either the specific-acupressure treatment group or non-specific acupressure control group. Randomization will be conducted after baseline assessment using a computer program run by an independent researcher who is not directly involved in the trial. The randomization codes will be put into individually sealed opaque envelopes with sequel trial numbers. The sealed opaque envelopes contain the information on the location of specific or non-specific acupressure points for self-administered acupressure. Each participant will be asked to pick one sealed envelope from the pack of all the envelopes and pass it onto the registered acupuncturist. This acupuncturist is the only person who knows the participants’ group allocation in the trial. Neither the participants nor other investigators (such as data entry personnel and data analyst) will know the participants’ allocation to receive specific or non-specific acupressure treatment. The randomization codes and the allocation of the participants will be revealed once the RCT is completed. However, in the event of the need of this grouping information (e.g., a participant experiencing severe adverse events), the investigators will access the grouping data on the request of the medical doctor. The relevant information will be documented in the participant’s case report form.
After randomization, the registered acupuncturist will provide detailed instructions and training on self-administered acupressure techniques to each participant individually. A pictorial instruction showing the location of acupressure points will be provided to the participants for further reference. Participants will be asked to perform self-administered acupressure on either five specific or non-specific acupressure points following the sequence from point 1 to point 5, for at least one minute each point, twice a day for four weeks and complete the self-assessment on a weekly basis. During the treatment period, participants are required to have a weekly visit to the Clinical Trial Laboratory and the registered acupuncturist will monitor their skills to ensure the accurate performance of self-administered acupressure techniques. Messages will be sent to each participant to remind them to continue performing acupressure and attend the Clinical Trial Laboratory during each week. The Figure 2 below illustrates the location of five specific acupressure points and five non-specific acupressure points.
Specific self-administered acupressure
Participants in specific acupressure group will apply self-administered acupressure on five specific acupressure points including LI4 Hegu, GV23 Shangxing, BL2 Zanzhu, LI20 Yingxiang and GB20 Fengchi. The acupressure points were selected based on the review of classical and modern literature [11, 16, 22, 25].
Non-specific self-administered acupressure
Participants in non-specific acupressure group will apply self-administered acupressure on another five non-specific acupressure points which are true acupuncture points on the body but not specifically indicated for AR treatment according to literature including Extra Luozhen, GV20 Baihui, GB4 Hanyan, SI18 Quanliao and GB12 Wangu [11, 25].
Symptomatic relief medications
Participants will be allowed to continue their existing management for AR, such as pharmacological therapy. They will be asked to record the details of all medications used in the medication usage form.
Primary and secondary outcome measures will be included in this clinical trial. The comparison between two groups will be at baseline, at the end of the treatment period and at the end of the follow-up period. The RCT schedule of recruitment, interventions and assessments is shown in Figure 3.
Primary outcome measures
The primary outcome measure will be AR symptomatic relief measured by 7-point scale symptom severity with the score ranging from 1 to 7. It contains four domains including I (nasal symptom severity), II (non-nasal symptom severity) and IV (Quality-of-life assessment of rhinitis severity) where a higher score indicates severer symptoms and better quality of life (QoL) as well as III (Global assessment of nasal and non-nasal symptom severity) where a lower score indicates severer symptoms . The primary outcome measure will be assessed in baseline and intervention period on a weekly basis and in follow-up period on a fortnightly basis.
Secondary outcome measures
The secondary outcome measures will consist of RQLQs , relief medication scores, adverse events and participants’ opinion about this clinical trial. RQLQs is used to assess the patient’s quality of life and daily activities which contain seven domains with scores from 0 to 6; a higher score indicates a severer impact on QoL . The use of anti-allergic medication is calculated as each daily dose of antihistamines or decongestants nasal spray or eye drop was equivalent to 1 point; oral antihistamines as 2 points and steroid nasal spray or eye drop as 3 points . If the participants use oral corticosteroids or acupuncture for AR during the trial period, they will be asked to discontinue the treatment and considered as withdrawal from this study. Adverse events will be self-monitored and recorded in the adverse events form. If there are severe adverse events from the self-administered acupressure, the relevant participants will be asked to terminate the study and contact the researchers immediately. They will be referred to general practitioners or the emergency department for management. All adverse events will be under investigations and reported in writing to the RMIT HREC immediately. A questionnaire will be used to seek participants’ opinion on the expectancy of self-administered acupressure for AR and the credibility of the blinding method used in the study.
RQLQs and relief medication scores will be assessed at baseline, intervention period (weekly) and follow-up period (fortnightly). Acupressure dosage and adverse events will be recorded in a weekly form during the treatment period to monitor participants’ compliance and safety, and adverse events will be further assessed fortnightly in follow-up period. Participants’ opinion will be assessed at the end of first and final week of intervention period.
An individual file for each participant will be used to archive the hard copy of case record forms including informed consent, results of allergen skin prick test, results of physical examinations and all completed questionnaires. The files will be stored in the lock-up cabinet. The electronic submission documents will be kept in a RMIT University password-protected computer. Only the investigators of this study will have the authority to access the data. The results of the study and the grouping information of the participants will be provided to the individual after completion of the trial. Publications will only report aggregated data. Personal identity will not be disclosed.
Statistical analyses will be performed by an independent statistician at RMIT University using IBM SPSS Statistics for Windows Version 25 software (IBM Corp., Armonk, NY, USA). Data will be analyzed by chi-square test, t-test or ANOVA. All analyses will follow the intention-to-treat principle. The Worst-Case Scenario method will be employed to deal with the missing data. Participants enrolled in the study with data from at least one treatment will be included for analysis.
All comparisons will be two-tailed and p values < 0.05 will be considered as statistical significance. Subgroup analysis may be performed according to syndrome differential diagnosis of Chinese medicine, severity of symptoms or age group of participants.