This multicenter, single-blinded, randomized controlled trial will be conducted in the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine and the Shanghai Skin Disease Hospital in China. The trial has been registered at ClinicalTrials.gov (ID: 22Y11922200). At the time of writing this report (version 2.0, January 4, 2023), the trial has not yet begun enrollment. Participant recruitment will take place from April 15, 2023, to June 30, 2025. This protocol has been developed according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013. The checklist is presented in detail in Supplementary Table 1.

According to a previous study (32), the mean itch intensity was taken as 35.7% for the EA group, 40.4% for the sham electroacupuncture (SEA) group, and 45.9% for the sham acupuncture (SAC) group, with α = 0.05, test efficacy 1-β = 0.8, two-sided test, using the estimation of sample size formula for comparing more than two treatment groups [referring to n = 2 σ Z 1 − α / 2 τ + Z 1 − β μ A − μ B 2 , 1 − β = Φ Z − Z 1 − α / 2 τ + Φ − Z − Z 1 − α / 2 τ , Z = μ A − μ B σ 2 n , where Φ is the standard normal cumulative distribution function, μ A and μ B representing the mean of any two groups, and n is the sample size of a pair of τ comparisons (taking the maximum value)]. Consequently, the sample content was calculated to be 35 cases per group and 105 cases for the three groups. Assuming a 20% dropout rate of patients at follow-up, we calculated the sample size to be 44 cases for each group and 132 participants for the three groups (EA, SEA, and SAC). Participants will be recruited from two research centers, each targeting 66 participants.

Inclusion criteria:

To be eligible for recruitment, the patient must:

Be diagnosed with AE for a duration longer than 2 months.

Exclusion criteria:

Patients who meet any of the following criteria will be excluded:

Have been systematically treated with drugs, such as hormones or immunosuppressants, within 2 weeks.

Drop-out exclusion criteria:

Patients who meet any of the following criteria will be a dropout case; if the time is past the mid-point of participation in the overall study, the data should be included in the efficacy statistics:

Experienced unexpected events during treatment and are unfit to continue with the trial.

Exit/termination criteria:

Patients who have experienced severe adverse reactions during treatment and whose treating physician assessed that the trial is no longer appropriate.

Once eligibility is confirmed and consent is obtained, participants will be block-randomized using a non-stratified, permuted block of varying lengths (n = 2 blocks; patient distribution = 1:1:1) for each group. Independent statisticians will provide computer-generated random sequences. Distribution will be conducted using a central web-based interactive randomization service system; the patients will be assigned randomly to three groups. Participant identification numbers will be provided to make identification easier throughout the trial. The researchers who perform random grouping will need to log onto the website to view the grouping situation of each eligible participant. The authors have no access to information that could identify individual participants during or after data collection.

Because of acupuncture’s nature, blinding the physician involved in the treatment application is impossible. Each hospital will designate several operating researchers who are dermatologists trained to perform EA therapy and obtain relevant operational qualifications. Therefore, operating researchers will not participate in the statistical analysis; the treatment plan and grouping will be known only by statistical analysts. To ensure blinding, we will choose the Park Sham Device (PSD) as a placebo control in a single-blind clinical trial, use a way of not energizing the EA device, and use black eye masks to shield the participants’ eyes. The treatment device will also be the same size and material, and the treatment method will maintain a consistent frequency and intensity.

In the case of serious adverse events, the principal investigators at each participating center will decide whether allocation concealment needs to be broken. If allocation concealment is broken before the end of the trial, the data will be censored from analysis and the patients will be considered to have dropped out of the trial.

The study protocol consists of two main phases over 3 weeks: the screening and the treatment phase (Figure 1). The screening period will last 1 week; participants will be included in this phase according to the inclusion/exclusion criteria. Participants will be treated three times a week for 2 weeks, with different interventions among the groups.

Patients with AE will be enrolled in the screening phase through a dermatological outpatient service, and physical examinations and inclusion evaluations will be performed. The trial’s eligible participants will be requested to complete a written informed consent form (including the procedures, risks, and options for quitting the study). The study will be thoroughly explained to the participants by a researcher with the required training. Participant must sign an informed consent form after giving their approval. An algorithm will separate patients randomly into the EA, SEA, and SAC groups.

Patients with AE will receive interventions during the treatment phase. Patients will be checked for visual analog scale (VAS), Eczema Area and Severity Index (EASI), Dermatology Life Quality Index (DLQI), serum IgE, adverse events, and compliance during the two-week therapy period, administered three times a week. After 2 weeks, all interventions will end. We will record demographic characteristics, medical and medication histories, images of skin lesions, personal life histories, vital signs, physical examinations, and adverse effects (among other data) (Figure 2).

The PSD and Park sham needle (PSN) are purchased from AcuPrime.¹ We chose the PSD to maximize the blinding of participants because it has a double-tubed system that attaches to a plastic base and the participant’s skin (Figure 3). Double-sided tape is used to secure the device to the plastic base and the participant’s skin. Initially, in its expanded (highest) position, the inner tube is lowered to the outer tube as the needle is lowered. A real acupuncture needle or a PSN can be stored inside the PSD. The PSN is stainless steel with a length measuring 25–50 mm and looks like and is packaged similarly to an acupuncture needle. When downward pressure is applied to the handle of the PSN, the needle glides into the handle, providing the illusion that it is piercing the skin. PSD is critical to prevent the PSN from falling away from the participant’s skin and keep them from noticing whether a PSN or an actual acupuncture needle is used.

All three groups will have the PSD placed by the researchers. It will be applied to standard acupuncture points in the EA and SEA groups and sham acupuncture points in the SAC group.

Participants in the EA group will receive acupuncture with PSD at the bilateral Hegu (LI4, located between the first and second metacarpals, at the midpoint of the radial aspect of the second metacarpal), bilateral Quchi (LI11, located at the lateral end of the transverse elbow stripe, flexing the elbow, at the midpoint of the line connecting the Chize (LU5) and the external humeral epicondyle), bilateral Xuehai (SP10, located on the medial thigh, flexing the knee, 2 cun [≈10 mm] above the medial end of the base of the patella, at the bulge of the medial head of the quadriceps), and bilateral San Yinjiao (SP6, located 3 cun [≈ 10 mm] above the tip of the inner ankle, on the posterior edge of the medial side of the tibia) (Figure 4). After skin disinfection, the acupuncture needles are inserted approximately 10–20 mm into the skin at a 90° angle.

Achieving qi (a combination of sensations, including soreness, numbness, distention, heaviness, and other sensations) is considered an important part of obtaining the efficacy of acupuncture. Four pairs of electrodes are used: two each on bilateral Quchi (LI4) and Hegu (LI11) and two each on bilateral Xuehai (SP10) and San Yinjiao (SP6); they are all ipsilateral to one another. The duration of the EA stimulation is 30 min, with the current intensity of 1–5 mA with a continuous wave of 20 Hz (with the skin around the acupoints shivering mildly without pain). For 2 weeks straight, the participants will have three therapy sessions each week for a total of six sessions.

Participants in the SEA group will receive SEA with PSD but without energizing the electropuncture device. Procedures, electrode placements, and other treatment settings will be the same as those in the EA group but with no electricity output.

Participants in the SAC group will receive sham acupuncture with PSD and PSN at sham acupoints (non-meridian and non-acupuncture points). The sham acupoints selected for this study, based on reports from other scholars, are as follows: (33) The sham Hegu (LI11) is located at the dorsum of the hand, between the first and second metacarpals, 1 cun [≈10 mm] next to the midpoint of the radial side of the second metacarpal. The sham Quchi (LI4) point is at the midpoint between the locations of verum Quchi and Chize; the sham Xuehai (SP10) point is 1 cun [≈10 mm] lateral to the verum Xuehai; the sham San Yinjiao (SP6) point is at 3 cun [≈10 mm] above the tip of the lateral ankle, between the stomach and bile meridians.

Procedures, electrode placements, and other treatment settings will be the same as those in the EA group, but with no skin penetration, electricity output, or needle manipulation to achieve qi.

All study data, including informed consent forms, will be collected and maintained in a dedicated database for medical research records and must be submitted by researchers at the end of the treatment phase. The principal investigators at the participating hospitals will be responsible for collecting the medical research records from the researchers and for reviewing and storing these records.

The data report adopts an electronic Case Report Form (eCRF); each center will assign a specific person to data entry. To ensure the quality and consistency of the source data and database input, two researchers will independently verify the source data with the eCRF data. In the case of any discrepancy, a query list will be created, and the researchers must respond to the query list to resolve the discrepancy. All documentation related to quality control will be maintained to allow for future objective evaluation of safety and critical efficacy outcomes.

Professional statisticians developed a statistical analysis plan upon consultation with the primary investigators. The data will be stored in the Data Management Center of Jiangsu Famous Medical Technology Co. Ltd. and processed by in-house statisticians blinded to group allocation.

All statistical analyses are performed using R [version 4.1.3; R Core Team (2022). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria²]. Statistical significance is set at value of p < 0.05. The intention-to-treat analysis population, consisting of all participants who pass the randomization stage, will be the primary population for demographic and other baseline characteristics, compliance, efficacy analysis, and safety analysis.

The analytical methods will be combined with descriptive and comparative analyses. Qualitative data will be described by frequency tables, percentages, or composition ratios; comparative analyses will be conducted using the chi-squared test, Fisher’s exact test, Wilcoxon rank-sum test, Cochran–Mantel–Haenszel test, and weighted least-squares covariance. Quantitative data will be described as the mean, standard deviation, median, quartile, minimum, and maximum. The t-test will be used for comparative analysis of data with normal distributions and with Satterthwaite correction if the variance is uneven. Quantitative data exhibiting a non-normal distribution on the Wilcoxon rank-sum test will be analyzed using the Wilcoxon signed-rank sum test and covariance generalized linear models. A sensitivity analysis for the primary outcome with the most conservative data (the worst or best outcome of that indicator in the group) will assess the robustness of the missing data at random assumption. A multiple imputation will be used to impute missing values.

The hypothesis test is two-sided; the test statistics and their corresponding p-values will be reported.

The patients and the public will not be involved in the design, conduct, reporting, or dissemination plans of our research.