Improvement of Postoperative Immunosuppression in Patients Receiving Coronary Artery Bypass Grafting by TEAS

Study Overview
=================
Brief Summary
-----------------
The coronary artery bypass grafting (CABG) is a surgery to relieve angina and reduce mortality of coronary heart disease. However, the patient is more prone to have immunosuppression after the surgery, causing secondary infection, and it is closely correlated to the occurrence and progress of tumor after surgery. More and more studies revealed that needle puncture was able to effectively regulate the function of immune system. However, its perioperative application is unclear. Therefore, this clinical study is aimed to evaluate whether the effect of transcutaneous acupoint electric stimulation (TEAS) on improvement of immunosuppression of patients after receiving CABG.

Detailed Description
-----------------
This clinical study was a single-center clinical trial. The 88 patients scheduled to receive CABG under CPB were randomized into 2 groups: the group of TEAS, and the group of transcutaneous acupoint pseudo - electric stimulation (Sham TEAS). Monocytic HLA-DR expression serves as a primary endpoint, and other laboratory parameters (e.g. IL-6, IL-10) and clinical outcomes (e.g. postoperative infectious complications, ICU stay time, and mortality) as the secondary endpoints. In addition, some immune indicators, such as high mobility group protein 1 (HMGB1) and regulatory T cell (Treg), possibly related to the mechanism of TEAS, will also be measured. This study is a preliminary, mono-center, double-blind, randomized and controlled clinical trial (number of sample, n=88) to explore the effects of TEAS therapy on improvement of postoperative immunosuppression indicated by diminished HLA-DR expression of patients receiving CABG (Fig. 1). The trial will be commenced after ethical approval has been obtained from the Ethics Committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. All study-related procedures will be performed only after subjects have given their written informed consent. The trial is designed following the Consolidated Standards of Reporting Trials (CONSORT) guidelines, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist (Additional file 1), and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) recommendations. We calculate the sample size from the pilot study in our hospital based on the primary outcome Human leukocyte antigen of monocyte (mHLA-DR). In the study, the expression of mHLA-DR three days after surgery was (36.17±5.42) % in the TEAS group and (27.33±3.50) % in the Sham TEAS group, with a power of 80% and 5% Type I error rate. Assuming that the dropout rate to be 10%, 88 patients (n=44 for each group) are needed. Patients will be recruited from the department of Thoracic and Cardiovascular surgery, at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Potentially eligible subjects who have scheduled for CABG under CPB for coronary diseases will be invited to participate. Patients will be referred from a cardiothoracic surgeon, and then a research assistant will approach the subjects in the general ward pre operation. Patients will be screened and consented for the study. Following the consent, eligible participants will be block randomized into two groups: ⑴ TEAS group (n=44) and ⑵ sham TEAS group (n=44). All patients will conduct a standard operative procedure and postoperative analgesia management. The patients of TEAS group will receive TEAS therapy in perioperative period, and the Sham TEAS will not be performed to receive electrical stimulation sensation in perioperative period. Assessments will be conducted during the perioperative period until 30 days after surgery.

Official Title
-----------------
Improvement of Postoperative Immunosuppression in Patients Receiving Coronary Artery Bypass Grafting by Transcutaneous Electrical Acupoint Stimulation: Study Protocol for a Double-blind Randomized Controlled Trial

Conditions
-----------------
Immunosuppression

Intervention / Treatment
-----------------
* Device: TEAS+GA group
* Device: Sham TEAS+GA group


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Aged 18-75 years, male and female; Patients diagnosed as coronary disease, scheduled to receive CABG; BMI: 18.5kg/m2<BMI≤30kg/m2； Graded as I-III by American Standards Association(ASA); Patients firstly receiving CABG under extracorporeal circulation. Exclusion Criteria Presence of surgical incision or scar at Zusanli acupoint (ST36) /Shenshu (BL23) acupoint; Patients with local skin infection at acupoint; Patients with nerve injury on upper or lower limbs; Patients with history of spinal surgery; Patients who have participated in other clinical trial in recent 4 weeks; Patients using pacemaker; Patients combined with pain before surgery who are using central analgesic drug or drug abuser (e.g., opioid) and dependent user; Patients combined with severe central nervous system disease or severe mental disease; Patients with alcoholic history; Patients who have received emergent coronary bypass operation due to acute myocardial infarction.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEAS+GA group<br>The patients of TEAS+GA group will receive TEAS therapy in perioperative period. GA: general anesthesia | Device: TEAS+GA group<br>* The acupoints including Zusanli and Shenshu, were identified before electrical stimulation with surface electrodes. Selection of these acupoints was based on a consensus between the acupuncturists of the study.<br>Device: Sham TEAS+GA group<br>* No electrical stimulation sensation is performed in the Sham TEAS group. In the Sham TEAS group, pseudo-stimulation is provided by deliberately connecting the electrodes to the incorrect output socket of the electroacupuncture device, and thus there is no flow of electric current. Patients could see the output light flashing but no current was transmitted throughout the procedure. Patients would be told that the stimulation frequency selected was not perceivable by human beings.<br>|
| Sham Comparator: Sham TEAS+GA group<br>The patients of Sham TEAS+GA will receive none TEAS in perioperative period. | Device: TEAS+GA group<br>* The acupoints including Zusanli and Shenshu, were identified before electrical stimulation with surface electrodes. Selection of these acupoints was based on a consensus between the acupuncturists of the study.<br>Device: Sham TEAS+GA group<br>* No electrical stimulation sensation is performed in the Sham TEAS group. In the Sham TEAS group, pseudo-stimulation is provided by deliberately connecting the electrodes to the incorrect output socket of the electroacupuncture device, and thus there is no flow of electric current. Patients could see the output light flashing but no current was transmitted throughout the procedure. Patients would be told that the stimulation frequency selected was not perceivable by human beings.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of mHLA-DR positive cell | Human leukocyte antigen of monocyte (mHLA-DR) | day before surgery, Day 1 after surgery (one day after surgery), Day 3 after surgery (3 days after surgery), and Day 5 after surgery (5 days after surgery). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Content of serum IL-6 | interleukin-6 (IL-6) | One day before surgery, Day 1, 3 and 5 after surgery | 
| Content of serum CRP | reactive protein C (CRP) | One day before surgery, Day 1, 3 and 5 after surgery | 
| Rate of secondary infection | observe the incidence of incision infection, lung infection, hematogenous infection and indwelled catheter infection after the surgery | Within 7 days after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
immunosuppression, cardiac surgery, TEAS(Transcutaneous electrical acupoint stimulation), postoperative