A Clinical Trial of Electro-acupuncture for Treating Gallstone Diseases
A Clinical Trial of Electro-acupuncture for Treating Gallstone Diseases
Background: Electro-acupuncture (EA) is commonly used as an alternative treatment for
 gallstone disease. This study aimed to investigate the effectiveness of EA. If shown
 effective, patients could preserve their gallbladders from cholecystectomy.

 Methods: Within a treatment period of 10 weeks, 132 subjects with symptomatic gallstone
 diseases (size <=8mm) were randomly allocated into either treatment group (n=66), or control
 group (n=66). Treatment group was offered 20 EA sessions while the control group were
 clinically observed. The primary outcome was the proportion of patients with total/partial
 clearance of gallstone confirmed by ultrasonography between the two groups. Secondary
 outcomes were the evaluation of Patients Reported Outcomes (PROs) (e.g.SF6D, GIQLI) collected
 throughout the treatment period.
Introduction:

 Gallstone disease is a significant health problem affecting 10%-15% of the adult population.
 Gallstone diseases include cholelithiasis, choledocholithiasis or intrahepatic gallstones. In
 Hong Kong, gallstones are found in 2-3% of the population and 20% of the gallstones are
 symptomatic. To date, cholecystectomy is the gold standard treatment for acute cholecystitis.
 Laparoscopic cholecystectomy is the preferred modality for elective cholecystectomy and is
 advised mainly for symptomatic gallstones such as acute cholecystitis or biliary
 pancreatitis. It is recommended that the cholecystectomy should be performed within weeks
 after resolution of any episode of complications. However, in Hong Kong, the average waiting
 time for cholecystectomy ranged from 9 months to years. The prolonged waiting time increases
 the risk of severe complications such as high conversion rate of acute inflammation,
 pancreatitis, cholecystitis; obstructive jaundice or gallbladder cancer.

 Acupuncture has been extensively applied in clinical practice to treat symptomatic gallstone
 diseases in the ancient Traditional Chinese Medicine (TCM) diagnoses of hypochondrite pain ,
 jaundice or pyretic thoracic retention. The mechanism of acupuncture had been studied with
 (1) increasing of the excretory function of gall bladder; (2) increasing the relaxation of
 the sphincter of Oddi and (3) increasing the secretion of bile. All the above actions aim at
 promoting the spontaneous clearance of gallstones from the biliary system to the gut. In
 fact, gallstone clinic are commonly available in acupuncture department of Chinese Medicine
 Hospitals in China for daily practice. Owing to the poor clinical trial methodology, the
 evidence of effectiveness of acupuncture were not well established yet.

 As a highly recognized traditional therapy, acupuncture has been increasingly used for the
 treatment of pain. Early studies in both animals and human subjects found that
 electroacupuncture (EA) stimulation on certain acupoints could induce the release of
 endogenous opioid peptides and modulate the activities of related receptors in the brain.
 These opioid peptides mainly include endomorphin, β-endorphin, enkephalins, and dynorphin.
 Furthermore, EA stimulation also could modulate central neurotransmitters, including
 serotonin and dopamine, which play important roles in pain signal processing. In addition, it
 was found that EA can help antagonize smooth muscle relaxation. Based on these findings, EA
 may be useful in fostering the expelling effect of the smooth muscle of the gallbladder.

 There had been case reports and case series supporting the use of EA in the treatment of
 symptomatic gallstones. However, only one controlled trial has reported EA in treating
 gallstone diseases on 120 patients with total excretion of gallstones with confirmed with
 ultrasonography (Treatment group 30% vs control group 16.7%, p<0.05) with stone size smaller
 than 1cm. However, this study did not report any adverse event during the course of
 treatment. Apart from absence of adverse events reporting, the reference study did use the
 percentage of patients with total excretion of gallstone confirmed by ultrasound scanning as
 the primary outcome. Bearing in mind safety as the first priority, the study did not adopt
 any blinding in the clinical trial and could overestimate the effectiveness of acupuncture in
 treating gallstone diseases. With our proposed rigorous conduction of clinical trial in terms
 of objective assessment of primary outcome and the blinding of assessor, the investigators
 hope to confirm the effectiveness of acupuncture in gallstone diseases despite of the results
 published in China. In fact, many patients in Hong Kong are waiting for cholecystectomy with
 average time of 9 months to years owing to the less urgency of the operation. The
 investigators hope this study could confirm the effectiveness of acupuncture on gallstone
 diseases so as to develop more evidence. To substantiate the effectiveness and safety of EA
 as an alternative intervention for symptomatic gallstones in clinical practice, this study
 aims at pioneering a well-designed, long-term, large-scale controlled trial for further
 evaluation of the effectiveness of EA in treating gallstone diseases.

 Aims: to evaluate the effectiveness and safety of EA as an alternative treatment in
 symptomatic gallstone diseases. Based on the pragmatic nature of the trial, this study will
 also explore the health economic evaluation of additional acupuncture services against usual
 care.

 Methods: A two arm pragmatic randomized controlled trial design will be conducted at the
 Prince of Wales Hospitals. 132 patients diagnosed of symptomatic gallstone diseases are on
 waiting list for cholecystectomy or being recommended to have cholecystectomy by surgeons
 will be allocated in either EA group (n = 66); or control group (n=66). Treatment group will
 be offered 20 sessions of EA in 10 weeks, while the control group will remain in the usual
 care for solely assessment. Primary outcome is the proportion of patients with total
 clearance of gallstones after treatment with confirmation by ultrasonography. The secondary
 outcome is the monitoring the incidence of common bile duct stone by liver function test
 (LFT) and MRCP.

 Implication of this study The most expected and clinically significant findings should be the
 exploratory effectiveness of EA that promotes the excretion of the gallstones. In addition,
 if EA is found to be effective, results from this study can form a solid basis for funding
 routine establishment of an EA service care model for among symptomatic gallstone diseases
 patients. Based on the pragmatic nature of the trial, this study will also explore the health
 economic evaluation of additional acupuncture services against usual care which could
 facilitate to give an overview for setting up to the integrative medical service.

 Aims and Hypotheses to be Tested:

 This study aims to evaluate the effectiveness and safety of EA in the treatment of
 symptomatic gallstone diseases compare with usual care

 Hypotheses:

 EA could produce greater effects than usual care in treating symptomatic gallstone diseases
 and increase the rate of excretion.

 Objectives

 1. To determine whether EA treatment is more effective than usual care in the management of
 symptomatic gallstone diseases; and

 2. To determine whether EA, compared with usual care, can increase clearance rate as
 confirmed by ultrasonography,

 3. To determine the safety of EA in the management of gallstone diseases

 4. To explore the health economic assessment of both EA and usual care
Inclusion Criteria:

 1. Patients aged 18 to 70 years of age who are diagnosed of gallstone diseases with the
 last observable ultrasonography.

 2. Patients with symptoms such as recurrent biliary colic

 3. Wait-listed for elective cholecystectomy or being recommended to have cholecystectomy
 by surgeons.

 4. Largest gallstone size of smaller than 0.8cm.

 Exclusion Criteria:

 1. Gallstones with the size that cannot be assessed precisely by ultrasound

 2. Any gallstone larger than 0.8cm

 3. Poor gallbladder ejection fraction computed from Ultrasound-determined fasting and
 post-prandial gallbladder volumes

 4. Contraindication to MRI

 5. Patients contraindicated for ERCP

 6. Cardiovascular disease with decompensation (New York Heart Association class III or
 IV)

 7. Pregnancy or breastfeeding

 8. Alcoholism

 9. Intravenous drug users

 10. Needle phobia;

 11. Unable to respond consistently in trial-out questions of the questionnaire;

 12. Refused to provide written informed consent for joining the study