Clinical trial NCT03891147: A Clinical Trial of Electro-acupuncture for Treating Gallstone Diseases
Official title: A Randomized, Single-blind, Controlled Trial of Electroacupuncture for the Treatment of Symptomatic Gallstone Diseases
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gallstones
Keywords: symptomatic gallstone diseases
electro-acupuncture
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Food and Health Bureau, Hong Kong
First posted: 2019-03-26
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: Change of gallstones (excretion of gallstones confirm by ultrasound)
timeFrame: Baseline and 10th week
Secondary outcomes:
measure: Change of Gastrointestinal Quality of Life instrument (GIQOLI)
timeFrame: Baseline and 10th week
measure: 132 subjects with Liver function test
timeFrame: Baseline, 5th and 10th week
measure: Clear common bile duct confirm by MRCP
timeFrame: After 10th week if number of gallstones reduced(confirm by ultrasound)
measure: Number of cases of Serious Adverse Event reported by any subjects
timeFrame: Baseline-10th weeks
measure: Change of EQ-5D
timeFrame: Baseline, 5th week and 10th week
measure: Change of EQ VAS
timeFrame: Baseline, 5th week and 10th week
measure: Change of SF-6D
timeFrame: Baseline, 5th week and 10th week
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: The Chinese University of Hong Kong
state: Hksar
Study officials:
affiliation: HKIIM, CUHK
name: Wendy Wong, Dr
role: PRINCIPAL_INVESTIGATOR
References: