The Effect and Mechanism of Acupuncture on Functional Dyspepsia

Study Overview
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Brief Summary
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The aim of the study is to investigate the effect of acupuncture on functional dyspepsia compared with sham control. The study aims to clarify the mechanism of acupuncture by assessing functional magnetic resonance imaging and metabolomics.

Detailed Description
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Functional dyspepsia (FD) is a functional gastrointestinal disorder without any structural lesion. Due to the lack of satisfactory effect of conventional treatments, many FD patients turn to alternative treatments such as acupuncture. Acupuncture, one of the most sought therapeutic modalities in traditional Korean Medicine, has been commonly used for treating gastrointestinal disorders. However, the effect and mechanism of acupuncture on FD has not been rigorously evaluated. In the present study, we will investigate whether 10 sessions of acupuncture over 4 weeks, in comparison with sham acupuncture, improve symptoms of FD and activate regions of brain area. We will also perform metabolomics study to find the mechanism of acupuncture to FD. Outcome measures include proportion of responder, Korean version of Nepean Dyspepsia Index, Functional Dyspepsia-Related Quality of Life, Ways of Coping Question, Coping Strategy Questionnaire, Perception of bodily sensation, The State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression Scale, functional magnetic resonance imaging and metabolomic study.

Official Title
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Effect and Mechanism of Acupuncture on Patients With Functional Dyspepsia: a Protocol for a Randomized, Assessor-blind, Sham-controlled Trial

Conditions
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Dyspepsia

Intervention / Treatment
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* Device: Acupuncture
* Device: Sham acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Participants should meet following conditions: Aged of 30 - 49 Individuals who meet FD and postprandial distress syndrome (PDS) criteria in Rome III Individuals who complain the degree of dyspepsia for more than 40 points of visual analogue scale (VAS; 0, no symptom at all; 100, the most severe symptom one ever had) At least 3 questions show more than 2 points in Gastrointestinal impact scale Individuals who have normal esophagogastroduodenoscopy results within a year and no organic diseases which can explain current symptoms such as peptic ulcer, dysplasia, mucosa-associated, lymphoid tissue lymphoma, esophageal cancer, gastric cancer Individuals who are not supposed to take any other treatments associated with FD during the study Individuals who voluntarily agree with a study protocol and sign a written informed consent Exclusion Criteria Participants who report the followings will be excluded: Individuals who have organic diseases such as gastroesophageal reflux disease Individuals who have obvious signs of irritable bowel syndrome Individuals who have alarm symptoms (weight loss, black or tar stool or dysphagia) Individuals who have serious structural disease (disease of heart, lung, liver or kidney) or mental illness Individuals who have had surgery related with the gastrointestinal tract , except for appendectomy more than six months ago Individuals who are pregnant or breastfeeding Individuals who are taking drugs which might affect gastrointestinal tract; minimum wash-out period of 2 weeks is required before participating in the trial Individuals who are HIV-positive Individuals who have a problem of mal-absorption Individuals who have difficulties in attending the trial (eg. paralysis, serious mental illness, dementia, drug addiction, time constraint, severe disorder in vision or hearing, illiteracy, etc.) Individuals who do not want to sign the informed consent Individuals who have other diseases that could interfere acupuncture treatment, e.g. clotting disorders or leukopenia, pace-maker, epilepsy, or anticoagulant therapy Individuals who have metal implants or fragments which might influence fMRI examination

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acupuncture<br>Participants in this group are given 10 times of real acupuncture treatment for 4 weeks. | Device: Acupuncture<br>* Acupuncture rationale 1a) Style of acupuncture: body acupuncture (in accordance with meridian theory) Needling details 2a) Number of needle insertions per subject per session: 13 2b) Acupoints: Basic points - Large Intestine(LI)4, Stomach(ST)36, Liver(LR)3, Pericardium(PC)3, Spleen(SP)4, Stomach(ST)34, Conception Vessel(CV)12, 2c) Depth: 5   30mm 2d) Response sought: 'De qi' sensation; 2e) Needle stimulation: Manipulation 2f) Retention time: 15 minutes 2g) Needle type: 0.2 X 40 mm, sterilized stainless steel needle, Dongbang Inc., Korea<br>* Other names: Acupuncture treatment;|
| Sham Comparator: Sham acupuncture<br>Participants in this group are given 10 times of sham acupuncture treatment for 4 weeks. | Device: Sham acupuncture<br>* The participants in sham acupuncture group are given sham acupuncture treatment at the same acupoints in the same times and method as acupuncture arm. The sham device would be a Streitberger device.<br>* Other names: Streitberger Device;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders | The proportion of patients who answer Yes to more than half of adequate relief questions in the treatment period. Patients are expected to report their response to the acupuncture treatment by answering the following question at each visit: After the last visit, have you had adequate relief of your stomach pain or discomfort? Questions will be asked at each visit during treatment period (Twice a week for 4 wks, total 10 times - 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 wks). Responders are defined as patients reporting adequate relief for at least 50% of the study period (more than 5 times of Yes to adequate relief question out of total 10 questions). The proportion of responder will be compared statistically between intervention groups. | Once in treatment period (4 wks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nepean Dyspepsia Index - Korean version (NDI-K) | The Nepean Dyspepsia Index is a reliable and valid measure of quality of life in FD. The Nepean Dyspepsia Index originally contains 42 items designed to measure impairment of a subjective ability engaged in relevant aspects of their life because of dyspepsia. It was subsequently shortened to 25 items, yielding 5 sub-scales. NDI-K, validated in 2003 by Lee at al., made up of 2 sections which are about symptom-based questions and quality of life. In this trial, symptom-based questions, i.e. questions about period, severity and distressful degree of 15 symptoms, will be evaluated. | treatment (0 wks), After treatment (4 wks) | 
| Functional Dyspepsia-Related Quality of Life (FD-QoL) Questionnaire | The FD-QoL scale is a 21-item Likert-type questionnaire that can easily be completed within 5 min. Short administration time and high comprehensibility supports the feasibility of measuring health-related quality of life. | Before treatment (0 wks), After treatment (4 wks) | 
| Ways of Coping Question (WCQ) | The Ways of Coping Questionnaire (WCQ) (Folkman & Lazarus, 1988) assessed the parents' coping strategies. It has 66-items, each with a 4-point Likert scale indicating the frequency with which the strategy was used. The measure comprises eight scales representing theoretically different coping strategies: confrontative coping, distancing, self-controlling, seeking social support, accepting responsibility, escape-avoidance, problem solving, and positive reappraisal. | treatment (0 wks), After treatment (4 wks) | 
| Coping Strategy Questionnaire (CSQ) | Coping Strategy questionnaire is one of models for measuring stress and coping to help explain the differences in adjustment found among persons who experience chronic pain. It consists of 48 items, each with a 7-point Likert scale (0:never; 3: sometimes; 6:always) and divide into eight scales of six items each; (1) Catastrophizing, (2) Distractor behaviors, (3) Self-instructions, (4) Ignoring the pain, (5) Reinterpreting the pain, (6) Hoping, (7) Faith and praying, (8) Cognitive distraction. | Before treatment (0 wks), After treatment (4 wks) | 
| Functional Magnetic Resonance Imaging ; 3.0T MRI system(Achieva, Philips) | A measure of steady state (REST and PAIN) and blood oxygenation level dependent (BOLD) under the condition of event related design (ACUP) scan run. | Before treatment (0 wks), After treatment (4 wks) | 
| Metabolic profiling of plasma and urine | In order to investigate the biological effects of FD and the effect of acupuncture on metabolism, the blood and urine sample will be analyzed using nuclear magnetic resonance (NMR)-based metabolomic techniques to compare the metabolites such as amino acids, organic acids, and blood sugar of FD patients. | Time Frame: Before treatment (0 wks), After treatment (4 wks) | 
| The Center for Epidemiologic Studies Depression Scale (CES-D) | The Center for Epidemiological Studies-Depression (CES-D), originally published by Radloff in 1977, is a 20-item measure that asks caregivers to rate how often over the past week they experienced symptoms associated with depression, such as restless sleep, poor appetite, and feeling lonely. Response options range from 0 to 3 for each item (0 = Rarely or None of the Time, 1 = Some or little of the time, 2 = Moderately or much of the time, 3 = Most or almost all the time). Scores range from 0 to 60, with high scores indicating greater depressive symptoms. | Before treatment (0 wks), After treatment (4 wks) | 
| The State-Trait Anxiety Inventory (STAI) | The State-Trait Anxiety Inventory (STAI) is a psychological inventory based on a 4-point Likert scale and consists of 40 questions on a self-report basis. The STAI measures two types of anxiety - state anxiety (anxiety triggered by a specific event), and trait anxiety (anxiety derived from personal characteristic). Higher scores are positively correlated with higher levels of anxiety. | Before treatment (0 wks), After treatment (4 wks) | 
| Perception of bodily sensation (PDS) | This scale is a 10-item questionnaire with 6(1-7) point Likert scale. Patients with higher Perception of bodily sensation (PBS) could have a higher emotional or cognitive intolerance to bodily reactions. | Before treatment (0 wks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Functional Dyspepsia, Acupuncture, Functional MRI