Clinical trial NCT05920395: Mechanisms of Electroacupuncture for Functional Dyspepsia Based on "Enterotypes" and Metabolomics
Official title: Mechanisms of Electroacupuncture for Functional Dyspepsia Based on "Enterotypes" and Metabolomics
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Functional Dyspepsia
Keywords: Functional Dyspepsia
Electroacupuncture
Intestinal flora
Lead sponsor: Wuhan Central Hospital
Sponsor class: OTHER
First posted: 2023-06-27
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to explore the clinical efficacy and possible mechanisms of electroacupuncture treatment for functional dyspepsia (FD). The main question it aims to answer are:

* Differences in the effects of electroacupuncture and sham electroacupuncture intervention on FD.
* Differences in gastrointestinal hormone levels and gut microbiota and their metabolites between healthy individuals and FD patients.

Participants receive electroacupuncture and sham electroacupuncture interventions respectively. Before and after the intervention, the clinical symptom score, gastrointestinal symptom evaluation scale, gastrointestinal symptom score questionnaire, and functional dyspepsia quality of life scale of the subjects will be observed. The levels of gastrointestinal hormones MTL, Ghrelin, 5-HT, CCK, PYY, and GLP-1 will be measured, as well as the changes in microbial diversity and SCFAs in their metabolites in feces, A follow-up visit will be conducted one month after the intervention for all participants.

Detailed description: Functional dyspepsia (FD) is a common and difficult clinical disease, and there is currently no effective treatment plan. Electroacupuncture is commonly used in clinical practice, but there is a lack of high-quality clinical evidence of its effectiveness. This study explores the clinical efficacy and possible mechanisms of electroacupuncture in the treatment of FD.

The study set up a healthy control group and an FD group. The FD group was divided into PDS type and EPS type according to their classification, and received electroacupuncture and sham electroacupuncture intervention, respectively. Before and after intervention, the clinical symptom score, gastrointestinal symptom evaluation scale, gastrointestinal symptom score questionnaire, and functional dyspepsia quality of life scale of the participants were observed. The levels of gastrointestinal hormones MTL, Ghrelin, 5-HT, CCK, PYY, GLP-1 were measured, and changes in fecal microbiota diversity and SCFAs in their metabolites were also detected. A follow-up visit will be conducted one month after the intervention for all participants.

Experiment 1: Observing the differences in various indicators between healthy individuals and FD patients Grouping: ① Healthy control group: 26 healthy volunteers, without any intervention, were tested for gastrointestinal hormone levels, gut microbiota, and their metabolites.② FD group: A total of 104 patients were included, and the levels of gastrointestinal hormones, gut microbiota, and their metabolites were detected after inclusion. The differences in gut type between the two groups of patients were analyzed.

Experiment 2: Observing the Effect of Electroacupuncture on FD Patients Grouping: The 104 FD patients included as required included 52 PDS type and 52 EPS type. Both types of patients were randomly assigned to the electroacupuncture group and the sham electroacupuncture group, with 26 patients in each group. It is divided into PDS electroacupuncture group (Group A), PDS sham electroacupuncture group (Group B), EPS electroacupuncture group (Group C), and EPS sham electroacupuncture group (Group D).

① Electroacupuncture group: including Group A and Group C, with 26 cases each, all receiving electroacupuncture treatment. The patient lies on his back on the treatment bed. After routine disinfection, a 0.30X50mm or 0.30X40mm disposable sterile acupuncture and moxibustion needle is directly punctured into the acupoint. After getting qi, the needling sensation is maintained by the manipulation of leveling, reinforcing and reducing. Point selection: Zhongwan, Zusanli, Neiguan, and Tianshu, connected to the 6805-AII electroacupuncture treatment instrument; Connect one set of electrodes to Zhongwan and Tianshu acupoints, with the positive electrode connected to Zhongwan acupoint and the negative electrode connected to Tianshu acupoint on one side; Using dense wave pulse stimulation with a frequency of 2Hz/100Hz, with a stimulation intensity that the patient can tolerate, 30 minutes each time, treated once every other day for a total of 4 weeks.

② False electroacupuncture: including group B and group D, with 26 cases each, with shallow acupuncture. After disconnecting the end of the electrode and binding it with black tape, the false electrode was connected without being electrified, and the rest were the same as the electroacupuncture group.

The positioning of acupoints shall refer to the positioning standards in the new century national planning textbook for higher Chinese medicine colleges and universities, "Meridian and Acupoint Science," edited by Shen Xueyong. A follow-up visit will be conducted one month after the intervention for all subjects.

During the intervention, all subjects did not take drug treatment. If the corresponding symptoms of the subjects such as abdominal pain, abdominal burning, early satiety and so on were significantly aggravated, the subjects would be given symptomatic treatment of the emergency drug pantoprazole sodium enteric coated tablets when the investigator diagnosed that drug intervention was needed. Participants can also consider choosing to seek treatment at the gastroenterology outpatient department. If needed, they can assist in contacting a specialist to provide corresponding professional diagnosis and treatment advice. Subjects receiving emergency medication or other medications that affect gastrointestinal motility need to terminate the study. If they have completed 1/2 course of treatment, the corresponding outcome indicators should be included in the efficacy statistics.

Eligibility criteria: FD diagnostic criteria:

Functional dyspepsia diagnostic criteria: According to the Rome IV diagnostic criteria for functional dyspepsia (2016).

Symptoms:①Early satiety; ②Postprandial fullness and bloating; ③Epigastric pain;④ Epigastric burning.

One or more of these four symptoms must be met, and there must be no evidence of structural diseases (including gastroscopy, etc.) that can explain these symptoms. In addition, the detailed diagnostic criteria for postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS) must also be met.

The diagnosis of EPS meets the following criteria.

1. Meeting at least one of the following criteria for at least one day per week.

   ① Postprandial fullness and bloating (of such a degree as to affect daily living);

   ② Early satiety (of such a degree as to result in inability to finish a normal meal).
2. Routine examinations (including gastroscopy) did not reveal any systematic, organic, or metabolic diseases that could explain the above symptoms;
3. Symptoms must have appeared for at least six months prior to diagnosis, and met the above criteria for the past three months.

The diagnostic criteria for EPS include meeting at least one of the following criteria for at least one day per week:

1. Epigastric pain (of such a degree as to affect daily living);
2. Epigastric burning (of such a degree as to affect daily living);
3. Routine examinations (including gastroscopy) did not reveal any systematic, organic, or metabolic diseases that could explain the above symptoms;
4. Symptoms must have appeared for at least six months prior to diagnosis, and met the above criteria for the past three months.

Inclusion criteria

1. Meeting the Western medicine diagnostic criteria for FD;
2. Aged 18-65 years (inclusive of 18 and 65 years old);
3. Not having taken any gastrointestinal prokinetic drugs for at least 15 days before treatment, and not having participated in any other clinical studies;
4. Voluntary signing of an informed consent form for this study. Note: Only patients who meet all four of the above criteria can be included in this study.

Exclusion criteria

1. Pregnant or lactating women;
2. Patients with severe organic digestive system diseases indicated by endoscopic examination, such as severe dysplasia or mucosal erosion, or pathological indication of malignancy;
3. Patients with endocrine, cardiovascular, cerebrovascular, hematopoietic system, or neurological diseases such as diabetes, severe coronary heart disease, hypoglycemia, or hemiplegia;
4. Patients with mental illness,infectious diseases, progressive malignant tumors,or life- threatening diseases;
5. Patients who are afraid of acupuncture, have allergies or are allergic to medical supplies.

Note: Patients who meet any of the above criteria will be excluded.

Removal criteria

1. Cases that are mistakenly included due to concealment of illness information or failure to meet inclusion criteria should be excluded;
2. Participants with poor compliance or those who withdraw from the study on their own during the treatment period, or those who use treatment methods prohibited by this protocol during the study phase;
3. Participants who experience severe adverse events or complications and are unable to continue the treatment, and the trial is terminated;
4. Participants who do not follow the prescribed treatment or whose data is incomplete, affecting efficacy and safety evaluation.

Dropout criteria Participants who have been included but are unable to participate in the trial on time, or who do not follow the trial requirements, or who drop out during treatment.

The handing of exclusion and dropout When a participant drops out, the researcher should contact them as much as possible through house visits, scheduled phone calls, letters, etc., to inquire about the reasons for dropout. record the date of the last treatment, and complete the evaluation items that can be completed. All cases of exclusion and dropout will be subjected to intention-to-treat analysis after the end of the trial.

Research Termination Criteria

1. If the condition worsens during the experiment or other serious illness occurs, it is determined that participation needs to be terminated or other treatments are necessary.
2. If a serious adverse event occurs during the experiment that prevents further participation.
3. The investigator should record the reason and time for withdrawing from the study. Those who have completed more than half of the treatment should be included in the efficacy statistics.

Primary outcomes:
measure: Overall efficacy evaluation
timeFrame: up to 4 weeks
measure: Gastric electrogastrography (EGG) testing
timeFrame: baseline, pre-intervention
measure: Gastric electrogastrography (EGG) testing
timeFrame: up to 4 weeks
Secondary outcomes:
measure: Gastrointestinal Symptom Rating Scale (GSRS)
timeFrame: baseline, pre-intervention
measure: Gastrointestinal Symptom Rating Scale (GSRS)
timeFrame: up to 4 weeks
measure: Gastrointestinal Symptom Rating Scale (GSRS)
timeFrame: up to 8 weeks
measure: Gastrointestinal Symptom Score Questionnaire (GIS)
timeFrame: baseline, pre-intervention
measure: Gastrointestinal Symptom Score Questionnaire (GIS)
timeFrame: up to 4 weeks
measure: Gastrointestinal Symptom Score Questionnaire (GIS)
timeFrame: up to 8 weeks
measure: Nepean Dyspepsia Index (NDI)
timeFrame: baseline, pre-intervention
measure: Nepean Dyspepsia Index (NDI)
timeFrame: up to 4 weeks
measure: Nepean Dyspepsia Index (NDI)
timeFrame: up to 8 weeks
measure: Functional Dyspepsia Quality of Life questionnaire (FDQOL).
timeFrame: baseline, pre-intervention
measure: Functional Dyspepsia Quality of Life questionnaire (FDQOL).
timeFrame: up to 4 weeks
measure: Functional Dyspepsia Quality of Life questionnaire (FDQOL).
timeFrame: up to 8 weeks
measure: Gastrointestinal hormone level testing
timeFrame: baseline, pre-intervention
measure: Gastrointestinal hormone level testing
timeFrame: up to 4 weeks
measure: Intestinal microbiota diversity testing
timeFrame: baseline, pre-intervention
measure: Intestinal microbiota diversity testing
timeFrame: up to 4 weeks
measure: Intestinal microbiota metabolite testing
timeFrame: baseline, pre-intervention
measure: Intestinal microbiota metabolite testing
timeFrame: up to 4 weeks
Other outcomes:
Locations:
Study officials:
References: