Repeated Transcranial Magnetic Stimulation for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Clinical Trial (rTMS)
Repeated Transcranial Magnetic Stimulation (rTMS) for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Clinical Trial
Objectives: This study aims to evaluate the clinical efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the potential underlying mechanisms by which rTMS alleviates clinical symptoms in IBS-D patients.
Design: This is a clinical trial that uses clinical symptom scales to assess the therapeutic effect of rTMS on IBS-D patients. Meanwhile, gut microbiota and metabolite profiling, as well as the methane-hydrogen breath test, will be applied to investigate the mechanism of action from the perspectives of gut microecology, intestinal motility, and metabolism, so as to provide scientific evidence for the clinical application of rTMS in the treatment of IBS-D.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
Background: A large number of studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) can alleviate chronic pain. Its potential mechanisms include modulating cortical excitability, improving cerebral blood flow and metabolism, regulating neurotransmitters and gene expression, and inducing neuroplasticity. Previous findings indicate that the gut-brain neural circuit involving the insular cortex and anterior cingulate cortex serves as a key pathway regulating chronic visceral pain in irritable bowel syndrome (IBS). Studies have also shown that transcranial magnetic stimulation (TMS) can reduce visceral hypersensitivity in patients with IBS. On this basis, the present study further investigates whether rTMS can improve diarrheal symptoms in patients with diarrhea-predominant irritable bowel syndrome (IBS-D), in order to provide a more reliable and effective therapeutic strategy for clinical practice.
Objectives:
This study aims to evaluate the overall clinical efficacy of rTMS in the treatment of IBS-D, including diarrhea, abdominal pain, quality of life, psychiatric symptoms (anxiety and depression), and sleep disturbance. Meanwhile, the underlying mechanisms of rTMS will be explored using gut microbiota and metabolomic profiling, as well as the methane-hydrogen breath test.
Methods:
This is a clinical trial designed to evaluate the efficacy of rTMS in treating chronic diarrhea in IBS-D patients. A total of 46 IBS-D patients meeting eligibility criteria will be randomly assigned to receive either real rTMS (n=23) or sham rTMS (n=23).
The treatment will last for 3 weeks. The real rTMS group will receive 1 Hz stimulation, 20 minutes per session. The sham rTMS group will receive 0 Hz stimulation (sham condition), 20 minutes per session.
Low-frequency rTMS (1 Hz) will be applied over the medial prefrontal cortex (mPFC) using a magnetic stimulator manufactured by Wuhan IRide Company. Stimulation intensity will be set at 80% of the resting motor threshold (RMT). RMT is defined as the minimal stimulus intensity required to evoke a motor evoked potential (MEP) amplitude of ≥50 μV in at least 5 out of 10 consecutive trials.
The coil will be placed tangentially over the mPFC. Patients will remain seated quietly with minimal head movement during the entire session.For the real rTMS group: 1 Hz frequency, 80% RMT intensity, 1100 pulses per session, with each pulse train lasting 2 seconds, and a total session duration of 20 minutes.For the sham rTMS group: the coil is positioned identically but without effective magnetic stimulation, while pre-recorded sound is played to mimic the acoustic feedback of real rTMS.
Outcome Assessments:
Clinical assessments will include diarrhea, abdominal pain, quality of life, intestinal sensitivity, mood status, and sleep.
Mechanistic evaluations will be performed using gut microbiota and metabolite analysis, combined with methane-hydrogen breath test, to explore the mechanisms underlying rTMS effects on chronic diarrhea in IBS-D patients.
Gut microbiota data will be analyzed to compare differences between the treatment and control groups before and after intervention. Correlation analyses will be conducted between clinical improvement and changes in microbial and metabolic profiles.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Xiuji Kan
- Telefonní číslo: 15339525666
- E-mail: xiujikan@163.com
Studijní místa
-
-
Jiangsu
-
Suzhou, Jiangsu, Čína, 215006
- Nábor
- The First Affiliated Hospital of Soochow University
-
Kontakt:
- Wu Shuangjie
- Telefonní číslo: +8651267972743
- E-mail: sdfyec@163.com
-
Vrchní vyšetřovatel:
- Xiuji Kan
-
Vrchní vyšetřovatel:
- Ruixia Weng, Dr
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
Inclusion Criteria:
Eligible participants had to be between 18- 60 years of age and fulfill the Rome IV criteria for IBS-D. Specifically, patients must have experienced recurrent abdominal pain at least one day per week in the last three months, with symptom onset at least six months prior to diagnosis, associated with defecation or a change in the frequency or form (appearance) of stool. More than 25% of stool episodes be classified as Bristol Stool Form Scale (BSFS) type 6 or 7, and fewer than 25% as type 1 or 2. In addition, patients were required to exhibit moderate to severe symptoms, defined as an Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) score greater than 175 (on a 500-point scale). Dietary preferences of all participants included non vegetarian options and participants maintain stable dietary habits for at least one month prior to randomization. Moreover, patients aged over 50 were required to provide documentation of a normal colonoscopy performed within the preceding three years.
Exclusion Criteria:
The exclusion criteria included a completion rate of daily diaries of less than 50% during the screening period, a history of organic gastrointestinal disease, such as inflammatory bowel disease, a history of surgical resection of the GI tract or cholecystectomy, a recent diagnosis of Helicobacter pylori infection within the past 2 years, a history of gluten or lactose intolerance, a history of malignancy, or a history of neurological or psychiatric conditions. Additionally, individuals with severe systemic diseases, including uncontrolled diabetes mellitus, hyperthyroidism, or severe hepatic, renal, or cardiac insufficiency, were excluded. The use of probiotic or prebiotic supplements, antibiotics (including rifaximin), prokinetic or antidiarrheal agents, tricyclic antidepressants, or immunosuppressive therapies was not permitted within 4 wk prior to screening. Prohibited conditions during the study period included pregnancy, lactation, or being within 12 months postpartum. Lastly, participants with severe needle phobia, metal allergies, implanted cardiac pacemakers, or a known allergic diathesis were excluded. All participants provided their voluntary, written, informed consent prior to their inclusion.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Falešný srovnávač: skupina s falešnou (sham) repetitivní transkraniální magnetickou stimulací
Pro skupinu s falešnou rTMS byla cívka umístěna nad mPFC s vypnutou funkcí rTMS a byly přehrávány předem nahrané akustické artefakty, aby napodobily sluchový zážitek skupiny s rTMS.
|
For the sham rTMS group, the coil was placed over the mPFC with the rTMS function disabled, and pre-recorded acoustic artifacts were played to mimic the auditory experience of the rTMS group.
Ostatní jména:
|
|
Aktivní komparátor: repeated transcranial magnetic stimulation group
The rTMS group was given 1 Hz/s for 20 minutes for 3 weeks.
|
Patients with IBS-D received repetitive transcranial magnetic stimulation at 1 Hz/s for 20 minutes for 3 weeks.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Composite response rate
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
The primary outcome measure of this study is the composite response rate on Day 14 of treatment; a composite responder is defined as having both a ≥30% reduction in the weekly average of the worst abdominal pain intensity in the past 24 hours compared with baseline and a ≥50% reduction in the weekly number of days with Bristol Stool Form Scale (BSFS) Type 6 or 7 (diarrheal stools) compared with baseline.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS)
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
Changes in the total score of the Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) from baseline to Day 21.
The IBS-SSS ranges from 0 to 500 points and covers five domains: severity and frequency of abdominal pain, bloating, satisfaction with bowel habits, and impact on quality of life.
A reduction of ≥95 points is considered a clinically meaningful improvement.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
|
Irritable Bowel Syndrome Quality of Life (IBS-QOL)
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
IBS-QOL is a validated questionnaire assessing quality of life in IBS patients.
Scores range 0-100; higher scores reflect better quality of life.
A ≥14-point increase indicates clinically significant improvement.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
|
The Bristol Stool Form Scale (BSFS) and Frequency of defecation
Časové okno: Assessment time points were: baseline (1 week pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
The Bristol Stool Form Scale (BSFS): it is adopted to assess bowel habits, with scores from 1 to 7 corresponding to stool types ranging from hardest to softest, where higher scores indicate more severe diarrhea.
|
Assessment time points were: baseline (1 week pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
|
Numeric Rating Scale (NRS)
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
Numeric Rating Scale (NRS) is an 11-point pain rating scale (0 = no pain, 10 = worst pain).
A ≥30% decrease in NRS score indicates clinically significant pain relief.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
|
The Visceral Sensitivity Index (VSI）
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
The Visceral Sensitivity Index (VSI): the questionnaire is a 15-item scale used to assess visceral sensitivity.
The total score ranges from 0 to 75 points, with higher scores indicating greater visceral sensitivity.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
|
Patient Health Questionnaire-9 (PHQ-9)
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
The PHQ-9 is a 9-item validated self-rating scale used to screen and assess the severity of depressive symptoms.
Each item is rated on a 4-point Likert scale over the past two weeks.
Total scores range from 0 to 27, with higher scores indicating more severe depressive symptoms.
It is widely applied in clinical trials and gastroenterology studies to evaluate emotional comorbidity in IBS patients.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
|
Generalized Anxiety Disorder-7 (GAD-7)
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
The GAD-7 is a 7-item validated self-reported questionnaire for screening and quantifying the severity of generalized anxiety symptoms.
Participants rate symptom frequency over the preceding two weeks on a 4-point scale.
Total scores range from 0 to 21; higher scores represent greater anxiety severity.
It is routinely used to evaluate anxiety burden in functional gastrointestinal disorders.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
|
Pittsburgh Sleep Quality Index (PSQI)
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
The PSQI is a validated 19-item self-assessment tool evaluating overall sleep quality over the past one month.
It covers seven components: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping medication, and daytime dysfunction.
The global PSQI score ranges from 0 to 21, with higher scores indicating poorer sleep quality.
It is the gold standard for assessing sleep disturbance in clinical research.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8, and 12.
|
|
Gut microbiota and metabolites
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment.
|
Gut microbiota refers to the complex community of microorganisms colonizing the human intestinal tract.
Their metabolites are bioactive substances produced by microbial fermentation, including short-chain fatty acids, bile acid metabolites, amino acid derivatives and other small-molecule compounds.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment.
|
|
Methane-hydrogen breath test
Časové okno: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
The methane-hydrogen breath test is a non-invasive respiratory detection method used to evaluate small intestinal bacterial overgrowth (SIBO) and intestinal transit function.
It detects exhaled hydrogen and methane gas produced by intestinal microbial fermentation.
|
Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.
|
Spolupracovníci a vyšetřovatelé
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 2025-776-01YJ
- BE2023710 (Jiné číslo grantu/financování: Jiangsu Provincial Department of Science and Technology)
- 82470573 (Jiné číslo grantu/financování: National Natural Science Foundation of China)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .