Repeated Transcranial Magnetic Stimulation for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized Clinical Trial

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.

• Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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） [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment.]
• Methane-hydrogen breath test [Срок оценки: Assessment time points were: baseline (pre-treatment), end of the 3-week treatment, and post-treatment weeks 4, 8 and 12.]