NCT07172139

Transcranial Magnetic Stimulation and Pharmacologic/Probiotic Interventions for Diarrhea-Predominant IBS

Effect of Transcranial Magnetic Stimulation vs Sham Stimulation Combined With Pinaverium Bromide vs Bifidobacteria in Diarrhea-Predominant Irritable Bowel Syndrome: A 2×2 Factorial Randomized Clinical Trial

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 140 (estimated)
• Sponsor: Rui Li · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

What is the study about? This study is for adults with diarrhea-predominant irritable bowel syndrome (IBS-D) who suffer from chronic visceral pain. We aim to investigate whether combining two different treatment approaches is more effective in alleviating IBS-D symptoms than either treatment alone. The first treatment is a non-invasive brain stimulation technique called repetitive Transcranial Magnetic Stimulation (rTMS), while the second treatment involves either an intestinal antispasmodic medication (Pinaverium Bromide) or a probiotic (Bifidobacterium). What will participants do? Participants will be randomly assigned by a computer to one of four groups: 1. Group 1: Receive real rTMS sessions + take Pinaverium Bromide pills. 2. Group 2: Receive real rTMS sessions + take Bifidobacterium pills. 3. Group 3: Receive fake (sham) rTMS sessions + take Pinaverium Bromide pills. 4. Group 4: Receive fake (sham) rTMS sessions + take Bifidobacterium pills. Neither the participant nor the doctor giving the treatments will know which group the participant is in for the rTMS part (this is called "blinding"). The study will involve several weeks of treatment and follow-up visits to track symptoms. What are the potential benefits and risks? Potential Benefits: Participants may experience a reduction in their abdominal pain, diarrhea, and other IBS symptoms. However, benefit cannot be guaranteed. The information from this study may help other IBS patients in the future. Potential Risks: rTMS is generally safe but may cause mild headache, scalp discomfort, or lightheadedness. The medications may have side effects like any drug, which will be explained in detail before the study starts. Why is this study important? This is the first study to test how brain stimulation and gut-focused treatments work together for IBS pain. The results could lead to new and more effective combination therapies for people who don't get enough relief from current treatments.

Detailed description

This is a multicenter, randomized, double-blind, sham-controlled, 2x2 factorial trial investigating the efficacy of combining repetitive Transcranial Magnetic Stimulation (rTMS) with gut-directed therapy for chronic visceral pain in diarrhea-predominant irritable bowel syndrome (IBS-D). Scientific rationale: Current treatments for IBS-D often provide inadequate relief. rTMS, a non-invasive neuromodulation technique, may alleviate pain by restoring cortical excitability and neural plasticity. Its potential synergy with gut-targeted agents (antispasmodic or probiotic) remains unexplored. Objectives: The primary objective is to determine the interaction effect between rTMS (real vs. sham) and drug (pinaverium bromide vs. bifidobacterium) on the composite response rate at Week 2. Secondary objectives include assessing changes in IBS-SSS, IBS-QoL, PHQ-9 scores, and anorectal manometry parameters. Methodology: 140 eligible adults will be randomized equally into four groups: (1) real rTMS + pinaverium bromide, (2) real rTMS + bifidobacterium, (3) sham rTMS + pinaverium bromide, (4) sham rTMS + bifidobacterium. Real rTMS will be delivered at 1Hz, 80% MT over the mPFC for 20 minutes daily for 2 weeks. Sham rTMS uses a placebo coil. Pinaverium bromide (50mg tid) and bifidobacterium (500mg bid) will be administered with matched placebos to maintain blinding. Participants, outcome assessors, and statisticians will be blinded to intervention assignments. Outcomes: The primary outcome is the proportion of participants achieving composite response (≥30% reduction in worst abdominal pain AND ≥50% reduction in days with BSFS 6/7 stools) at Week 2. Secondary outcomes include changes from baseline in IBS-SSS, IBS-QoL, PHQ-9, and manometry measures. Statistics: A factorial ANOVA will be used to test the main and interaction effects. The primary analysis will follow the intention-to-treat principle.

Conditions

• IBS (Irritable Bowel Syndrome)

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Active rTMS + Pinaverium Bromide	A figure-of-eight coil is used to apply active low-frequency (1 Hz) rTMS to the corresponding representation area of the prefrontal cortex (mPFC). The treatment is administered for 20 minutes daily for a total of 2 weeks.
COMBINATION_PRODUCT	Active rTMS + Bifidobacterium	Bifidobacterium animalis subsp. lactis BB-12, provided in capsule form. Each capsule contains a minimum of 5 billion colony-forming units (CFU). Administered orally at a dosage of one capsule twice per day, with meals, for a duration of 2 weeks. The product will be stored refrigerated as per manufacturer's instructions.
COMBINATION_PRODUCT	Sham Comparator: Sham rTMS + Pinaverium Bromide	Pinaverium Bromide 50 mg film-coated tablets. Administered orally at a dosage of 50 mg (one tablet) three times daily, 30 minutes before meals, for a duration of 2 weeks.
COMBINATION_PRODUCT	Placebo Comparator: Sham rTMS + Bifidobacterium	Description: Sham stimulation is delivered using a placebo coil that mimics the sound and sensation of active rTMS but does not deliver the full magnetic field. Parameters identical to active arm.

Timeline

• Start date: 2025-09-01
• Primary completion: 2026-04-01
• Completion: 2026-05-01
• First posted: 2025-09-15
• Last updated: 2025-09-15