Novel Pilot Study to Treat Symptoms of IBS With Diarrhea Using Combination Therapy of a Low-FODMAP Diet and a Neuromodulator

The purpose of this research is to study the added benefit of treating IBS symptoms with a medication called mirtazapine in treating IBS symptoms when paired with a low-FODMAP diet compared to a low-FODMAP diet alone. FODMAP stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. These are short-chain carbohydrates that can cause digestive distress in some people.

You have been asked to take part in this research because you have symptoms of diarrhea-predominant irritable bowel syndrome that may respond to treatment with a combination of a medication called mirtazapine and a low-FODMAP diet.

Study Overview

• Status: Recruiting
• Conditions: Diarrhea; IBS - Irritable Bowel Syndrome
• Intervention / Treatment: Drug: Mirtazapine; Other: Placebo

Detailed Description

We hypothesize that adult patients with IBS-D treated with a combination of a low FODMAP diet and mirtazapine will have a greater improvement in global IBS symptoms including abdominal pain and diarrhea in addition to improved quality of life compared to those treated with a low-FODMAP diet only. Global improvement in IBS symptoms will be evaluated using the validated IBS-SSS questionnaire. We will evaluate changes in quality of life using a validated IBS-QoL questionnaire. We will assess the improvement in abdominal pain using a numerical rating system and assess improvements in diarrhea using the Bristol stool form scale. We will assess responses to bloating using a Mayo bloating questionnaire forms. We will assess improvement in diarrhea using the Bristol stool form scale.

Improvement in anxiety and any other descriptive information as provided by patients including patients reporting impression of overall severity of symptoms at the beginning, middle, and end of study.

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that affects up to 10% of the United States adult population. IBS is characterized by recurrent abdominal pain and altered bowel habits, diagnosed using the Rome IV criteria. Approximately one-third of all IBS patients are classified as having IBS with diarrhea (IBS-D), which has no validated treatment algorithm. The American College of Gastroenterology IBS guideline recommends the low-FODMAP (fermentable oligo-, di-, monosaccharide, and polyol) diet as a safe and modestly effective treatment. An analysis of 7 randomized, controlled trials found that the low-FODMAP diet was associated with an improvement in global IBS symptoms. However, despite following the low-FODMAP diet, many patients have persistent abdominal pain, which can be difficult to treat. The mechanisms underlying chronic abdominal pain in patients with IBS are unknown, although visceral and central hypersensitivity are thought to play a role. No medication is FDA-approved for the treatment of abdominal pain in IBS. Mirtazapine is an atypical antidepressant that acts on several classes of receptors. In a small open-label study mirtazapine improved IBS-D symptoms, including abdominal pain.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jessica C Petrov, MD; Phone Number: 904-953-2000; Email: Petrov.Jessica@mayo.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
      • Contact: Jessica C Petrov, M.D.; Phone Number: 904-953-6970; Email: researchparticipantadvocate@mayo.edu
      • Principal Investigator: Brian Lacy, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must meet all of the inclusion criteria to participate in this study:

  • Adults (ages 18-70)
  • Score of >175 on the IBS-SSS questionnaire
  • Must meet Rome IV criteria for IBS-D
  • If subject is of reproductive capability a negative urine pregnancy test must be available prior to entering the study
  • Ability to understand study procedures and to comply with them for the entire length of the study

Exclusion Criteria:

• All candidates meeting any of the below exclusion criteria at baseline will be excluded from study participation:

  • Score of < 175 on the IBS-SSS
  • Prior diagnoses of: known celiac disease, small intestinal bacterial overgrowth, inflammatory bowel disease, or microscopic colitis
  • Ongoing significant anxiety or depression
  • A history of a known side effect to mirtazapine
  • Prior treatment with a low FODMAP diet or mirtazapine without clinical benefit
  • Active alcohol or drug abuse
  • Inability to read or understand the consent form
  • Any other medical or psychological reason that would prevent active participation in a research study
  • Pregnant females

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mirtazapine Group; Subjects will present at Mayo Clinic through a doctor's appointment and a diagnosis of irritable bowel syndrome will be receiving mirtazapine by pill form.	Drug: Mirtazapine; mirtazapine will be told to use 1 pill 1 hour before bedtime for the first week (7.5 mg po q.h.s.), 2 pills before bedtime during the second week of therapy (15 mg po q.h.s.), 3 pills (22.5 mg po q.h.s.) 1 hour before bedtime for the third week, and 4 pills (30 mg po q.h.s.) 1 hour prior to bedtime for the remainder of the study.; Other Names: Remeron
Placebo Comparator: Placebo Group; Subjects will present at Mayo Clinic through a doctor's appointment and a diagnosis of irritable bowel syndrome will be receiving placebo by pill form.	Other: Placebo; Placebo will be told to use 1 pill 1 hour before bedtime for the first week (7.5 mg po q.h.s.), 2 pills before bedtime during the second week of therapy (15 mg po q.h.s.), 3 pills (22.5 mg po q.h.s.) 1 hour before bedtime for the third week, and 4 pills (30 mg po q.h.s.) 1 hour prior to bedtime for the remainder of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of Irritable Bowel Syndrome	Evaluate global improvement in IBS symptoms using the validated IBS-SSS	49 days
Abdominal Pain Score	Assess improvement in abdominal pain using a numerical rating system	49 days
Stool Form Scale	Assess improvement in diarrhea using the Bristol stool form scale	49 days
Mayo Bloating Scale	Assess response to bloating using a validated Mayo bloating questionnaire	49 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Brian E Lacy, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): December 19, 2026
• Study Completion (Estimated): December 19, 2026

Study Registration Dates

• First Submitted: November 9, 2024
• First Submitted That Met QC Criteria: November 9, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; Diarrhea; IBS
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Colonic Diseases, Functional; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Irritable Bowel Syndrome; Diarrhea; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Mirtazapine
• Other Study ID Numbers: 23-011874

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No