Mirtazapine + Low-FODMAP Diet for IBS

Overseen By Wendi M Lehman

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Disqualifiers: Celiac disease, IBD, Anxiety, others

Compensation: Varies

Number of Visits: 3

Duration: 7 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well mirtazapine, an antidepressant, works with a low-FODMAP diet to relieve symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D). The trial compares this combination treatment to the low-FODMAP diet alone. Participants will receive either mirtazapine or a placebo (a pill with no active medication) to determine any added benefit. Individuals with IBS-D symptoms who have not improved with diet changes alone may be suitable for this study. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have shown that mirtazapine helps with IBS symptoms, such as stool consistency and abdominal pain. While these results are promising, considering the safety of mirtazapine is important. Most people tolerate the treatment well, but it can cause side effects. Some individuals might experience drowsiness or weight gain. More serious side effects, like serotonin syndrome, can occur if mirtazapine is taken with certain other medications. Notably, mirtazapine is already approved for other uses, such as treating depression, which provides some insight into its safety. However, since this trial is in the early stages, the full safety details specifically for IBS treatment are still under study. Always discuss any concerns with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for IBS?

Researchers are excited about using mirtazapine for irritable bowel syndrome (IBS) because it represents a novel approach compared to existing treatments, which often include antispasmodics, laxatives, and dietary changes. Mirtazapine, an antidepressant, works by modulating serotonin and norepinephrine in the brain, which may help address the brain-gut interaction believed to play a role in IBS symptoms. This new mechanism of action could offer relief for patients who haven't benefited from traditional IBS therapies, potentially reducing both the emotional and physical symptoms of the condition.

What evidence suggests that mirtazapine combined with a low-FODMAP diet might be an effective treatment for IBS?

Research has shown that mirtazapine, which participants in this trial may receive, can help reduce symptoms of irritable bowel syndrome (IBS), particularly when diarrhea is the main issue. One study found that mirtazapine significantly lessened IBS symptoms compared to a placebo, with a clear drop in symptom severity scores. Another report described a case where mirtazapine helped a patient with IBS. Additionally, a review of several studies has shown that antidepressants, like mirtazapine, improve overall symptoms in IBS patients. These findings suggest that mirtazapine might be a useful addition to a low-FODMAP diet for managing IBS symptoms. ^{3 6 7 8 9}

Who Is on the Research Team?

Brian E Lacy, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults aged 18-70 with diarrhea-predominant irritable bowel syndrome (IBS-D) who meet specific IBS criteria and have a significant symptom score can join. They must understand the study, follow its procedures, and not be pregnant if capable of reproduction.

Inclusion Criteria

Participants must have a score of greater than 175 on the IBS-SSS questionnaire

I can understand and follow the study's procedures.

If subject is of reproductive capability, a negative urine pregnancy test must be available prior to entering the study

Exclusion Criteria

Participants with a score of less than 175 on the IBS-SSS

I have been diagnosed with celiac, IBD, SIBO, or microscopic colitis.

Participants with a history of a known side effect to mirtazapine

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either mirtazapine or placebo in combination with a low-FODMAP diet

7 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirtazapine

Trial Overview

The trial is testing whether adding mirtazapine to a low-FODMAP diet provides more relief for IBS symptoms than the diet alone. Participants will either receive mirtazapine or a placebo while following the dietary restrictions.

How Is the Trial Designed?

Group I: Mirtazapine Group Experimental Treatment 1 Intervention

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.

Group II: Placebo Group Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

A systematic review of nine randomized controlled trials involving 542 patients found that the low FODMAP diet for irritable bowel syndrome (IBS) has a high risk of bias, particularly in blinding, with only one trial being double-blinded.

The studies generally lasted from 2 days to 6 weeks, and there is a lack of research on the long-term effects and the important reintroduction phase of the diet, raising concerns that reported symptom improvements may be largely due to placebo effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review: quality of trials on the symptomatic effects of the low FODMAP diet for irritable bowel syndrome. Krogsgaard, LR., Lyngesen, M., Bytzer, P.[2022]

The low FODMAP diet has gained attention as a dietary treatment for irritable bowel syndrome (IBS), showing increasing clinical evidence for its efficacy in managing symptoms.

While the diet appears effective, there are still significant concerns regarding its short- and long-term safety, as well as its impact on gut microbiota and overall nutrition that need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low FODMAP in 2017: Lessons learned from clinical trials and mechanistic studies. Eswaran, S.[2018]

A low FODMAP diet significantly improved symptoms in 90 IBS patients over an average follow-up of 15.7 months, with reductions in abdominal pain, bloating, flatulence, and diarrhea (p < 0.001 for all).

Patients with fructose malabsorption showed the greatest symptom improvement, and adherence to the low FODMAP diet was high (75.6%), correlating with better outcomes and satisfaction in 72.1% of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The low FODMAP diet improves gastrointestinal symptoms in patients with irritable bowel syndrome: a prospective study. de Roest, RH., Dobbs, BR., Chapman, BA., et al.[2022]

The low FODMAP diet has been shown to improve symptoms of irritable bowel syndrome (IBS) by reducing the intake of short-chain fermentable carbohydrates that can trigger gastrointestinal discomfort.

While there is growing clinical evidence supporting the effectiveness of the low FODMAP diet for IBS, it is important to consider potential drawbacks and to implement the diet carefully under professional guidance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutrition in the management of gastrointestinal diseases and disorders: the evidence for the low FODMAP diet. Eswaran, S., Farida, JP., Green, J., et al.[2018]

After 12 months on a personalized low FODMAP diet, 67% of participants with irritable bowel syndrome (IBS) reported adequate relief of symptoms, a significant increase from 28% at baseline.

While the diet improved symptoms, it did not significantly change the abundance of Bifidobacteria in the gut microbiota, although there was a noted decrease in short-chain fatty acids (SCFAs), suggesting that long-term dietary changes may normalize some effects of initial FODMAP restriction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term personalized low FODMAP diet improves symptoms and maintains luminal Bifidobacteria abundance in irritable bowel syndrome. Staudacher, HM., Rossi, M., Kaminski, T., et al.[2022]

The low-FODMAP diet can help alleviate symptoms of irritable bowel syndrome (IBS), such as bloating and diarrhea, but the evidence supporting its effectiveness is limited due to methodological flaws in studies, including a lack of proper control groups.

Prolonged use of the low-FODMAP diet may lead to nutritional deficiencies because it restricts many staple foods, potentially resulting in lower intake of essential nutrients like fiber, calcium, and vitamins, especially for those with limited access to alternative foods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Low FODMAP Diet: Many Question Marks for a Catchy Acronym. Catassi, G., Lionetti, E., Gatti, S., et al.[2022]

A low-FODMAP diet has been shown to significantly improve IBS symptoms in 52-86% of patients, making it a highly effective dietary intervention for this condition.

Patients who benefit from eliminating FODMAPs should follow a structured reintroduction process to identify specific food sensitivities, allowing for a personalized diet plan tailored to their needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-FODMAP Diet for Irritable Bowel Syndrome: What We Know and What We Have Yet to Learn. Liu, J., Chey, WD., Haller, E., et al.[2020]

In a study of 233 IBS patients, 41% adhered to a low-FODMAP diet, and higher adherence was linked to a greater risk of eating disorder (ED) behaviors, with 23% of participants identified as at risk for EDs.

Patients with IBS who adhered to the low-FODMAP diet showed a significant difference in adherence rates between those at risk for EDs (57%) and those not at risk (35%), highlighting the need for clinicians to monitor for EDs in patients with high adherence to this restrictive diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence with a low-FODMAP diet in irritable bowel syndrome: are eating disorders the missing link? Mari, A., Hosadurg, D., Martin, L., et al.[2019]

A low FODMAP diet significantly reduces abdominal pain in children with irritable bowel syndrome (IBS), with participants experiencing fewer pain episodes compared to a typical American childhood diet, as shown in a study involving 33 children.

The study suggests that certain gut microbiome characteristics, particularly those related to carbohydrate metabolism, may predict which children will respond positively to the low FODMAP diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome. Chumpitazi, BP., Cope, JL., Hollister, EB., et al.[2022]

The low FODMAP diet is the most evidence-supported dietary intervention for treating irritable bowel syndrome (IBS), which affects 10% to 15% of the population.

While dietary therapies are becoming first-line treatments for IBS, healthcare providers must be cautious of the potential negative effects of restrictive diets and be vigilant for signs of maladaptive eating patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irritable Bowel Syndrome: Food as a Friend or Foe? Harer, KN., Eswaran, SL.[2021]

In a study of 459 primary care patients with IBS, a smartphone application promoting a low FODMAP diet resulted in a significantly higher symptom improvement rate (71%) compared to the spasmolytic agent otilonium bromide (61%) after 8 weeks.

The FODMAP diet not only showed better efficacy but also higher adherence rates (94% for diet vs. 73% for OB), suggesting it could be a more effective first-line treatment for IBS in primary care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute. Carbone, F., Van den Houte, K., Besard, L., et al.[2023]

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