Varenicline for Irritable Bowel Syndrome

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Antidepressants, Pain medications, CYP3A4 drugs

Disqualifiers: Depression, Substance abuse, Seizure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 8 days

8 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the medication varenicline can help individuals with irritable bowel syndrome (IBS) who experience chronic abdominal pain without constipation. The goal is to determine if varenicline can alter the body's perception of gut pain. Suitable participants have IBS with diarrhea or mixed symptoms and experience regular abdominal pain. This trial does not include individuals with depression, recent substance issues, or serious liver or kidney problems. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you've had a significant change in antidepressant or pain medications in the last four weeks, or if you are using strong CYP3A4 inhibitors or inducers.

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

Research has shown that varenicline, also known as Chantix, is generally safe for adults. The FDA has approved it to help people quit smoking. Common side effects include stomach issues such as nausea, constipation, and gas. Some individuals also experience unusual dreams and mood changes.

Studies with various groups found varenicline to be safe, though unwanted effects were common. This suggests that while varenicline is usually well-tolerated, some individuals may experience side effects. It is important to consult a healthcare provider about what to expect and whether this treatment is suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for Irritable Bowel Syndrome (IBS) focus on managing symptoms through dietary changes, fiber supplements, antispasmodics, or medications like loperamide for diarrhea and laxatives for constipation. But Varenicline offers a fresh approach by targeting nicotinic acetylcholine receptors, specifically as a partial agonist at α4β2 and α6β2 receptors. This unique mechanism might not only help with IBS symptoms but also address chronic pain, which is often a challenging aspect of IBS that current treatments don't directly target. Researchers are excited about Varenicline because it could offer a new way to manage IBS, especially for those who haven't found relief with existing therapies.

What evidence suggests that varenicline might be an effective treatment for IBS?

Research has shown that varenicline, a medication primarily used to help people quit smoking, might also influence gut sensations. Animal studies found that varenicline can reduce activity in the colon, potentially alleviating symptoms for those with irritable bowel syndrome (IBS). Varenicline partially activates certain receptors in the brain and gut, affecting pain and discomfort. Although using varenicline for IBS is still in the early stages, these findings suggest it might help reduce abdominal pain and discomfort. Further research is necessary to determine its effectiveness for IBS. Participants in this trial will receive varenicline to assess its potential benefits for IBS. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael Camilleri

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

Adults aged 18-70 with Irritable Bowel Syndrome (IBS) that includes pain but not constipation can join this study. They shouldn't have a recent history of substance abuse, be pregnant or unstable medically, and should not have had changes in antidepressant or pain medications recently.

Inclusion Criteria

I have IBS with pain but no constipation.

Exclusion Criteria

Alcohol or illicit substance dependence or abuse in the past 12 months

Pregnancy (all women of childbearing potential will be required to have a negative pregnancy test prior to initiation, and will be on a highly effective method of contraception, as detailed in the consent form)

Medically unstable

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive varenicline to evaluate its effect on rectal sensation

8 days

1 visit (in-person) on day 8

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Varenicline

Trial Overview The trial is testing Varenicline to see if it affects how people with IBS feel pain in their gut. Participants will undergo tests where their rectal sensation is measured after taking the medication.

How Is the Trial Designed?

Group I: Varenicicline Experimental Treatment 1 Intervention

Varenicline is a α4β2 and α6β2 partial agonist. Varenicline (Chantix) is an FDA-approved partial agonist at α4β2 and α6β2 nAChRs with documented efficacy in the management of chronic pain associated with opioid withdrawal

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Varenicline, a medication designed to help people quit smoking, can cause gastrointestinal side effects, including rare cases of functional adynamic ileus, as seen in a 75-year-old man.

Healthcare providers should be aware of this potential side effect, as it may lead to the discontinuation of varenicline and require a reassessment of the patient's smoking cessation plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adynamic ileus induced by varenicline. Vasco, PG., López, AR.[2019]

Varenicline is an effective treatment for nicotine addiction, promoting abstinence safely in most patients, but there are reports of neuropsychiatric adverse events in a small number of cases.

Veterans, who often have higher rates of psychiatric conditions and nicotine dependence, may be at increased risk for serious side effects from varenicline, highlighting the need for close monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse neuropsychiatric events associated with varenicline use in veterans: a case series. Cantrell, M., Argo, T., Haak, L., et al.[2015]

Mebeverine has been shown to significantly reduce abdominal pain in patients with irritable bowel syndrome (IBS), with 6 out of 22 studies reporting strong positive results.

The treatment also improved other IBS symptoms such as abnormal bowel habits and abdominal distension, while demonstrating a good safety profile with rare adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Mebeverine in the Treatment of Irritable Bowel Syndrome-A Systematic Review. Daniluk, J., Malecka-Wojciesko, E., Skrzydlo-Radomanska, B., et al.[2022]

In a large trial involving 463 participants, low-dose amitriptyline (10-30 mg) was found to be significantly more effective than placebo in reducing IBS symptoms after 6 months, with a notable improvement in the IBS Severity Scoring System (IBS-SSS) score.

The study demonstrated that low-dose amitriptyline was safe and well tolerated, with a similar rate of discontinuation due to adverse events compared to placebo, suggesting it can be a viable second-line treatment for IBS in primary care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Ford, AC., Wright-Hughes, A., Alderson, SL., et al.[2023]

A case report of a 53-year-old woman with Type 1 diabetes revealed multiple episodes of severe hypoglycaemia after starting varenicline, a drug typically used for smoking cessation, which had not been previously associated with this side effect.

The hypoglycaemic episodes ceased after discontinuing varenicline, suggesting that healthcare providers should exercise caution when prescribing this medication to patients with diabetes and recommend close monitoring of blood glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline may trigger severe hypoglycaemia in Type 1 diabetes. Kristensen, PL., Pedersen-Bjergaard, U., Thorsteinsson, B.[2015]

A case series identified 30 reports of haemorrhagic events, including epistaxis and gingival bleeding, associated with varenicline, suggesting a potential causal relationship, especially since some patients improved after stopping the medication.

The proposed mechanism for these bleeding events may involve interactions with the serotonin receptor system, indicating a need for further investigation into the safety profile of varenicline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epistaxis and other haemorrhagic events associated with the smoking cessation medicine varenicline: a case series from two national pharmacovigilance centres. Harrison-Woolrych, M., Härmark, L., Tan, M., et al.[2021]

In a pilot study of 20 patients with irritable bowel syndrome (IBS) treated with paroxetine for 12 weeks, 65% reported a reduction in abdominal pain, indicating its potential efficacy in managing IBS symptoms.

Paroxetine also significantly reduced constipation and diarrhea in 69% and 57% of patients, respectively, suggesting it may help alleviate multiple symptoms associated with IBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paroxetine in Patients With Irritable Bowel Syndrome: A Pilot Open-Label Study. Masand, PS., Gupta, S., Schwartz, TL., et al.[2020]

Mirtazapine, a potent 5-HT3 receptor antagonist, was effective in treating a 66-year-old woman with mixed-type irritable bowel syndrome (IBS), leading to improvements in both her gastrointestinal symptoms and psychological conditions.

Unlike alosetron, which was withdrawn from the market due to serious side effects, mirtazapine appears to provide a safer alternative for managing IBS symptoms, particularly in patients with coexisting psychological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of irritable bowel syndrome with comorbid anxiety symptoms with mirtazapine. Spiegel, DR., Kolb, R.[2018]

Buspirone, a 5-HT1A agonist, shows promise in improving symptoms of functional dyspepsia by enhancing gastric accommodation and reducing discomfort after meals.

While some antidepressants like venlafaxine and tricyclics can affect gut function, their side effects and limited efficacy in certain populations highlight the need for larger, more targeted clinical trials to better understand their role in treating gastrointestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects on gastrointestinal functions and symptoms of serotonergic psychoactive agents used in functional gastrointestinal diseases. Grover, M., Camilleri, M.[2022]

Varenicline is an effective smoking cessation aid, but its safety is questionable for patients with mental illnesses due to potential neuropsychiatric side effects.

Two case studies of patients with bipolar disorder showed that varenicline can trigger manic symptoms, highlighting the risks of prescribing this medication to individuals with severe mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypomania following the use of varenicline in two patients with bipolar disorder]. Sluys, ML., Remmers, A., Beerthuis, RJ.[2015]

Citations

1. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/579865

A Study of Varenicline in the Treatment of Visceral Sensation The purpose of this study is to evaluate the effect of varenicline on rectal sensation, based on ascending method of limits and on graded ...

2. withpower.com withpower.com/trial/phase-1-irritable-bowel-syndrome-3-2025-c523e

Varenicline for Irritable Bowel Syndrome Mebeverine has been shown to significantly reduce abdominal pain in patients with irritable bowel syndrome (IBS), with 6 out of 22 studies reporting strong ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3548414/

A Novel Approach to the Symptomatic Treatment of IBS-D - PMC For example, alosetron displays efficacy in the treatment of multiple symptoms, including abdominal pain, discomfort, urgency, stool frequency and consistency.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524465695

Varenicline Is a Potent Agonist of the Human 5- ... Alosetron is an effective symptomatic treatment for irritable bowel syndrome. In addition, studies have revealed a diversity of potential disease targets ...

5. alliedacademies.org alliedacademies.org/articles/effect-of-varenicline-on-colonic-motility-in-a-rat-model-of-experimental-irritable-bowel.html

Effect of varenicline on colonic motility in a rat model ... Varenicline significantly decreased the mean pressure values of distal colon according to initial spontaneous colonic activity in both control and IBS rats.

6. mayoclinic.org mayoclinic.org/drugs-supplements/varenicline-oral-route/description/drg-20068324

Varenicline (oral route) - Side effects & dosage Use is not recommended in children 16 years of age and younger. Safety and efficacy have not been established.

7. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9PFIZ_69047102_CHANTIX_TABLETS.pdf

SAFETY DATA SHEET This document has been prepared in accordance with standards for workplace safety, which requires the inclusion of all known hazards of the product or its ...

8. goodrx.com goodrx.com/varenicline/chantix-side-effects?srsltid=AfmBOor10LIfpAh4De9LImsLmUUgggECPH_k-U4qa_SaFW9V2oLFAddU

Common Chantix Side Effects Everyone Should Know Common Chantix side effects include stomach-related symptoms like nausea, constipation, and gas. Abnormal dreams and mood changes are also possible. Chantix can ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3242617/

Safety and Tolerability of Varenicline Tartrate (Champix®/ ... Varenicline was safe and appears effective among HIV-infected smokers in this exploratory study, although AEs were common.

10. pfe-pfizercom-prod.s3.amazonaws.com pfe-pfizercom-prod.s3.amazonaws.com/products/material_safety_data/varenicline_tartrate_tablets-13-may-2016.pdf

SAFETY DATA SHEET This document has been prepared in accordance with standards for workplace safety, which requires the inclusion of all known hazards of the ...