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

Trial Summary

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 varenicline safe for humans?

Varenicline, a drug used to help people stop smoking, can cause side effects like nausea, vomiting, and constipation. It may also lead to rare conditions like adynamic ileus (a type of bowel blockage) and has been linked to neuropsychiatric issues, especially in people with mental health conditions. Some reports suggest it might trigger severe low blood sugar in people with Type 1 diabetes and cause bleeding events. ^{1 2 3 4 5}

How does the drug Varenicline differ from other treatments for irritable bowel syndrome?

Varenicline is unique for IBS treatment as it is primarily known for helping people quit smoking by targeting nicotine receptors in the brain, which is different from other IBS treatments that often focus on serotonin or gut motility. This novel approach may offer a new mechanism of action for managing IBS symptoms. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this study is to evaluate the effect of varenicline on rectal sensation, based on ascending method of limits and on graded rapid phasic distensions in participants with non-constipation IBS and chronic abdominal pain.

Research Team

Michael Camilleri

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Adynamic ileus induced by varenicline. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Adverse neuropsychiatric events associated with varenicline use in veterans: a case series. [2015]

3. Netherlands pubmed.ncbi.nlm.nih.gov

[Hypomania following the use of varenicline in two patients with bipolar disorder]. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Varenicline may trigger severe hypoglycaemia in Type 1 diabetes. [2015]

5. Germany 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Paroxetine in Patients With Irritable Bowel Syndrome: A Pilot Open-Label Study. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Treatment of irritable bowel syndrome with comorbid anxiety symptoms with mirtazapine. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

The Efficacy of Mebeverine in the Treatment of Irritable Bowel Syndrome-A Systematic Review. [2022]

10. England 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. [2023]