Enteric-Coated Peppermint Oil Versus Standard Antispasmodic in SLC6A4 (5-HTTLPR) Carriers With Irritable Bowel Syndrome.

"A Non-Inferiority Randomized Controlled Trial of Enteric-Coated Peppermint Oil Versus Standard Antispasmodic in SLC6A4 (5-HTTLPR) Carriers With Irritable Bowel Syndrome."

This study is a non-inferiority, double-blind, randomized controlled trial comparing enteric-coated peppermint oil with a standard antispasmodic (e.g., mebeverine) in adult IBS patients who carry at least one "S" allele in the SLC6A4 (5-HTTLPR) polymorphism. The primary goal is to see whether peppermint oil provides symptom relief (measured by IBS severity scores) that is not worse than the antispasmodic by more than a predefined margin (30 points on the IBS-SSS). Secondary goals include evaluating differences in abdominal pain, stool patterns, quality of life, and adverse event profiles, with a focus on peppermint oil's tolerability. About 224 participants (112 per arm) will be enrolled, with allowances for dropout, to detect non-inferiority at 80% power. After 12 weeks of treatment, results will inform whether peppermint oil is a viable, well-tolerated alternative to standard antispasmodics, especially in patients with heightened GI sensitivity linked to the SLC6A4 polymorphism.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome (IBS)
• Intervention / Treatment: Dietary supplement: Peppermint Oil; Drug: A standard antispasmodic

Detailed Description

This double-blind, parallel-group, non-inferiority RCT will randomize ~250 adults (18-65 y) who meet Rome IV criteria for IBS and carry at least one short 5-HTTLPR (SLC6A4) allele to enteric-coated peppermint-oil capsules (180 mg three times daily) or the standard antispasmodic mebeverine (135 mg three times daily) for 12 weeks. Because the S-allele reduces serotonin-transporter expression and heightens visceral sensitivity, the study targets a genetically defined subgroup in which menthol's smooth-muscle-relaxing calcium-channel blockade may yield clinically meaningful benefit with fewer anticholinergic effects. Randomisation (1 : 1) is web-based, stratified by genotype and centre, and treatments are packaged identically to maintain blinding of participants, investigators, and outcome assessors. The primary endpoint is change from baseline in the IBS Severity Scoring System at week 12; non-inferiority is met if the upper bound of the two-sided 95 % CI for the treatment difference (peppermint - mebeverine) is ≤ +30 points. A mixed-model repeated-measures analysis will be applied to both intention-to-treat and per-protocol populations, providing 80 % power with ~112 evaluable patients per arm. Secondary outcomes include abdominal-pain intensity, stool form, quality of life, global satisfaction, and adverse events; safety is tracked via weekly contacts, laboratory tests, and an independent data-safety monitoring board. Demonstrating that peppermint oil is at least as effective as mebeverine while better tolerated would support its use as a genotype-guided first-line therapy for IBS.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630090
    • Center for New Medical Technologirs

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults aged 18-65 years.
• Diagnosis of Irritable Bowel Syndrome by Rome IV criteria, with at least moderate severity (IBS-SSS ≥ 175).
• SLC6A4 genotyping confirms at least one S allele (SS or SL).
• Able and willing to provide informed consent and comply with study procedures.

Exclusion Criteria:

• L/L genotype of 5-HTTLPR.
• Known organic GI diseases (e.g., IBD, celiac disease).
• Severe/unstable comorbidities (e.g., cardiac, hepatic, or renal dysfunction).
• Use of peppermint oil, antispasmodics, or investigational drugs within 30 days prior to enrollment.
• . Known hypersensitivity to peppermint or mebeverine.
• Pregnancy or breastfeeding.
• Significant psychiatric illness that, in the investigator's judgment, might interfere with participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Enteric-coated peppermint oil capsules (~180 mg total peppermint oil/ capsule) to ensure release in	Dietary supplement: Peppermint Oil; Enteric-coated peppermint oil capsules (~180 mg total peppermint oil/ capsule) to ensure release in the small intestine. 1 capsule three times daily, 30 minutes before meals, for 12 weeks.
Active Comparator: A standard antispasmodiс; A standard antispasmodic (e.g., mebeverine 135 mg).	Drug: A standard antispasmodic; A standard antispasmodic (e.g., mebeverine 135 mg). 1 tablet three times daily, before meals, for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Irritable Bowel Syndrome	Symptom severity in this trial is captured with the IBS-SSS (IBS Severity Scoring System): 0 = no symptoms to 500 = most severe symptoms	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events: Incidence	Number of any adverse events	12 weeks
Numeric Rating Scale (for abdominal pain)	Range: 0 = no pain to 10 = worst imaginable pain	12 weeks
Abdominal Pain: Measured by visual analog score	0 as a minimum value and 10 maximum value	12 weeks
Stool Consistency: Bristol Stool Form Scale	range 1-7, 1 = separate hard lumps/constipation, 7 = watery stool/diarrhea; higher scores indicate looser stool	12 weeks
Quality of Life: Irritable Bowel Syndrome Quality of Life Questionnaire	transformed score 0-100; higher scores indicate better IBS-specific quality of life	12 weeks
Quality of Life: 36-Item Short Form Health Survey	domain and summary scores 0-100; higher scores indicate better health-related quality of life	12 weeks
Global Patient Satisfaction: Five-point Likert Scale	ange 1-5 (1 = very dissatisfied, 5 = very satisfied); higher scores indicate greater satisfaction	12 weeks

Collaborators and Investigators

• Sponsor: S.LAB (SOLOWAYS)
• Collaborators: Center for New Medical Technologies, Novosibirsk, Russia

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2024
• Primary Completion (Actual): January 17, 2025
• Study Completion (Actual): February 1, 2025

Study Registration Dates

• First Submitted: April 4, 2025
• First Submitted That Met QC Criteria: April 4, 2025
• First Posted (Actual): April 7, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: genetics; supplements; peppermint oil
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Disease; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Colonic Diseases, Functional; Irritable Bowel Syndrome; Syndrome; Physiological Effects of Drugs; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Parasympatholytics; Peppermint oil
• Other Study ID Numbers: SW027

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