Quality of Life in Diarrhea-predominant Irritable Bowel Syndrome Taking GABA

Evaluation of Quality of Life in a Cohort of Diarrhoeic Irritable Bowel Syndrome (IBS-D) Patients Assuming GABA.

The study aims to evaluate the impact on quality of life and abdominal discomfort of GABA and Melissa food supplement administration in patients with diarrhea-predominant irritable bowel syndrome.

Study Overview

• Status: Completed
• Conditions: Diarrhoea Predominant Irritable Bowel Syndrome
• Intervention / Treatment: Other: Placebo; Other: GABA

Detailed Description

Rationale: Visceral pain represents a grievous form of pain that affects about 25% of the world population; abdominal pain is the most common gastrointestinal problem, encountered in a high percentage of adolescents, above all in women. It can be the result of prolonged inflammatory processes, such as in inflammatory bowel diseases (IBDs), but in many patients, negative diagnostic test results lead to the diagnosis of irritable bowel syndrome (IBS) .

Abdominal pain is a common manifestation in IBD, due to changes that begin with hypersensitivity of the primary sensory neurons, which innervate the gastrointestinal tract, and afterwards reach the central nervous system (CNS) . Inflammation does not seem to completely explain altered perception of pain in patients affect by IBD, as 20%-50% of patients complain about abdominal pain in the clinical remission stage . IBS is a functional bowel disorder characterized by the presence of chronic/recurrent abdominal pain or discomfort, with altered bowel habits and consequent anomalies in stool frequency and form . Pathogenesis of IBS is only partially understood, even though there is some evidence that changes in the digestive motility and secretion, visceral hypersensitivity, abnormalities of enteroendocrine and immune systems, genetic factors, infections, alterations of the intestinal microbiota and inflammation could play a role in this functional disease. . Patients may be categorized as diarrheal-predominant (IBS-D), constipation-predominant IBS-C), or as having both (IBS-M) . In this context, finding valid therapies that can alleviate chronic visceral pain represents an important medical need to improve patients' quality of life. Unfortunately, the current therapeutics to treat visceral pain offer little benefit for abdominal symptoms and can produce undesired and serious side effects . In this regard, the pain management remains unsatisfactory, so there is a growing demand for the development of effective treatments. Considering that visceral pain has been related to inflammatory processes , as well as to alterations in the enteric barrier and immune response , a product able to protect the intestinal mucosa by indirectly controlling inflammation and at the same time modulating immune response could be the answer. In this regard, gamma aminobutyric acid (GABA) is known to exert a number of beneficial effects at digestive level. For instance, GABA has a protective role during inflammatory processes by modulating cytokine production . Moreover, products containing GABA have been proven to strengthen intestinal epithelial barrier and to modulate immune-inflammatory response .

Objectives: Primary: to evaluate the changes in quality of life in IBS-D patients taking GABA food supplement. Secondary: evaluation of changes in abdominal discomfort in IBS-D patients taking GABA food supplement; evaluation of global symptom score in IBS-D patients taking GABA food supplement; self evaluation of psychological impact of IBS-D in patients taking GABA food supplement; intestinal microbiota changes in IBS-D patients taking GABA food supplement; evaluation of epithelial barrier impairment in IBS-D patients taking GABA food supplement; evaluation of systemic inflammation in IBS-D patients taking GABA food supplement.

Investigational product, dose, and mode of administration: Regimen A: EIRENE® (containing GABA and Melissa officials) food supplement table 530 mg, 1 tablet three times a day. Regimen B: placebo (microcrystalline cellulose, rice bran, bitter cocoa powder) table 530 mg, 1 tablet three times a day.

Methodology: This is a monocentric, randomized, double-blind, parallel group, placebo-controlled, 2-period cross-over study investigating the changes in quality of life, abdominal symptoms, intestinal microbiota, intestinal permeability, systemic inflammation in patients taking a GABA-based food supplement. Patients will be evaluated before and after each treatment period (Regimen A and Regimen B) through clinical questionnaires and scales, blood and stool tests.

The following questionnaires will be administered:

• Short-Form 36
• 11 points visual analogue scale for abdominal discomfort
• Hospital Anxiety and Depression Scale
• Bristol Stool Scale

The following evaluations will be performed on blood samples:

• TNF-alfa, IL-1β, C-reactive protein and IL-10 levels to assess systemic inflammation
• Lypopolisaccharide binding protein (LBP) to assess intestinal epithelial barrier impairment.
• Blood tests for safety (glucose, BUN, AST, ALT, bilirubin, ALP, creatinin, blood count and formula, platelets, Na, K, Ca)

The following evaluations will be performed on stool samples:

• Fecal calprotectin
• Fecal microbiome analysis

Inclusion criteria: Age > 18 years and ≤ 75; a positive diagnosis of IBS-D according to Rome IV criteria; both males and females; negative relevant additional screening or consultation whenever appropriate; colonoscopy if there are alarm symptoms (eg. Rectal bleeding, pseudodiarrhea. If the patients' age is > or = 50 yrs a colonoscopy within 5 years is mandatory); availability to participate in the clinical study, confirmed by the signed informed consent form; ability to conform to the study protocol; patients' ability to complain study protocol procedures; subjects who decide to use single or double contraceptive methods not to conceive during study period.

Exclusion criteria: patients with IBS-C, IBS-M and IBS-U according to Rome IV criteria; presence of any relevant organic, systemic or metabolic disease (particularly significant history of cardiac, renal, neurological, psychiatric, oncology, endocrinology, metabolic or hepatic disease), or abnormal laboratory values that will be deemed clinically significant; ascertained intestinal organic diseases, including celiac disease, food allergies or inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticular disease, infectious colitis, ischemic colitis, microscopic colitis); previous major abdominal surgery; active malignancy of any type, or history of a malignancy (patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before study enrollment are also acceptable); use of -pre or probiotics, topical and/or systemic antibiotic and prokinetic therapy during the 15 days before treatment starts; systematic/frequent use of contact laxatives; pregnant or breastfeeding woman; females of childbearing potential in the absence of effective contraceptive methods; inability to conform to protocol; treatment with any investigational drug within the previous 30 days; recent history or suspicion of alcohol abuse or drug addiction; presence of red or white flags at the Rome IV Psychosocial Alarm Questionnaire for Functional gastrointestinal Disorders.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Pisa, Italy, 56124
    • Azienda Ospedaliero Universitaria Pisana
  • Pisa, Italy, 56126
    • University of Pisa

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age > 18 years and ≤ 75
• A positive diagnosis of IBS-D according to Rome IV criteria.
• Both males and females.
• Negative relevant additional screening or consultation whenever appropriate
• Colonoscopy if there are alarm symptoms (eg. Rectal bleeding, pseudodiarrhea). If the patients' age is > or = 50 yrs a colonoscopy within 5 years is mandatory.
• Availability to participate in the clinical study, confirmed by the signed informed consent form.
• Ability to conform to the study protocol.
• Patients' ability to complain study protocol procedures.
• Subjects who decide to use single or double contraceptive methods not to conceive during study period.

Exclusion Criteria:

• Patients with IBS-C, IBS-M and IBS-U according to Rome IV criteria.
• Presence of any relevant organic, systemic or metabolic disease (particularly significant history of cardiac, renal, neurological, psychiatric, oncology, endocrinology, metabolic or hepatic disease), or abnormal laboratory values that will be deemed clinically significant.
• Ascertained intestinal organic diseases, including celiac disease, food allergies or inflammatory bowel diseases (Crohn's disease, ulcerative colitis, diverticular disease, infectious colitis, ischemic colitis, microscopic colitis).
• Previous major abdominal surgery.
• Active malignancy of any type, or history of a malignancy (patients with a history of other malignancies that have been surgically removed and who have no evidence of recurrence for at least five years before study enrolment are also acceptable).
• Use of -pre or probiotics, topical and/or systemic antibiotic and prokinetic therapy during the 15 days before treatment starts.
• Systematic/frequent use of contact laxatives.
• Pregnant or breastfeeding woman.
• Females of childbearing potential in the absence of effective contraceptive methods.
• Inability to conform to protocol.
• Treatment with any investigational drug within the previous 30 days.
• Recent history or suspicion of alcohol abuse or drug addiction.
• Presence of red or white flags at the Rome IV Psychosocial Alarm Questionnaire for Functional gastrointestinal Disorders

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A	Other: Placebo; 530 mg tablets containing microcrystalline cellulose, rice bran, bitter cocoa powder table 530 mg. 1 tablet three times a day; Other: GABA; 530 mg tablets containing Gamma-aminobutyric acid (GABA) and different bulking agent as microcrystalline cellulose, calcium carbonate, lemon balm d.e. Leaves (melissa officinalis l. - maltodextrin) tit. 2% in rosmarinic acid, anti-caking agents: silicon dioxide, vegetable magnesium stearate. 1 tablet three times a day
Experimental: Group B	Other: Placebo; 530 mg tablets containing microcrystalline cellulose, rice bran, bitter cocoa powder table 530 mg. 1 tablet three times a day; Other: GABA; 530 mg tablets containing Gamma-aminobutyric acid (GABA) and different bulking agent as microcrystalline cellulose, calcium carbonate, lemon balm d.e. Leaves (melissa officinalis l. - maltodextrin) tit. 2% in rosmarinic acid, anti-caking agents: silicon dioxide, vegetable magnesium stearate. 1 tablet three times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	Evaluation of quality of life in IBS-D patients taking GABA food supplement with Short-Form 36 Items Health Survey (SF-36 Italian version). A reduction at least of 10 points on at least 1 of the 8 subdomains of the SF36 score would be considered significant.	From enrollment to the end of treatment at 12 weeks. Evaluated at every scheduled visit (V0, V1, V2, V3, FU)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychological impact	Self evaluation of psychological impact of IBS-D in patients taking GABA food supplement with Hospital Anxiety and Depression Scale (HADS).	From enrollment to the end of treatment at 12 weeks. Evaluated at every scheduled visit (V0, V1, V2, V3, FU)
Intestinal microbiota	Microbiota changes in IBS-D patients taking GABA food supplement with NGS analysis. Results will be evaluated describing variations of principal genera and family variation.	From enrollment to the end of treatment at 10 weeks. Evaluated at every scheduled visit (V0, V1, V2, V3)
Epithelial barrier impairment	Evaluation of epithelial barrier impairment in IBS-D patients taking GABA food supplement with haematological dosage of Lypopolisaccharide binding protein (LBP).	From enrollment to the end of treatment at 10 weeks. Evaluated at every scheduled visit (V0, V1, V2, V3)
Systemic inflammation	Evaluation of systemic inflammation in IBS-D patients taking GABA food supplement with haematological dosage of TNF-alfa, IL-1β, C-reactive protein and IL-10 levels	From enrollment to the end of treatment at 10 weeks. Evaluated at every scheduled visit (V0, V1, V2, V3)
Abdominal discomfort	Abdominal discomfort evaluated by a 11 points visual analogue scale	From enrollment to the end of treatment at 12 weeks. Evaluated at every scheduled visit (V0 (Week0), V1(Week 4), V2(Week 6), V3(week 10), FU(Week 12))

Collaborators and Investigators

• Sponsor: University of Pisa
• Collaborators: Azienda Ospedaliero-Universitaria Pisana (AOUP)

Publications and helpful links

General Publications

• Minderhoud IM, Oldenburg B, Wismeijer JA, van Berge Henegouwen GP, Smout AJ. IBS-like symptoms in patients with inflammatory bowel disease in remission; relationships with quality of life and coping behavior. Dig Dis Sci. 2004 Mar;49(3):469-74. doi: 10.1023/b:ddas.0000020506.84248.f9.
• Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel Disorders. Gastroenterology. 2016 Feb 18:S0016-5085(16)00222-5. doi: 10.1053/j.gastro.2016.02.031. Online ahead of print.
• Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015 Apr-Jun;28(2):203-209.
• Sokovic Bajic S, Djokic J, Dinic M, Veljovic K, Golic N, Mihajlovic S, Tolinacki M. GABA-Producing Natural Dairy Isolate From Artisanal Zlatar Cheese Attenuates Gut Inflammation and Strengthens Gut Epithelial Barrier in vitro. Front Microbiol. 2019 Mar 18;10:527. doi: 10.3389/fmicb.2019.00527. eCollection 2019.
• Gros M, Gros B, Mesonero JE, Latorre E. Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management. J Clin Med. 2021 Jul 31;10(15):3429. doi: 10.3390/jcm10153429.
• Cervero F. Central sensitization and visceral hypersensitivity: Facts and fictions. Scand J Pain. 2014 Apr 1;5(2):49-50. doi: 10.1016/j.sjpain.2014.02.005. No abstract available.
• Bellini M, Gambaccini D, Stasi C, Urbano MT, Marchi S, Usai-Satta P. Irritable bowel syndrome: a disease still searching for pathogenesis, diagnosis and therapy. World J Gastroenterol. 2014 Jul 21;20(27):8807-20. doi: 10.3748/wjg.v20.i27.8807.
• Portincasa P, Bonfrate L, de Bari O, Lembo A, Ballou S. Irritable bowel syndrome and diet. Gastroenterol Rep (Oxf). 2017 Feb;5(1):11-19. doi: 10.1093/gastro/gow047. Epub 2017 Jan 20.
• Morales-Soto W, Gulbransen BD. Enteric Glia: A New Player in Abdominal Pain. Cell Mol Gastroenterol Hepatol. 2019;7(2):433-445. doi: 10.1016/j.jcmgh.2018.11.005. Epub 2018 Nov 24.

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Actual): November 19, 2024
• Study Completion (Actual): March 21, 2025

Study Registration Dates

• First Submitted: December 23, 2024
• First Submitted That Met QC Criteria: December 23, 2024
• First Posted (Actual): January 1, 2025

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: February 3, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: diarrhoea; abdominal pain; irritable bowel syndrome; GABA; gamma-aminobutyric acid
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; 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; Abdominal Pain; Diarrhea; Amino Acids, Peptides, and Proteins; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amino Acids; Aminobutyrates; Butyrates; gamma-Aminobutyric Acid
• Other Study ID Numbers: GABA 2.0

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