## Protocol Section
### Identification Module
**NCT ID:** NCT06432569

**Acronym:** B/P3_1

**Brief Title:** Evaluation of Butyrate and Palmitoylethanolamide in IBS Patients (B/P3_1)

**Official Title:** Evaluation of Butyrate and Palmitoylethanolamide Effects on Intestinal Permeability and Microbiota Gut Composition in Patients With Irritable Bowel Syndrome - A Double-blind, Placebo-controlled Crossover Randomized Study

#### Organization Study ID Info
**ID:** 5475-AO-22
#### Organization
**Class:** OTHER
**Full Name:** University of Padova
### Status Module
#### Completion Date
**Date:** 2025-12-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-29

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2025-03-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03-08

**Type:** ACTUAL

**Status Verified Date:** 2024-03

#### Study First Post Date
**Date:** 2024-05-29
**Type:** ACTUAL
**Study First Submit Date:** 2023-02-27
**Study First Submit QC Date:** 2024-05-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Padova

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Evaluation of the effects of butyrate ( BitirBioma) and palmitoylethanolamide( PEA=PeaBioma) on intestinal permeability and gut microbiota composition in patients with irritable bowel syndrome.

Study B/P 3_1 is an interventional study involving the use of food supplements on the market (BitirBioma Plus and PeaBioma Plus), single-center, double-blind, placebo-controlled, crossover, randomized, in n=50 patients with bowel syndrome irritable, diarrheal and mixed variant (IBS-D and IBS-M), lasting for one year.

The study has two arms: Group 1: n=25 Treatment A e Group 2: n=25 Treatment B (with - Treatment A: 3 capsules/day of butyrate (625 mg) + 3 capsules/day PEA (200 mg) at a ratio of dosage of 3/1 - Treatment B: Placebo (3+3/day capsules of starch).

Eligible subjects with IBS will be randomized in a 1:1 ratio to treatment A or treatment B for six weeks. After the first treatment period, there is a 14-day washout period.

Hence, individuals will be treated with B/A treatment for additional six weeks, according to the crossover design.

In the two treatment periods, subjects will be required to complete a visual analogue score VAS questionnaire to assess gastrointestinal symptoms and Stool Bristol Scales. During the visit, the subjects will have to record Questionnaire Rome IV to evaluate their quality of life. At the same time, it will be theirs required to provide:

* fecal sample for the evaluation of the composition of fecal microbiota (Biomaplan Kit)
* a urine sample for the evaluation of intestinal permeability (Gastropack) a capillary blood sample and a serum sample for the detection of Zonulin (Kit Healthy gut and Immundiagnostik AG )
* a capillary blood sample and a serum sample for the detection of Zonulin (Kit Healthy gut and Immundiagnostik AG )

**Detailed Description:** Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon, characterized by relapsing and remitting mucosal inflammation. It presents with symptoms like bloody diarrhea, rectal urgency, fatigue, and abdominal pain. While various therapies are available for managing UC, including medications like amino salicylates, corticosteroids, immunomodulators, and biologics, there's ongoing research into supportive treatments like probiotics.

Probiotics are beneficial microorganisms that can positively influence gut health by modifying the gut microbiota, improving intestinal barrier function, and balancing immune response. Several studies have investigated their efficacy in UC management. Notably, the probiotic mixture VSL#3, containing strains of Lactobacillus and Bifidobacteria, has shown promising results in inducing remission in UC patients.

Other probiotic products like E. coli Nissle 1917, L. rhamnosus GG, and L. casei DG have also demonstrated effectiveness in maintaining disease remission or prolonging relapse-free periods in UC patients. The product Prolife 10 FORTE, containing multiple strains of Lactobacillus, Bifidobacteria, and Bacillus coagulans, along with prebiotic components and vitamins, has shown potential in positively influencing gut microbiota composition and metabolic activity in healthy individuals.

Based on these promising findings, further investigation is warranted to evaluate the potential of Prolife 10 FORTE in improving the gut microbiota composition of UC patients during the remission phase.

### Conditions Module

**Conditions:**

- Irritable Bowel Syndrome With Diarrhea

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** The study has two arms: Group 1: n=25 Treatment A e Group 2: n=25 Treatment B (with - Treatment A: 3 capsules/day of butyrate (625 mg) + 3 capsules/day PEA (200 mg) at a ratio of dosage of 3/1 - Treatment B: Placebo (3+3/day capsules of starch).

Eligible subjects with IBS will be randomized in a 1:1 ratio to the treatment A or treatment B for six weeks. After the first treatment period, there is a 14-day washout period.

Hence, individuals will be treated with B/A treatment for additional six weeks, according to the crossover design.

##### Masking Info

**Masking:** QUADRUPLE

**Masking Description:** Double-blind

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 50

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Treatment : 3 capsules/day of butyrate (625 mg) + 3 capsules/day PEA (200 mg) at a ratio of dosage of 3/1

**Intervention Names:**

- Dietary Supplement: ButirBioma + PeaBioma

**Label:** ButirBioma+PeaBioma

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Treatment Placebo :(3+3/day capsules of starch).

**Intervention Names:**

- Dietary Supplement: Placebo

**Label:** Placebo

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- ButirBioma+PeaBioma

**Description:** randomized in a 1:1 ratio to treatment Butir+Pea or treatment with Placebo for six weeks. After the first treatment period, there is a 14-day washout period.

**Name:** ButirBioma + PeaBioma

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Placebo

**Description:** Placebo( 3+3 cps/die)

**Name:** Placebo

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** Collection of faecal sample for the assessment of the faecal microbiota composition ( rRNA16S) The 16S rRNA gene is a bacterial ribosomal gene and a part of the 30S subunit which is used in the identification, characterization, and classification of various bacteria. Samples were normalized, pooled, and run on Illumina MiSeq , in order to evaluate the composition of gut microbiota in terms of bacterial diversity ( alfa and beta) and abundance and any variability associated with the treatment.

**Measure:** Evaluation of the variation of gut microbiota composition (Microbiota test )

**Time Frame:** 9 months

#### Secondary Outcomes

**Description:** 1. Analysis of mannitol( normal range 15-25%), lactulose( n.r. 0,45%-0,75%), sucrose(normal \< 0,15%) and sucralose( normal\<1,5%); L/M (normal \<0.03%; borderline 0,03%-0,09%; \>0.09 severe):
2. a capillary blood sample for the detection of Zonulin (Healthy gut Kit) )/Immundiagnostik AG )( normal cut-off 6-10 ng/mL)

**Measure:** Evaluation of intestinal permeability(4 sugar test: Gastropack)

**Time Frame:** 12 months

**Description:** Every evening during the two treatment periods, subjects must record a VAS(Visual Analogue Scale : 1-10; 1= non pain; 10= worst pain possible) questionnaire to assess gastrointestinal symptoms and the Stool Bristol Scale.( 1-7; normal 3-4)

**Measure:** Evaluation of Gastrointestinal symptoms( questionary)

**Time Frame:** 4 months

**Description:** At the visit time points, subjects will have to record the IBS-SSS score( points 75-174 mild, 175-300 moderate; \>300 severe)

**Measure:** Evaluation of Quality of Life (IBS-SSS score) (questionary)

**Time Frame:** 4 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* ● IBS patients (both males and females) with positive diagnosis based on Rome IV criteria (IBS-D and IBS-M)

  * Age in the range 18-70 years
  * Subjects capable of conforming to the study protocol
  * Subjects who have given their free and informed consent

Exclusion Criteria:

-Any relevant organic, systemic or metabolic disease, including celiac disease, IDDM (Insulin- Dependant Diabetes Mellitus), Insulin-Independent Diabetes Mellitus, metabolic syndrome, pelvic organ prolapses, urinary incontinence, ulcerative colitis, Crohn's disease, microscopic colitis, infectious colitis, ischemic colitis, complicated diverticular disease.

* Subjects with untreated food intolerance, i.e. remaining symptomatic despite the withdrawal of the suspected food
* Prior major gastrointestinal surgeries
* Females of childbearing potential, in the absence of effective contraceptive methods
* Subjects who become unable to conform to protocol
* Subjects who are continuously taking contact laxatives
* Subjects who are treated continuously with glucocorticoids, anti-histaminergic and mast cell stabilizer drugs
* Subjects who are treated continuously with trimebutine
* Recent history or suspicion of alcohol abuse or drug addiction
* Subjects who are treated with antibiotics or probiotics

**Healthy Volunteers:** True

**Maximum Age:** 70 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Padua

**Country:** Italy

**Facility:** Edoardo Vinvenzo Savarino

**Zip:** 35128

#### Overall Officials

**Official 1:**

**Affiliation:** University of Padova

**Name:** Edoardo Savarino, Prof,MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000003109

- Term: Colonic Diseases, Functional

- ID: D000003108

- Term: Colonic Diseases

- ID: D000007410

- Term: Intestinal Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000012817

- Term: Signs and Symptoms, Digestive

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M25118

- Name: Irritable Bowel Syndrome

- Relevance: HIGH

- As Found: Irritable Bowel Syndrome

- ID: M7159

- Name: Diarrhea

- Relevance: HIGH

- As Found: Diarrhea

- ID: M6336

- Name: Colonic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6337

- Name: Colonic Diseases, Functional

- Relevance: LOW

- As Found: Unknown

- ID: M10444

- Name: Intestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15622

- Name: Signs and Symptoms, Digestive

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000043183

- Term: Irritable Bowel Syndrome

- ID: D000013577

- Term: Syndrome

- ID: D000003967

- Term: Diarrhea

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Analg

- Name: Analgesics

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M340341

- Name: Palmidrol

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
