Alcat Based Elimination Diet for the Treatment of Irritable Bowel Syndrome; a Randomized Double Blind Sham Control Trial

Irritable bowel syndrome (IBS) is the most common GI condition with global prevalence ranging between 10-20%. Although the exact cause is not known there are increasing insights concerning the possible multifactorial etiology including low grade inflammation, neuromodulation, dysbiosis, impaired integrity of the intestinal barrier and more.

Currently, it is believed that changes in the microbiota may activate mucosal innate immune responses, resulting in increased epithelial permeability, activated nociceptive sensory pathways, and dysregulation of the enteric nervous system.

Nearly two thirds of patients with IBS perceive their GI symptoms to be food related, hence, food intolerance may be important factor in the pathogenesis. Diet is a part of IBS treatment but adherence, on the one hand, and restriction, on the other, remain a major problem. [Chey WD, Am J Gastroenterol,2016].

Confocal laser endomicroscopy (CLE) is a technique that permits real-time detection and quantification of changes in intestinal tissues and cells, including increases in intraepithelial lymphocytes and fluid extravasation through epithelial leaks.

Based on CLE analysis of IBS patients with a suspected food intolerance, exposure to candidate food antigens caused immediate breaks, increased intervillous spaces, and increased IELs in the intestinal mucosa. These changes are associated with patient responses to exclusion diets. [Fritscher-Ravens A et al, Gastroenterology. 2019, Gastroenterology. 2014] This technic, also efficient according to former studies, is costly and invasive.

The Alcat Test is a lab based immune stimulation test in which a patient's WBC's (white blood cell) are challenged with various substances including foods, additives, colorings, chemicals, medicinal herbs, functional foods, molds and pharmaceutical compounds. The Alcat Test objectively classifies a patient's response to each test substance as reactive, borderline or non-reactive. Based on these classifications, a customized elimination/rotation diet may be designed.

Study Overview

• Status: Completed
• Conditions: IBS - Irritable Bowel Syndrome
• Intervention / Treatment: Other: usual care; Dietary supplement: Alcat based personal diet; Dietary supplement: Standard balanced diet

Detailed Description

Diet therapies for IBS are becoming an important part of the treatment for patients with IBS [Lenhart A et al, J Neurogastroenterology Motil 2018] There are many types of elimination diets utilized by patients with IBS including personalized diets based upon mediator release testing and IgG (immunoglobulin G) antibody. These diets have the potential for tailor made personal diet but currently have little or no clinical evidence for efficacy.

Diet therapies, like medical therapies for IBS, should be properly evaluated in appropriate designed clinical trials.

It is also important to protect our patients with IBS from potentially ineffective, costly and unsafe intervention.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel, 5262000
    • Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Only adults (>18 years of age) meeting the Rome 4 Criteria for IBS D/M/U and who are willing to adhere to diet restrictions, will be eligible for entry into the study.
2. Patients with 'warning symptoms' (e.g., unexplained weight loss, history of GI cancer or inflammatory bowel disease, rectal bleeding etc) will be required to have had a detailed workup to exclude organic pathology prior to enrollment.
3. Participants will be allowed to continue their IBS medications (e.g., fiber, anti-spasmodics, antidepressants, loperamide, etc.) as long as they had been on stable doses for at least 30 days prior to entering the study and agreed not to change medications or dosages during the trial.
4. In addition, patients will be required to have active symptoms at the entry of the study as defined by having an IBSSSS score of >150 (0-500 scale).

Exclusion Criteria:

1. Patients will be excluded if they fulfill ROME 4 IBS C criteria
2. Have an inflammatory bowel disease, celiac or other inflammatory or gut disorder other than IBS.
3. Have active malignancy of any kind
4. If they are not able to eat PO
5. If they are Using NSAIDS more than once per month and within the 4 weeks prior to inclusion
6. If C reactive protein is above 2 times the normal value or if stool Calprotectin is above 200mcg/gr
7. If they had recent antibiotic use (within 1 month). -

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alcat based personal diet	Other: usual care; usual care; Dietary supplement: Alcat based personal diet; Alcat based personalized diet with dietician supervision and follow-up + usual care
Sham Comparator: Standard balanced diet	Other: usual care; usual care; Dietary supplement: Standard balanced diet; "Sham" standard balanced diet with dietician supervision and follow up + usual care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Irritable Bowel Syndrome (IBS) Symptom Severity Scale questionnaire	decrease of 50 points. Values range: 0-500	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Irritable Bowel Syndrome (IBS) Adequate Relief questionnaire	IBS-Adequate Relief (IBS-AR) is a dichotomous single item that asks participants "Over the past week have you had adequate relief of your IBS symptoms?	up to 8 weeks
Irritable Bowel Syndrome Quality of life questionnaire - specific for IBS (IBS-QoL)	Changes from baseline to Week 8 in IBS-QOL total and subscale scores . Values: 34-170	8 weeks
Irritable Bowel Syndrome Global Symptom Assessment (IBS-GSA) questionnaire	Compared to how you felt then, how would you rate your overall IBS symptoms during the past week? Possible answers are one of the following: Significantly relieved (+3); Moderately relieved (+2); A little bit relieved (+1); Unchanged (0); A little bit worse (-1); Moderately worse (-2); Significantly worse (-3). [ Rome Foundation]	4 and 8 weeks
Abnormal laboratory value - bio marker	decrease level - CRP (C reactive protein) milligrams per liter (mg/L)	8 weeks
Monitoring serum level of Syndecan-1 (Sdc1) ng/mL	Syndecan-1 (Sdc-1) is a type 1 transmembrane heparan sulfate proteoglycans that are implicated in maintenance of intestinal epithelial barrier. Sdc-1 is predominantly expressed by plasma cells and mucosal epithelial cells, such as intestinal epithelial cells. Changes of Sdc1 level in sera will be assessed primarily to the diet intervention and at the end of the diet after 8 weeks	8 weeks
Irritable Bowel Syndrome Global Improvement Scale (IBS-GIS)	Compared to the way you felt before you entered the study, have your IBS symptoms over the past 7 days been: 1) Substantially Worse, 2) Moderately Worse, 3)Slightly Worse, 4) No Change, 5) Slightly Improved, 6) Moderately Improved or 7) Substantially Improved. A responder is defined as a patient who answered "moderately improved" or "substantially improved".	up to 8 weeks

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Collaborators: Cell science systems

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): May 15, 2023
• Study Completion (Actual): May 15, 2023

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: November 13, 2022
• First Posted (Actual): November 15, 2022

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 21, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome
• Other Study ID Numbers: 6834-20-TA-CTIL

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