The Use of Directed Probiotics in ME/CFS: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

This clinical study aims to evaluate the use of i3.1 probiotic in participants who meet the Institute of Medicine (Canadian Consensus Criteria) case definition for ME/CFS and who may or may not be diagnosed with irritable bowel syndrome (IBS). The main questions it aims to answer are:

• how effective is the usage of the i3.1 probiotic to reduce gastrointestinal (GI) inflammation and normalize the GI and systemic/brain interface?
• how well is it working on IBS severity? The study sample is 100 male and female participants aged 45 to 70 years with ME/CFS (per the Canadian Consensus Criteria); one-half of the participants will have co-morbid IBS (per Rome IV criteria). Participants will receive an i3.1 or a placebo and be assessed at baseline, at eight weeks, and at 12 weeks (four weeks post-treatment completion).

Study Overview

• Status: Recruiting
• Conditions: IBS - Irritable Bowel Syndrome; ME/CFS
• Intervention / Treatment: Drug: Floradapt Intensive GI; Other: Placebo

Detailed Description

This single-site comparison study will be performed on 100 participants, 45 to 70 years of age, who meet the Institute of Medicine (Canadian Consensus Criteria) case definition for ME/CFS and who may or may not be diagnosed with the irritable bowel syndrome (IBS), according to the Rome IV criteria. In this study, we will evaluate using the i3.1 probiotic compared to placebo. This is a randomized, placebo-controlled trial with four study arms that will include 25 participants per arm: Individuals with ME/CFS with and without IBS, who will take either the active medication i3.1 or placebo.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nancy Klimas, MD; Phone Number: 9542622855; Email: nklimas@nova.edu
• Study Contact Backup: Name: Devra Cohen, MPH; Phone Number: 9542621487; Email: dcohen1@nova.edu

Study Locations

• United States
  • Florida
    • Fort Lauderdale, Florida, United States, 33314-7796
      • Recruiting
      • Institute for Neuroimmune Medicine
      • Contact: Oleksandra Shchebet; Phone Number: 954-262-2896; Email: kanekastudy@nova.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria: eligible if all of the following apply:

• Meets IOM ME/CFS case definition criteria,
• Co-morbid IBS: meets RomeIV criteria for alternating or diarrhea-predominant IBS as reported during screening (technically diagnosed by a physician),
• Able to provide consent to study,
• Patients of childbearing potential must practice effective contraception during the study and be willing to continue contraception for at least six months after the intervention,
• agrees to participate in online surveys and follow-up visits.

Exclusion Criteria: ineligible if any of the following apply:

• Probiotics in the past eight weeks,
• Antibiotics in the past eight weeks,
• Pregnancy or lactating women,
• Medical conditions including short bowel syndrome, celiac disease, biliary disease, pancreatitis, inflammatory bowel disease (Crohn's disease, ulcerative colitis), severe cardiovascular, neurological condition, or liver failure,
• Gastrointestinal surgery within six months of study entry,
• History of psychiatric disorder, alcohol or illicit drug abuse.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Individuals with ME/CFS with IBS on active medication; Individuals with ME/CFS with IBS take Floradapt Intensive GI (another name i3.1), one high dose capsule (>3x10 to the ninth power) once daily for eight weeks.	Drug: Floradapt Intensive GI; one capsule daily for the eight week intervention; Other Names: i3.1
Placebo Comparator: Individuals with ME/CFS with IBS on placebo; Individuals with ME/CFS with IBS take a placebo, one capsule once daily for eight weeks.	Other: Placebo; one capsule daily for the eight week intervention
Active Comparator: Individuals with ME/CFS without IBS on active medication; Individuals with ME/CFS without IBS take Floradapt Intensive GI (another name i3.1), one high dose capsule (>3x10 to the ninth power) once daily for eight weeks.	Drug: Floradapt Intensive GI; one capsule daily for the eight week intervention; Other Names: i3.1
Placebo Comparator: Individuals with ME/CFS without IBS on placebo; Individuals with ME/CFS without IBS take a placebo, one capsule once daily for eight weeks.	Other: Placebo; one capsule daily for the eight week intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Intervention-Related Adverse Events [Safety]	Safety will be assessed by documenting the frequency and severity of adverse events using a standardized form at each visit.	from baseline to the eight week visit
The Measurement of Biomarker Response to an Intervention in the Blood [Efficacy]	The inflammation biomarkers panel will be measured at baseline and during the eight-week visit. Inflammation biomarkers analyses (such as zonulin, LPS (lipopolysaccharide) endotoxin, LBP (lipopolysaccharide-binding protein)	from baseline to the eight week visit
level of CRP (C-reactive protein)	CRP (C-reactive protein) will be measured at baseline and the eight-week visit (The Measurement of Biomarker Response)	from baseline to the eight week visit
The pro-inflammatory cytokines level e.g. IL-1, IL-6, and TNF-α	The Measurement of Biomarker Response : cytokine panel.	from baseline to the eight week visit
The Symptom Severity Measurement [Efficacy]	The symptom severity will be measured as a change of scores on the DePaul Symptom Questionnaire (DSQ) from baseline to eight-week visit. The severity and frequency are calculated on the Likert scale, where for severity 0 refers to symptoms not present, and 4 is for very severe, and for the frequency: 0 is for none of the time, and 4 is for all of the time. The score range is from 0 to 216. A higher score means a worse outcome (symptoms are present more often with more severity).	from baseline to the eight week visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Impact on the Irritable Bowel Syndrome (IBS) Severity	The impact on the Irritable Bowel Syndrome (IBS) severity will be assessed by response to intervention based on the change in score on the IBS-SSS (Irritable Bowel Syndrome Symptom Severity Scale) questionnaire from a baseline visit to an eight-week visit. Scores response on a 100-point visual analogue scale range from 0 to 500. Subjects can be categorized as mild (75-175), moderate (175-300), or severe (>300) IBS. A decrease of 50 points is associated with a clinically meaningful improvement.	from baseline to the eight week
The IBS-related Quality of Life Measurement	The measurement will be provided using the IBS-QOL (the Irritable Bowel Syndrome Quality of Life Measurement) questionnaire every visit from baseline to week eight. Each item is related on the Likert scale, ranging from 1 to 5 (1 as "not at all", 5 as "extremely"). Total score ranges from 34 to 170; higher scores mean a lower life quality. A decrease of 10 points is a clinically meaningful improvement.	from the eight week visit to the 12 week visit

Collaborators and Investigators

• Sponsor: Nova Southeastern University
• Investigators: Principal Investigator: Nancy Klimas, MD, Nova Southeastern University, Institute for Neuroimmune Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Estimated): February 24, 2026
• Study Completion (Estimated): February 24, 2026

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: January 17, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Musculoskeletal Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Pathologic Processes; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Intestinal Diseases; Infections; Disease; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Colonic Diseases, Functional; Central Nervous System Infections; Fatigue Syndrome, Chronic; Irritable Bowel Syndrome; Syndrome; Encephalomyelitis
• Other Study ID Numbers: 2020-631

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No