Effect of Sporebiotics in FD

Effect of Spore-forming Probiotics in Functional Dyspepsia Patients: a Randomized Placebo-controlled Trial

Single-site prospective interventional study aiming to demonstrate the effect of spore-forming probiotics on dyspeptic symptoms and blood, saliva and stool parameters in FD patients with and without acid suppression, compared to placebo.

Study Overview

• Status: Completed
• Conditions: Dyspepsia; Dysbiosis
• Intervention / Treatment: Dietary supplement: spore-forming probiotic; Other: Placebo

Detailed Description

Prospective randomized placebo-controlled study in 2 parallel FD cohorts (8 weeks) with open-label extension phase (8 weeks):

• cohort 1FD (on-PPI): study procedures at inclusion (1) and after 8 weeks on-PPI+ sporebiotics or placebo (2) followed by 8 weeks on-PPI+ sporebiotics (open label)
• cohort 2FD (off-PPI): study procedures at inclusion (1) and after 8 weeks of sporebiotics or placebo (2) followed by 8 weeks of sporebiotics (open label)

Clinical outcomes and blood, saliva and stool parameters will be assessed at the beginning and end of each treatment period (week 0, 8 and 16) with additional questionnaires after 1 month (week 4 and 12).

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients >18 years with FD diagnosis (Rome IV criteria)
• Male or female (not pregnant or lactating and using contraception or postmenopausal)
• Normal bowel habits (defecation once every 3 days up to 3 times a day)
• Witnessed written informed consent
• Access to home freezer (-18 to -20°C)
• Capable to understand and comply with the study requirements

Exclusion Criteria:

• Any active somatic or psychiatric condition that may explain dyspeptic symptoms (stable dose of single antidepressant allowed for psychiatric indication, no limitation for other indications)
• Predominant symptoms of gastro-esophageal reflux disease (GERD) or irritable bowel syndrome (IBS)
• Use of immunosuppressants or antibiotics <3 months
• History of major abdominal surgery (except for appendectomy, cholecystectomy or splenectomy)
• Personal history of diabetes mellitus type 1, celiac disease or inflammatory bowel disease
• Diabetes mellitus type 2 (including therapy)
• Active malignancy (including therapy)
• Known HIV, HBV or HCV infection (including therapy)
• Significant alcohol use (>10 units/weeks)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cohort 1FD (on-PPI+sporebiotics); study procedures at inclusion (1) and after 8 weeks on-PPI+ sporebiotics (2) followed by 8 weeks on-PPI+ sporebiotics (open label)	Dietary supplement: spore-forming probiotic; spore-forming probiotic administered as 1 capsule twice daily (2,5 x 109 CFU per capsule) during 8 weeks
Placebo Comparator: Cohort 1FD (on-PPI+placebo); study procedures at inclusion (1) and after 8 weeks on-PPI+ placebo (2) followed by 8 weeks on-PPI+ sporebiotics (open label)	Other: Placebo; similar capsules administered twice daily
Active Comparator: Cohort 2FD (off-PPI+sporebiotics); study procedures at inclusion (1) and after 8 weeks of sporebiotics (2) followed by 8 weeks of sporebiotics (open label)	Dietary supplement: spore-forming probiotic; spore-forming probiotic administered as 1 capsule twice daily (2,5 x 109 CFU per capsule) during 8 weeks
Placebo Comparator: Cohort 2FD (off-PPI+placebo); study procedures at inclusion (1) and after 8 weeks of placebo (2) followed by 8 weeks of sporebiotics (open label)	Other: Placebo; similar capsules administered twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of clinical responders (first 8 weeks) in sporebiotics vs. placebo	The Leuven Postprandial Distress Scale (LPDS) is a daily diary assessing the severity of 11 upper gastrointestinal symptoms scored from 0 (none) to 4 (very severe). A difference of 0.7 from baseline for the cardinal PDS symptoms (average of first 3 questions) will be used as a cut-off to determine clinical response by comparing averaged pre-treatment scores with the average score during the last week on treatment with sporebiotics vs. placebo. Only subjects with baseline score >1 (mild) will be included in the intention-to-treat and per-protocol analysis.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of minimal clinical responders (first 8 weeks) in sporebiotics vs. placebo	The Leuven Postprandial Distress Scale (LPDS) is a daily diary assessing the severity of 11 upper gastrointestinal symptoms scored from 0 (none) to 4 (very severe). Proportion of minimal clinical responders using the minimum clinically important difference (MCID) of 0.5 for the cardinal PDS symptoms (first 3 questions) in subjects with baseline score >1 (mild) will be compared between sporebiotics and placebo for both cohorts combined.	8 weeks
Change in weekly PDS symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups	The Leuven Postprandial Distress Scale (LPDS) is a daily diary assessing the severity of 11 upper gastrointestinal symptoms scored from 0 (none) to 4 (very severe). Change in weekly PDS symptoms (first 3 questions) will be compared within- and between-treatments for both cohorts combined.	8 weeks
Change in weekly EPS symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups	The Leuven Postprandial Distress Scale (LPDS) is a daily diary assessing the severity of 11 upper gastrointestinal symptoms scored from 0 (none) to 4 (very severe). Change in weekly EPS symptoms (questions 4+5) will be compared within- and between-treatments for both cohorts combined.	8 weeks
Change in weekly individual symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups	The Leuven Postprandial Distress Scale (LPDS) is a daily diary assessing the severity of 11 upper gastrointestinal symptoms scored from 0 (none) to 4 (very severe). Change in weekly individual symptoms will be compared within- and between-treatments for both cohorts combined.	8 weeks
Proportion of (minimal) clinical responders (3 of the last 4 weeks of treatment) in sporebiotics vs. placebo	Proportion of (minimal) clinical responders for the cardinal PDS symptoms (first 3 questions) in subjects with baseline score >1 (mild) will be compared for 3 of the last 4 weeks of treatment between sporebiotics and placebo for both cohorts combined.	8 weeks
Weekly (minimal) clinical responder rates in sporebiotics vs. placebo	Change in weekly proportions for the cardinal PDS symptoms (first 3 questions) in subjects with baseline score >1 (mild) will be compared within- and between-treatments for both cohorts combined.	8 weeks
Change in monthly PAGI-SYM score from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups	The Patient Assessment of GastroIntestinal SYMptom severity (PAGI-SYM) is a validated questionnaire assessing the severity of 20 symptoms scored from 0 (none) to 4 (very severe). Change in monthly scores will be compared within- and between-treatments for both cohorts combined.	8 weeks
Change in monthly PAGI-QOL score from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups	The Patient Assessment of GastroIntestinal Quality Of Life (PAGI-QOL) is a validated questionnaire assessing 30 items scored from 0 (all the time) to 5 (none of the time). Change in monthly scores will be compared within- and between-treatments for both cohorts combined.	8 weeks
Change in high-sensitivity C-reactive protein (hs-CRP) on sporebiotics vs. placebo and changes within-groups	Change in hs-CRP (mg/L) sporebiotics vs. placebo and within-group by comparing pre- with post-treatment values.	8 weeks
Change in peripheral blood mononuclear cells on sporebiotics vs. placebo and changes within-groups	Change in proportion of PBMC (measured by flow-cytometry) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.	8 weeks
Change in plasma cytokines on sporebiotics vs. placebo and changes within-groups	Change in cytokines (measured by multiplex) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.	8 weeks
Change in lipopolysaccharide-binding protein (LBP) on sporebiotics vs. placebo and changes within-groups	Change in LBP (ng/mL) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.	8 weeks
Change in stool microbiota on sporebiotics vs. placebo and changes within-groups	Change in stool microbiota (quantitative microbiota profiles) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.	8 weeks
Safety of sporebiotics vs. placebo	number of adverse events with sporebiotics vs. placebo	16 weeks

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: MY HEALTH
• Investigators: Principal Investigator: Tim Vanuytsel, MD PhD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Wauters L, Slaets H, De Paepe K, Ceulemans M, Wetzels S, Geboers K, Toth J, Thys W, Dybajlo R, Walgraeve D, Biessen E, Verbeke K, Tack J, Van de Wiele T, Hellings N, Vanuytsel T. Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2021 Oct;6(10):784-792. doi: 10.1016/S2468-1253(21)00226-0. Epub 2021 Aug 3. Erratum In: Lancet Gastroenterol Hepatol. 2021 Aug 27;:

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2019
• Primary Completion (Actual): July 7, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 15, 2021
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: proton pump inhibitor; dyspepsia; spore-forming probiotic; sporebiotic
• Additional Relevant MeSH Terms: Pathologic Processes; Signs and Symptoms, Digestive; Dyspepsia; Dysbiosis
• Other Study ID Numbers: S62043

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