search
Back to results

Effect of Sporebiotics in FD

Primary Purpose

Dyspepsia, Dysbiosis

Status
Completed
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
spore-forming probiotic
Placebo
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dyspepsia focused on measuring spore-forming probiotic, sporebiotic, proton pump inhibitor, dyspepsia

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • UZ Leuven

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

Cohort 1FD (on-PPI+sporebiotics)

Cohort 1FD (on-PPI+placebo)

Cohort 2FD (off-PPI+sporebiotics)

Cohort 2FD (off-PPI+placebo)

Arm Description

study procedures at inclusion (1) and after 8 weeks on-PPI+ sporebiotics (2) followed by 8 weeks on-PPI+ sporebiotics (open label)

study procedures at inclusion (1) and after 8 weeks on-PPI+ placebo (2) followed by 8 weeks on-PPI+ sporebiotics (open label)

study procedures at inclusion (1) and after 8 weeks of sporebiotics (2) followed by 8 weeks of sporebiotics (open label)

study procedures at inclusion (1) and after 8 weeks of placebo (2) followed by 8 weeks of sporebiotics (open label)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Safety of sporebiotics vs. placebo
number of adverse events with sporebiotics vs. placebo

Full Information

First Posted
June 3, 2019
Last Updated
February 15, 2021
Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
MY HEALTH
search

1. Study Identification

Unique Protocol Identification Number
NCT04030780
Brief Title
Effect of Sporebiotics in FD
Official Title
Effect of Spore-forming Probiotics in Functional Dyspepsia Patients: a Randomized Placebo-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
June 3, 2019 (Actual)
Primary Completion Date
July 7, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven
Collaborators
MY HEALTH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dyspepsia, Dysbiosis
Keywords
spore-forming probiotic, sporebiotic, proton pump inhibitor, dyspepsia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
randomized placebo-controlled study in 2 parallel FD cohorts
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
participants, care providers, investigators and outcomes assessor are blinded during the randomized placebo-controlled phase (8 weeks) but not during the open-label extension phase (8 weeks)
Allocation
Randomized
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1FD (on-PPI+sporebiotics)
Arm Type
Active Comparator
Arm Description
study procedures at inclusion (1) and after 8 weeks on-PPI+ sporebiotics (2) followed by 8 weeks on-PPI+ sporebiotics (open label)
Arm Title
Cohort 1FD (on-PPI+placebo)
Arm Type
Placebo Comparator
Arm Description
study procedures at inclusion (1) and after 8 weeks on-PPI+ placebo (2) followed by 8 weeks on-PPI+ sporebiotics (open label)
Arm Title
Cohort 2FD (off-PPI+sporebiotics)
Arm Type
Active Comparator
Arm Description
study procedures at inclusion (1) and after 8 weeks of sporebiotics (2) followed by 8 weeks of sporebiotics (open label)
Arm Title
Cohort 2FD (off-PPI+placebo)
Arm Type
Placebo Comparator
Arm Description
study procedures at inclusion (1) and after 8 weeks of placebo (2) followed by 8 weeks of sporebiotics (open label)
Intervention Type
Dietary Supplement
Intervention Name(s)
spore-forming probiotic
Intervention Description
spore-forming probiotic administered as 1 capsule twice daily (2,5 x 109 CFU per capsule) during 8 weeks
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
similar capsules administered twice daily
Primary Outcome Measure Information:
Title
Proportion of clinical responders (first 8 weeks) in sporebiotics vs. placebo
Description
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.
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Proportion of minimal clinical responders (first 8 weeks) in sporebiotics vs. placebo
Description
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.
Time Frame
8 weeks
Title
Change in weekly PDS symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups
Description
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.
Time Frame
8 weeks
Title
Change in weekly EPS symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups
Description
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.
Time Frame
8 weeks
Title
Change in weekly individual symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups
Description
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.
Time Frame
8 weeks
Title
Proportion of (minimal) clinical responders (3 of the last 4 weeks of treatment) in sporebiotics vs. placebo
Description
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.
Time Frame
8 weeks
Title
Weekly (minimal) clinical responder rates in sporebiotics vs. placebo
Description
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.
Time Frame
8 weeks
Title
Change in monthly PAGI-SYM score from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups
Description
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.
Time Frame
8 weeks
Title
Change in monthly PAGI-QOL score from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups
Description
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.
Time Frame
8 weeks
Title
Change in high-sensitivity C-reactive protein (hs-CRP) on sporebiotics vs. placebo and changes within-groups
Description
Change in hs-CRP (mg/L) sporebiotics vs. placebo and within-group by comparing pre- with post-treatment values.
Time Frame
8 weeks
Title
Change in peripheral blood mononuclear cells on sporebiotics vs. placebo and changes within-groups
Description
Change in proportion of PBMC (measured by flow-cytometry) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.
Time Frame
8 weeks
Title
Change in plasma cytokines on sporebiotics vs. placebo and changes within-groups
Description
Change in cytokines (measured by multiplex) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.
Time Frame
8 weeks
Title
Change in lipopolysaccharide-binding protein (LBP) on sporebiotics vs. placebo and changes within-groups
Description
Change in LBP (ng/mL) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.
Time Frame
8 weeks
Title
Change in stool microbiota on sporebiotics vs. placebo and changes within-groups
Description
Change in stool microbiota (quantitative microbiota profiles) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.
Time Frame
8 weeks
Title
Safety of sporebiotics vs. placebo
Description
number of adverse events with sporebiotics vs. placebo
Time Frame
16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tim Vanuytsel, MD PhD
Organizational Affiliation
Universitaire Ziekenhuizen KU Leuven
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Leuven
City
Leuven
ZIP/Postal Code
3000
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34358486
Citation
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;:
Results Reference
derived

Learn more about this trial

Effect of Sporebiotics in FD

We'll reach out to this number within 24 hrs