Effect of Sporebiotics in FD

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Dyspepsia, Dysbiosis

Intervention / Treatment
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* Dietary Supplement: spore-forming probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized placebo-controlled study in 2 parallel FD cohorts
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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spore-forming probiotic, sporebiotic, proton pump inhibitor, dyspepsia