Effect of Sporebiotics in FD
- Conditions
- DysbiosisDyspepsia
- Interventions
- Dietary Supplement: spore-forming probioticOther: Placebo
- Registration Number
- NCT04030780
- Lead Sponsor
- Universitaire Ziekenhuizen KU Leuven
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1FD (on-PPI+sporebiotics) spore-forming probiotic study procedures at inclusion (1) and after 8 weeks on-PPI+ sporebiotics (2) followed by 8 weeks on-PPI+ sporebiotics (open label) Cohort 2FD (off-PPI+sporebiotics) spore-forming probiotic study procedures at inclusion (1) and after 8 weeks of sporebiotics (2) followed by 8 weeks of sporebiotics (open label) Cohort 2FD (off-PPI+placebo) Placebo study procedures at inclusion (1) and after 8 weeks of placebo (2) followed by 8 weeks of sporebiotics (open label) Cohort 1FD (on-PPI+placebo) Placebo study procedures at inclusion (1) and after 8 weeks on-PPI+ placebo (2) followed by 8 weeks on-PPI+ sporebiotics (open label)
- Primary Outcome Measures
Name Time Method Proportion of clinical responders (first 8 weeks) in sporebiotics vs. placebo 8 weeks 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
Name Time Method Proportion of minimal clinical responders (first 8 weeks) in sporebiotics vs. placebo 8 weeks 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 individual symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups 8 weeks 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.
Change in monthly PAGI-QOL score from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups 8 weeks 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 8 weeks 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 8 weeks 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 8 weeks Change in cytokines (measured by multiplex) on sporebiotics vs. placebo and changes within-groups by comparing pre- with post-treatment values.
Change in weekly PDS symptoms from baseline (first 8 weeks) on sporebiotics vs. placebo and changes within-groups 8 weeks 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 8 weeks 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.
Proportion of (minimal) clinical responders (3 of the last 4 weeks of treatment) in sporebiotics vs. placebo 8 weeks 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 8 weeks 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 8 weeks 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 lipopolysaccharide-binding protein (LBP) on sporebiotics vs. placebo and changes within-groups 8 weeks 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 8 weeks 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 16 weeks number of adverse events with sporebiotics vs. placebo
Trial Locations
- Locations (1)
UZ Leuven
🇧🇪Leuven, Belgium