Ignite Creation Date:
2024-05-06 @ 3:56 PM
Last Modification Date:
2024-10-26 @ 1:59 PM
Study NCT ID:
NCT04804046
Status:
TERMINATED
Last Update Posted:
2024-01-19
First Post:
2021-03-11
Brief Title:
Synbiotics and Post-op Crohns Disease
Sponsor:
University of Alberta
Organization:
University of Alberta
Study Overview
Official Title:
Defining Microbial and Immune Changes Following Synbiotic Supplementation in Post-operative Crohns Disease Patients
Status:
TERMINATED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Crohns disease CD is a lifelong incurable condition that causes inflammation of the intestinal tract of humans The exact cause of CD is unknown but genetics diet and the gut microbiome are all thought to play a major role Many patients with CD will require surgery to remove affected portions of the gut with ileocecal resections being the most common procedure performed Regrettably there is up to an 85 chance that disease returns to the surgical site Strong immune suppressive medications may help to prevent disease relapse However patients are then at risk of serious side effects Currently no ideal post-op care exists for CD patients
This study aims to assess whether a post-op synbiotic therapy ie probiotics plus dietary fiber prevents disease relapse in participants with CD To test this participants will consume probiotics strains of bifidobacteria before their surgery and then probiotics plus fiber supplements after surgery Probiotics are live bacteria that have been shown to reduce inflammation of the gut Fiber is given after surgery to help promote beneficial bacterial taxa and prevent less favorable bacterial taxa from triggering CD relapse Patients will take the supplements for 6 months following surgery They will be seen monthly to assess the effects of treatment on quality of life symptoms of disease recurrence inflammatory markers and the gut microbiome All patients will also undergo a colonoscopy at the end of the study to check for endoscopic reoccurrence
This study aims to assess whether a post-op synbiotic therapy ie probiotics plus dietary fiber prevents disease relapse in participants with CD To test this participants will consume probiotics strains of bifidobacteria before their surgery and then probiotics plus fiber supplements after surgery Probiotics are live bacteria that have been shown to reduce inflammation of the gut Fiber is given after surgery to help promote beneficial bacterial taxa and prevent less favorable bacterial taxa from triggering CD relapse Patients will take the supplements for 6 months following surgery They will be seen monthly to assess the effects of treatment on quality of life symptoms of disease recurrence inflammatory markers and the gut microbiome All patients will also undergo a colonoscopy at the end of the study to check for endoscopic reoccurrence
Detailed Description:
Crohns disease CD is characterized by chronic intestinal inflammation and commonly involves the ileocecal region Due to disease complications many patients with CD require an ileocecal resection ICR However disease often recurs postoperatively at the surgical anastomosis with endoscopic recurrence rates as high as 85 While the immunosuppressant infliximab has been shown to reduce endoscopic disease recurrence it was not shown to prevent clinical relapse The timing of infliximab treatment might be critical as starting infliximab immediately after surgery rather than at the time of post-surgical recurrence resulted in 1-year remission rates of 92 and 57 respectively Currently no ideal postoperative care exists for patients with CD Thus new approaches are required
The gut microbiome has long been thought to play a causative role in the high rates of CD recurrence following surgical resection Immediately following ICR a state of inflammation and oxidative stress promotes aerotolerant microbes at the expense of beneficial short-chain fatty acid SCFA-producing anaerobes The mucosal microbial composition in CD patients at the time of surgery is predictive of future disease relapse Specifically patients with a dominance of SCFA-producing anaerobic bacteria in the ileal mucosa at the time of surgical resection are more likely to remain in remission compared with patients which have a dominance of aerotolerant bacteria Nutritional adjuncts based on probiotics or prebiotics could be applied to shift gut microbial imbalances towards SCFA-producers
Though research is limited probiotics containing bifidobacteria but not lactobacilli have been shown to lessen mucosal inflammation and recurrence rates when provided immediately post ICR In a previous clinical trial it was found that patients with CD that started the probiotic VSL3 4 Lactobacillus 3 Bifidobacterium 1 Streptococcus strains immediately post surgery had reduced mucosal inflammatory cytokines and lower recurrence rates when compared to patients that started VSL3 at 3-months post surgery A smaller trial using VSL3 in combination with antibiotic treatment also showed lower rates of endoscopic recurrence at 3- and 12-months following surgery These results suggest that probiotic composition and treatment timing are critical for efficacy While synergy between probiotics and prebiotics might improve clinical effects the efficacy of synergistic synbiotics remains unknown The aims of this study are the following
AIM 1 Perform a parallel two-arm randomized controlled exploratory trial in CD patients undergoing ICR to determine the safety and tolerability of a synbiotic treatment
This is a pilot study in patients with CD undergoing ileocecal resection to evaluate the feasibility of supplementation with a synbiotic preparation that contains a mixture of resistant starch type 2 HiMaize 260 Ingredion arabinoxylan Naxus Bioactive and galactooligosaccharide Vivinal FrieslandCampina 24gd fibers plus probiotic bacteria Bifidobacterium longum spp longum R0175 Bifidobacterium animalis spp Lafti B94 Bifidobacterium bifidum R0071 Lallemand Health Solutions 3x109 CFUd Participants will be given the probiotics 2 days prior to surgery and then the synbiotic will both be given 7 days after surgery and will be consumed daily for 6 months Digestible maltodextrin will be used as a placebo control Maltodextrin GLOBE Plus 15 Ingredion A total of 36 volunteers will be enrolled stratified by sex and randomized to one of 2 groups via computer-generated numbers as well as blinded to their group allocation to reduce bias Safety and tolerability of synbiotic primary outcome will be determined by the percentage of participants who experience treatment emergent adverse events and serious adverse events Symptom and quality of life questionnaires will also be used to evaluate tolerance
AIM 2 Determine if synbiotic therapy attenuates mucosal and systemic inflammation and reduces rates of disease relapse
Each month clinical recurrence will be evaluated by Harvey Bradshaw Index and C-reactive protein serum cytokines TNF-α IL-6 IL-8 and IL-10 intestinal barrier markers LPS LPS-binding protein and zonulin and fecal calprotectin levels will be measured At 6-months endoscopic recurrence will be determined by Rutgeerts Index and biopsies will be taken for the assessment of mucosal inflammation
AIM 3 Evaluate the impact on compositional and functional features of the fecal microbiota and to characterize associations between clinical and microbial outcomes
Fecal samples will be collected each month for the characterization of the microbiota by 16S rRNA gene sequencing Fecal concentrations of SCFAs and bile acids will also be determined as functional measures of the gut microbiota Associations between clinical outcomes and microbiota features will be assessed to identify signatures that predict the synbiotic impact
The gut microbiome has long been thought to play a causative role in the high rates of CD recurrence following surgical resection Immediately following ICR a state of inflammation and oxidative stress promotes aerotolerant microbes at the expense of beneficial short-chain fatty acid SCFA-producing anaerobes The mucosal microbial composition in CD patients at the time of surgery is predictive of future disease relapse Specifically patients with a dominance of SCFA-producing anaerobic bacteria in the ileal mucosa at the time of surgical resection are more likely to remain in remission compared with patients which have a dominance of aerotolerant bacteria Nutritional adjuncts based on probiotics or prebiotics could be applied to shift gut microbial imbalances towards SCFA-producers
Though research is limited probiotics containing bifidobacteria but not lactobacilli have been shown to lessen mucosal inflammation and recurrence rates when provided immediately post ICR In a previous clinical trial it was found that patients with CD that started the probiotic VSL3 4 Lactobacillus 3 Bifidobacterium 1 Streptococcus strains immediately post surgery had reduced mucosal inflammatory cytokines and lower recurrence rates when compared to patients that started VSL3 at 3-months post surgery A smaller trial using VSL3 in combination with antibiotic treatment also showed lower rates of endoscopic recurrence at 3- and 12-months following surgery These results suggest that probiotic composition and treatment timing are critical for efficacy While synergy between probiotics and prebiotics might improve clinical effects the efficacy of synergistic synbiotics remains unknown The aims of this study are the following
AIM 1 Perform a parallel two-arm randomized controlled exploratory trial in CD patients undergoing ICR to determine the safety and tolerability of a synbiotic treatment
This is a pilot study in patients with CD undergoing ileocecal resection to evaluate the feasibility of supplementation with a synbiotic preparation that contains a mixture of resistant starch type 2 HiMaize 260 Ingredion arabinoxylan Naxus Bioactive and galactooligosaccharide Vivinal FrieslandCampina 24gd fibers plus probiotic bacteria Bifidobacterium longum spp longum R0175 Bifidobacterium animalis spp Lafti B94 Bifidobacterium bifidum R0071 Lallemand Health Solutions 3x109 CFUd Participants will be given the probiotics 2 days prior to surgery and then the synbiotic will both be given 7 days after surgery and will be consumed daily for 6 months Digestible maltodextrin will be used as a placebo control Maltodextrin GLOBE Plus 15 Ingredion A total of 36 volunteers will be enrolled stratified by sex and randomized to one of 2 groups via computer-generated numbers as well as blinded to their group allocation to reduce bias Safety and tolerability of synbiotic primary outcome will be determined by the percentage of participants who experience treatment emergent adverse events and serious adverse events Symptom and quality of life questionnaires will also be used to evaluate tolerance
AIM 2 Determine if synbiotic therapy attenuates mucosal and systemic inflammation and reduces rates of disease relapse
Each month clinical recurrence will be evaluated by Harvey Bradshaw Index and C-reactive protein serum cytokines TNF-α IL-6 IL-8 and IL-10 intestinal barrier markers LPS LPS-binding protein and zonulin and fecal calprotectin levels will be measured At 6-months endoscopic recurrence will be determined by Rutgeerts Index and biopsies will be taken for the assessment of mucosal inflammation
AIM 3 Evaluate the impact on compositional and functional features of the fecal microbiota and to characterize associations between clinical and microbial outcomes
Fecal samples will be collected each month for the characterization of the microbiota by 16S rRNA gene sequencing Fecal concentrations of SCFAs and bile acids will also be determined as functional measures of the gut microbiota Associations between clinical outcomes and microbiota features will be assessed to identify signatures that predict the synbiotic impact
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None