Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06413004
Status:
RECRUITING
Last Update Posted:
2024-05-14
First Post:
2024-05-06
Brief Title:
Brachyspira and Intestinal Allergy-like Immune Reactions in Patients With Irritable Bowel Syndrome IBS
Sponsor:
Magnus Simrén
Organization:
Sahlgrenska University Hospital Sweden
Study Overview
Official Title:
Brachyspira and Intestinal Allergy-like Immune Reactions in Patients With Irritable Bowel Syndrome IBS
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The aim of this study is to define local immune responses in the GI tract to food antigens in IBS patients with and without Brachyspira infection using advanced imaging We hypothesize that Brachyspira infection can cause IBS symptoms by inducing loss of oral tolerance to dietary antigens through development of food-specific intestinal immune reactions and subsequent development of visceral hypersensitivity
During this study the investigators will perform either confocal laser endomiscroscopy CLE or colonoscopic antigen provocation test COLAP to test to which food items the participants react to Furthermore the investigators will perform rectal barostat examination and a sigmoidoscopy without laxatives The investigators will collect biological samples and the participants will complete several questionnaires
During this study the investigators will perform either confocal laser endomiscroscopy CLE or colonoscopic antigen provocation test COLAP to test to which food items the participants react to Furthermore the investigators will perform rectal barostat examination and a sigmoidoscopy without laxatives The investigators will collect biological samples and the participants will complete several questionnaires
Detailed Description:
The aim of this study is to define local immune responses in the GI tract to food antigens in IBS patients with and without Brachyspira infection using advanced imaging The investigators hypothesize that Brachyspira infection can cause IBS symptoms by inducing loss of oral tolerance to dietary antigens through development of food-specific intestinal immune reactions and subsequent development of visceral hypersensitivity
Visit 1 inclusion questionnaires blood rectal barostat examination Visit 2 questionnaires blood stool diaries food and stool sigmoidoscopy without laxantives Allergologist visit skin prick test and interpretation blood results Visit 3 stool confocal laser endomicroscopy CLE OR colonoscopic antigen provocation test COLAP
Visit 45 and 6 only if the CLE or COLAP was positive for at least 1 food item
Visit 4 questionnaires and dietician-led instruction which food item to exclude positive food items during CLECOLAP exclusion for 4 weeks Visit 5 questionnaires stool diary instructions re-introduction food items Visit 6 questionnaires
QUESTIONNAIRES Baseline questionnaires demographic symptoms symptommedicationdiet history co-morbid medical conditions
IBS symptoms IBS-Symptom Severity Scale IBS-SSS and Gastrointestinal Symptom Rating Scale GSRS-IBS
Psychological distress Hospital Anxiety and Depression Scale HADS Patient Health Questionnaire PHQ-9 both visit 1456 generalized Anxiety Disorder 7-item scale GAD-7
Somatization PHQ-15 for the number and severity of bodily symptoms
Gastrointestinal specific anxiety Visceral Sensitivity Index VSI
Sensitivity Central Sensitization Inventory CSI
Food avoidance and restriction ARFID
Stool habits and GI symptoms 14-day GI symptom diary based on Bristol Stool Form Scale BSFS
Quality of life IBS-Quality of Life QOL
Food intake 4-days food diary MealQ
COLONOSCOPIC ALLERGEN PROVOCATION TEST COLAP
A local allergen provocation test where dietary antigens soy wheat egg gluten and milk with saline and histamine as negative and positive controls respectively are injected in the rectosigmoid mucosa similar to skin prick test used for clinical allergy testing
The intestinal reaction is determined visually wheal and flare reaction and biopsies are taken to characterize the immune response
Bowel preparation before the investigation follows the normal clinical routine for colonoscopy and iv sedatives and opioids are given during the investigation according to clinical routines at the endoscopy unit
CONFOCAL LASER ENDOMICROSCOPY CLE gastroscopy
A probe-based endoscopic technique to study intestinal food reactions after iv injection of fluorescein
Disruption of the small intestinal barrier in duodenum upon exposure to food antigens soy wheat egg gluten milk and control can be determined
VISCERAL SENSITIVITY
Rectal barostat sensitivity measurement With the rectal barostat the investigators can measure the rectal sensitivity A balloon is inserted and inflated in the rectum in a controlled setting The patient indicates when defined sensory thresholds are reached first feeling of the balloon urge to empty bowel discomfort or pain When the patient indicates discomfort or pain or another reason to stop the balloon inflation will be stopped
SIGMOIDOSCOPY
Flexible sigmoidoscopy without bowel preparation to interfere as little as possible with the normal gut microenvironment fresh biopsies for specific analyses and biopsies stored for subsequent analyses
BIOLOGICAL SAMPLES
Blood - and plasma samples Fasting blood samples are taken for routine blood tests exclusion of organic diseases and to determine the metabolic profile and genetic and immunological markers of relevance to intestinal function and nerve function Serum samples will be analyzed with nuclear magnetic resonance NMR for metabolomic profile and microbial composition
Fecal - and urine sample The investigators will characterize the composition and function of the metabolome in detail via 16S analysis metagenomics transcriptomics metabolomics cell culture and cell count Urine and fecal samples will also be analyzed with nuclear magnetic resonance NMR for metabolomic profile and microbial composition
Biopsies location based on the performed endoscopic examination The investigators will conduct a detailed analysis of immune cells proteins nerve cells and intestinal bacteria which will allow detailed mapping of intestinal function with respect to nerve immune and barrier function
Visit 1 inclusion questionnaires blood rectal barostat examination Visit 2 questionnaires blood stool diaries food and stool sigmoidoscopy without laxantives Allergologist visit skin prick test and interpretation blood results Visit 3 stool confocal laser endomicroscopy CLE OR colonoscopic antigen provocation test COLAP
Visit 45 and 6 only if the CLE or COLAP was positive for at least 1 food item
Visit 4 questionnaires and dietician-led instruction which food item to exclude positive food items during CLECOLAP exclusion for 4 weeks Visit 5 questionnaires stool diary instructions re-introduction food items Visit 6 questionnaires
QUESTIONNAIRES Baseline questionnaires demographic symptoms symptommedicationdiet history co-morbid medical conditions
IBS symptoms IBS-Symptom Severity Scale IBS-SSS and Gastrointestinal Symptom Rating Scale GSRS-IBS
Psychological distress Hospital Anxiety and Depression Scale HADS Patient Health Questionnaire PHQ-9 both visit 1456 generalized Anxiety Disorder 7-item scale GAD-7
Somatization PHQ-15 for the number and severity of bodily symptoms
Gastrointestinal specific anxiety Visceral Sensitivity Index VSI
Sensitivity Central Sensitization Inventory CSI
Food avoidance and restriction ARFID
Stool habits and GI symptoms 14-day GI symptom diary based on Bristol Stool Form Scale BSFS
Quality of life IBS-Quality of Life QOL
Food intake 4-days food diary MealQ
COLONOSCOPIC ALLERGEN PROVOCATION TEST COLAP
A local allergen provocation test where dietary antigens soy wheat egg gluten and milk with saline and histamine as negative and positive controls respectively are injected in the rectosigmoid mucosa similar to skin prick test used for clinical allergy testing
The intestinal reaction is determined visually wheal and flare reaction and biopsies are taken to characterize the immune response
Bowel preparation before the investigation follows the normal clinical routine for colonoscopy and iv sedatives and opioids are given during the investigation according to clinical routines at the endoscopy unit
CONFOCAL LASER ENDOMICROSCOPY CLE gastroscopy
A probe-based endoscopic technique to study intestinal food reactions after iv injection of fluorescein
Disruption of the small intestinal barrier in duodenum upon exposure to food antigens soy wheat egg gluten milk and control can be determined
VISCERAL SENSITIVITY
Rectal barostat sensitivity measurement With the rectal barostat the investigators can measure the rectal sensitivity A balloon is inserted and inflated in the rectum in a controlled setting The patient indicates when defined sensory thresholds are reached first feeling of the balloon urge to empty bowel discomfort or pain When the patient indicates discomfort or pain or another reason to stop the balloon inflation will be stopped
SIGMOIDOSCOPY
Flexible sigmoidoscopy without bowel preparation to interfere as little as possible with the normal gut microenvironment fresh biopsies for specific analyses and biopsies stored for subsequent analyses
BIOLOGICAL SAMPLES
Blood - and plasma samples Fasting blood samples are taken for routine blood tests exclusion of organic diseases and to determine the metabolic profile and genetic and immunological markers of relevance to intestinal function and nerve function Serum samples will be analyzed with nuclear magnetic resonance NMR for metabolomic profile and microbial composition
Fecal - and urine sample The investigators will characterize the composition and function of the metabolome in detail via 16S analysis metagenomics transcriptomics metabolomics cell culture and cell count Urine and fecal samples will also be analyzed with nuclear magnetic resonance NMR for metabolomic profile and microbial composition
Biopsies location based on the performed endoscopic examination The investigators will conduct a detailed analysis of immune cells proteins nerve cells and intestinal bacteria which will allow detailed mapping of intestinal function with respect to nerve immune and barrier function
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