Exposure 1: Visceral hypersensitivity or phenotype suggestive of IBSExposure 2: Changes in anorectal motor function or compliance.
Exposure 1: Visceral hypersensitivity or phenotype suggestive of IBS: Assess the relation between the exposure and the outcome which is persistent symptoms in the patients with quiescent disease.
Exposure 2: Changes in anorectal motor function or compliance.: Assess the relation between the exposure and the outcome which is persistent symptoms in the patients with quiescent disease.
Study summary
Active inflammatory bowel disease (IBD) causes disabling symptoms such as diarrhea, involuntary loss of bowel control, abdominal pain and urges to pass stool. However, even patients with inactive IBD frequently experience such symptoms. The cause is not well understood and the functionality of the bowel in IBD patients is underexplored.
Earlier studies show a wide range of results, but most find that patients with IBD in remission are up to four times as likely to report gastrointestinal symptoms when compared to healthy controls.
Chronic inflammation may cause changes of the bowel wall, like increased collagen deposits (fibrosis) and thus cause symptoms, but the absence of active inflammation in combination with presence of symptoms may also be regarded as resembling the clinical condition of irritable bowel syndrome (IBS).
IBS is characterized by abdominal pain and changes in stool frequency and consistence and is often associated with disorders like depression and anxiety. Up to a third of IBD patients without signs of disease activity meet the criteria for IBS (irritable bowel syndrome. It can be speculated that an IBD diagnosis is a distressing event that can induce mood disorders, and an IBS-like condition.
Characterization of IBS patients relies on the Rome IV symptom criteria, symptom severity scales and measurements of rectal sensibility and rectal compliance using a barostat procedure.
Motor function assessment relies on anorectal manometry which detects abnormalities of muscle function and coordination. Recently, a standardized high-resolution anorectal manometry protocol (HRAM) was published which also evaluates sensitivity and compliance. The level of agreement between the barostat method and the HRAM testing procedure regarding sensibility and rectal compliance is largely unknown.
Recent studies have associated gut microorganisms, genetic factors, and proteins with various aspects of IBD. There is evidence that these potential markers may reflect non-inflammatory processes such as fibrosis.
The aim of this study is to explore the anorectal function in symptomatic patients with inactive IBD compared to healthy volunteers and asymptomatic patients, evaluate symptom severity and psychological parameters and perform molecular characterization.
The level of agreement of rectal sensitivity and compliance measurements with the barostat method and HRAM protocol will also be evaluated.
Eligibility
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
Accepted
Inclusion Criteria:
* Healthy volunteers
* Symptomatic IBD patients: Moderate to severe IBD in remission with persistent symptoms as reported by symptom index and short health scale.
* Asymptomatic IBD patients: moderate to severe IBD in remission without symptoms
Exclusion Criteria:
Healthy volunteers:
* gastrointestinal disease, functional gastrointestinal symptoms,
* psychiatric disease
* anal or pelvic surgery, inclusive interventions during delivery
* diabetes, cardiovascular, renal, or hepatic disease,
* concurrent or recent treatment with drugs affecting intestinal function or mood (antidepressants), nutritional supplements or herb products affecting intestinal function (probiotics), abuse of alcohol or drugs, and a recent (\< 2 weeks) history of systemic steroid therapy.
IBD patients
* active disease
* anal or pelvic surgery, inclusive interventions during delivery
* diabetes, cardiovascular, renal, or hepatic disease,
* concurrent or recent treatment with drugs affecting intestinal function or mood (antidepressants), nutritional supplements or herb products affecting intestinal function (probiotics), abuse of alcohol or drugs, and a recent (\< 2 weeks) history of systemic steroid therapy. Patients taking antidiarrhoeal or laxatives can be included after a 48 h washout period.
Primary outcome measure(s)
Rectal compliance testing with the HRAM and Barostat methods — 15 minnutes RC is defined as the relation between volume (ml) respective pressure (mmHg) at half the maximum volume observed and at thresholds for first sensation, first urge, intense urge and maximum tolerated volume.
Rectal sensitivity testing with whit the HRAM and Barostat methods — 15 minutes RS is defined as the volume (ml) respective pressure (mmHg) observed at 4 (HRAM) respective 5 (Barostat) predefined sensation thresholds.
Anal squeeze pressure — 3 minutes Anal pressure in mmHg assessed from the best of three short squeezes (5seconds) and a prolonged squeeze of 30 seconds during the HRAM investigation.
Anal rest pressure — 3 minutes Anal rest pressure in mmHg assessed during the HRAM investigation.
Anorectal coordination during simulated defecation — 2 minutes Binary outcome. Anorectal coordination is assessed from the changes in rectal and anal pressure during simulated defecation. The outcomes are: Effective simulated defecation: yes/no
Dyssynergic defecation — 2 minutes Categorical binary outcome. Anorectal coordination is assessed from the changes in rectal and anal pressure during simulated defecation. The outcome is: dyssynergic defecation: yes/no
GI symptoms based on the GSRS-IBS questionaire — 10 minutes The answers are converted to a numerical value where the higher score corresponds to worse symptoms.
GI symptoms based on the IBS symptom severity index — 10 minutes The answers are converted to a numerical value where the higher score corresponds to worse symptoms.
GI specific anxiety based on the Visceral sensitivity index — 10 minutes The answers are converted to a numerical value where the higher score corresponds to worse symptoms.
Symptom severity based on the Symptomatic severity module (PHQ 12) — 10 minutes The answers are converted to a numerical value where the higher score corresponds to worse symptoms.
Assessment of personality using the NEO-FFI-3questionnaire (Big five inventory) — 20 minutes The NEO-FFI is a 44-item personality inventory that examines a person's Big Five personality traits (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism). Each item is assigned a value between 1 to 5 by the participant. Scores for each of the 5 personality traits are calculated and interpreted with the help of the adequate tables.
Pathogenic variants — 30 minutes Arrays such as Illumina Global Screening Array and available exonic content databases like ClinVar, will be used to define "Pathogenic" and "Likely Pathogenic" variants in the likelihood of developing a phenotype and the frequency of such alleles within a given population.
Genetical risk score. — 30 minutes The liability for the symptomatic phenotype will be calculated by the sum of an individual's risk alleles, weighted by risk allele effect sizes derived from genome-wide associated study data.
Methylation status — 30 minutes Commercially available arrays such as the Illumina infinium 450K methylation array will also be used for the analyses of methylation status.
Aspects of proteomics — 30 minutes Olink precision inflammatory panel allows simultaneous analysis of 92 inflammation-related protein biomarkers, both in serum and in the rectal mucosa. Thereafter, we will use the Ingenuity Pathway Analysis (IPA) which allows for matching the results of our data against earlier IPA analyses.
Aspects of microbiome. — 30 minutes Fecal microbiota as well as mucosa-associated microbiota will be analysed both for qualitative and quantitative composition with both 16S-RNA sequencing and next-generation metagenomic sequencing, to identify the bacterial profile in the patients.
Aspects of transcriptome — 30 minutes Blood samples (Pax-gene tubes) and Rectal biopsies will be used for extraction of miRNA and subsequent analysis. In order to analyze the total RNA expression, Next Generation Sequencing (NGS) will be used.
The correlation between proteomics in the mucosa and in blood — 30 minutes Olink® precision proteomics inflammatory panel which allows simultaneous analysis of 92 inflammation-related protein biomarkers, both in serum and in the rectal mucosa.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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