Assessment of Anorectal Function in Patients With Inflammatory Bowel Disease

NCT05185609 | Recruiting

• 1 other identifier: Regionorebrolan 252641
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Inflammatory Bowel Diseases; Irritable Bowel Syndrome

Keywords

Anorectal function; Anorectal manometry; Rectal barostat

Outcome Measures

Primary Outcomes (18)

• Rectal compliance testing with the HRAM and Barostat methods

  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.

  15 minnutes

• Rectal sensitivity testing with whit the HRAM and Barostat methods

  RS is defined as the volume (ml) respective pressure (mmHg) observed at 4 (HRAM) respective 5 (Barostat) predefined sensation thresholds.

  15 minutes

• Anal squeeze pressure

  Anal pressure in mmHg assessed from the best of three short squeezes (5seconds) and a prolonged squeeze of 30 seconds during the HRAM investigation.

  3 minutes

• Anal rest pressure

  Anal rest pressure in mmHg assessed during the HRAM investigation.

  3 minutes

• Anorectal coordination during simulated defecation

  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

  2 minutes

• Dyssynergic defecation

  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

  2 minutes

• GI symptoms based on the GSRS-IBS questionaire

  The answers are converted to a numerical value where the higher score corresponds to worse symptoms.

  10 minutes

• GI symptoms based on the IBS symptom severity index

  The answers are converted to a numerical value where the higher score corresponds to worse symptoms.

  10 minutes

• GI specific anxiety based on the Visceral sensitivity index

  The answers are converted to a numerical value where the higher score corresponds to worse symptoms.

  10 minutes

• Symptom severity based on the Symptomatic severity module (PHQ 12)

  The answers are converted to a numerical value where the higher score corresponds to worse symptoms.

  10 minutes

• Assessment of personality using the NEO-FFI-3questionnaire (Big five inventory)

  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.

  20 minutes

• Pathogenic variants

  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.

  30 minutes

• Genetical risk score.

  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.

  30 minutes

• Methylation status

  Commercially available arrays such as the Illumina infinium 450K methylation array will also be used for the analyses of methylation status.

  30 minutes

• Aspects of proteomics

  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.

  30 minutes

• Aspects of microbiome.

  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.

  30 minutes

• Aspects of transcriptome

  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.

  30 minutes

• The correlation between proteomics in the mucosa and in blood

  Olink® precision proteomics inflammatory panel which allows simultaneous analysis of 92 inflammation-related protein biomarkers, both in serum and in the rectal mucosa.

  30 minutes

Secondary Outcomes (13)

• Cough reflex during HRAM

  2 minutes

• RAIR reflex during HRAM

  2 minutes

• The adaptive function of the rectum during barostat investigation

  12 minutes

• The aggregate sensation intensity scores for gas

  12 minutes

• The aggregate sensation intensity scores for urgency

  12 minutes

Study Arms (4)

Healthy volunteers

Healthy volunteers aged 18-to 65

Other: Exposure 1: Visceral hypersensitivity or phenotype suggestive of IBS; Other: Exposure 2: Changes in anorectal motor function or compliance.

Asymptomatic patients with quiescent IBD

Asymptomatic patients with IBD in remission.

Other: Exposure 1: Visceral hypersensitivity or phenotype suggestive of IBS; Other: Exposure 2: Changes in anorectal motor function or compliance.

Symptomatic patients with quiescent UC

Symptomatic patients with UC in remission

Other: Exposure 1: Visceral hypersensitivity or phenotype suggestive of IBS; Other: Exposure 2: Changes in anorectal motor function or compliance.

Symptomatic patients with quiescent CD with anorectal involvement

Symptomatic patients with CD with distal involvement of the colon or perianal disease

Other: Exposure 1: Visceral hypersensitivity or phenotype suggestive of IBS; Other: Exposure 2: Changes in anorectal motor function or compliance.

Interventions

Exposure 1: Visceral hypersensitivity or phenotype suggestive of IBS OTHER

Assess the relation between the exposure and the outcome which is persistent symptoms in the patients with quiescent disease.

Asymptomatic patients with quiescent IBD; Healthy volunteers; Symptomatic patients with quiescent CD with anorectal involvement; Symptomatic patients with quiescent UC

Exposure 2: Changes in anorectal motor function or compliance. OTHER

Assess the relation between the exposure and the outcome which is persistent symptoms in the patients with quiescent disease.

Asymptomatic patients with quiescent IBD; Healthy volunteers; Symptomatic patients with quiescent CD with anorectal involvement; Symptomatic patients with quiescent UC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Remission is defined as endoscopic absence of active inflammation and f-calprotectin \< 100 mg/kg. Moderate to severe disease is defined as patients treated with the immune modulating drugs thiopurine or methotrexate, and/or biological drugs infliximab, adalimumab, golimumab, vedolizumab or ustekinumab. Presence of symptoms is evaluated by the short health scale and symptom index questionnaires that all IBD patients fill before their visit to the outpatient ward.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Region Örebro County: lead

Study Sites (1)

University hospital Örebro

Örebro, 70185, Sweden

RECRUITING

Related Publications (23)

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• Kozeluhova J, Kotyza J, Balihar K, Krcma M, Cedikova M, Karbanova J, Kalis V, Janska E, Matejovic M. Risk of anal incontinence in women with inflammatory bowel diseases after delivery. Bratisl Lek Listy. 2017;118(6):328-333. doi: 10.4149/BLL_2017_072a.

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• Stewart DB Sr. Fecal Incontinence Among Patients With Crohn's Disease: Does Awareness Change Anything? Dis Colon Rectum. 2017 Aug;60(8):759-760. doi: 10.1097/DCR.0000000000000811. No abstract available.

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• Vollebregt PF, Visscher AP, van Bodegraven AA, Felt-Bersma RJF. Validation of Risk Factors for Fecal Incontinence in Patients With Crohn's Disease. Dis Colon Rectum. 2017 Aug;60(8):845-851. doi: 10.1097/DCR.0000000000000812.

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• Carrington EV, Scott SM, Bharucha A, Mion F, Remes-Troche JM, Malcolm A, Heinrich H, Fox M, Rao SS; International Anorectal Physiology Working Group and the International Working Group for Disorders of Gastrointestinal Motility and Function. Expert consensus document: Advances in the evaluation of anorectal function. Nat Rev Gastroenterol Hepatol. 2018 May;15(5):309-323. doi: 10.1038/nrgastro.2018.27. Epub 2018 Apr 11.

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• Brochard C, Siproudhis L, Ropert A, Mallak A, Bretagne JF, Bouguen G. Anorectal dysfunction in patients with ulcerative colitis: impaired adaptation or enhanced perception? Neurogastroenterol Motil. 2015 Jul;27(7):1032-7. doi: 10.1111/nmo.12580. Epub 2015 May 4.

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• Vanhoutvin SA, Troost FJ, Kilkens TO, Lindsey PJ, Jonkers DM, Venema K, Masclee A, Brummer RJ. Alternative procedure to shorten rectal barostat procedure for the assessment of rectal compliance and visceral perception: a feasibility study. J Gastroenterol. 2012 Aug;47(8):896-903. doi: 10.1007/s00535-012-0543-x. Epub 2012 Feb 24.

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Biospecimen

Retention: SAMPLES WITH DNA

Serum. Stool samples. Rectal mucosal biopsies.

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Irritable Bowel Syndrome

Interventions

Compliance

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colonic Diseases, Functional; Colonic Diseases

Intervention Hierarchy (Ancestors)

Elasticity; Mechanical Phenomena; Physical Phenomena

Study Officials

• Michiel van Nieuwenhoven, assoc prof

  University Hospital Örebro

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lucian Marinica Grando, phd student

CONTACT

0046196021794; lucian.marinica-grando@regionorebrolan.se

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2021
• First Posted: January 11, 2022
• Study Start: September 1, 2021
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: February 3, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)