Assessment of Anorectal Function in Healthy Volunteers and Patients With Inflammatory Bowel Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Pathogenic variants
研究概览
简要总结
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.
详细描述
Anorectal function (ARF) disorders in patients with IBD cause disabling symptoms such as fecal incontinence, increases in the stool frequency, urgency and tenesmus.
Patients with IBD in remission frequently experience diarrhea, fecal incontinence and lower GI symptoms. However, ARF in IBD patients is underexplored.
Chronic mucosal inflammation may induce visceral hypersensitivity and rectal wall fibrosis, but the casual relationship is hypothetical.
The absence of active inflammation and the presence of symptoms resemble IBS leading to the speculation that an IBD diagnosis is a distressing event, and can induce mood disorders, and an IBS-like condition.
Anorectal manometry detects abnormalities of sphincter function and rectoanal coordination. Recently, a standardized HRAM protocol was published (The London consensus protocol) witch also evaluates rectal sensitivity (RS) and rectal compliance (RC).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Pathogenic variants
时间窗: 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.
Methylation status
时间窗: 30 minutes
Commercially available arrays such as the Illumina infinium 450K methylation array will also be used for the analyses of methylation status.
Anorectal coordination during simulated defecation
时间窗: 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
时间窗: 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 IBS symptom severity index
时间窗: 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
时间窗: 10 minutes
The answers are converted to a numerical value where the higher score corresponds to worse symptoms.
Anal squeeze pressure
时间窗: 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
时间窗: 3 minutes
Anal rest pressure in mmHg assessed during the HRAM investigation.
Symptom severity based on the Symptomatic severity module (PHQ 12)
时间窗: 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)
时间窗: 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.
Genetical risk score.
时间窗: 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.
Rectal compliance testing with the HRAM and Barostat methods
时间窗: 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.
Aspects of proteomics
时间窗: 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.
Rectal sensitivity testing with whit the HRAM and Barostat methods
时间窗: 15 minutes
RS is defined as the volume (ml) respective pressure (mmHg) observed at 4 (HRAM) respective 5 (Barostat) predefined sensation thresholds.
GI symptoms based on the GSRS-IBS questionaire
时间窗: 10 minutes
The answers are converted to a numerical value where the higher score corresponds to worse symptoms.
Aspects of microbiome.
时间窗: 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.
The correlation between proteomics in the mucosa and in blood
时间窗: 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.
Aspects of transcriptome
时间窗: 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.
次要结局
- The aggregate sensation intensity scores for pain(12 minutes)
- Depression using the Depression Module (PHQ-9)(15 minutes)
- Aanxiety using the Anxiety module (GAD-7)(15 minutes)
- Assessment of disease-specific quality of life using the IBS-qol questionnaire(15 minutes)
- The adaptive function of the rectum during barostat investigation(12 minutes)
- Stool consistence using the Bristol stool form scale(10 minutes)
- The aggregate sensation intensity scores for gas(12 minutes)
- Dyspeptic symptoms using the Nepean dyspepsia index(10 minutes)
- Incontinence using the Vaizey score for incontinence(10 minutes)
- Cough reflex during HRAM(2 minutes)
- RAIR reflex during HRAM(2 minutes)
- The aggregate sensation intensity scores for urgency(12 minutes)
- The aggregate sensation intensity scores for discomfort(12 minutes)