Optimizing Patient Treatment Involving Microbiome Integration for Specialized Therapeutics
概览
- 阶段
- 不适用
- 干预措施
- 未指定
- 疾病 / 适应症
- Inflammatory Bowel Diseases
- 发起方
- University of British Columbia
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Compare results of microbial analyses (including bacteriome and mycobiome) across three different sample types: intestinal washings and intestinal epithelial biopsy specimens taken during colonoscopy as well as fecal samples.
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
The goal of this prospective observational study is to determine if specific microbiome signatures can predict therapeutic responses in adult patients with Crohn's disease (CD), a form of inflammatory bowel disease (IBD), living in British Columbia, Canada. The main questions this study seeks to answer are:
- Can microbiome signatures across different sample types (fecal, intestinal washings, and intestinal epithelial biopsies) predict response to therapy in CD?
- How do microbiome profiles differ between active and quiescent CD and non-IBD controls?
Researchers will compare microbiome signatures in patients with active and inactive CD as well as non-IBD controls to see if there are any microbial signatures that predict response to therapy.
Participants will:
- Provide fecal and blood samples.
- Undergo intestinal washings and intestinal epithelial biopsy specimens taken during routine colonoscopy.
- Participate in a longitudinal follow-up over 12 months to monitor clinical, biochemical, and endoscopic responses to therapy.
详细描述
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory condition affecting the gastrointestinal (GI) tract. The study aims to evaluate microbiome profiles (bacteriome, and mycobiome) across three different sample types (fecal, intestinal washings, and intestinal epithelial biopsies) in a cohort of adult patients with Crohn's disease (CD) living in British Columbia, Canada, and investigate whether a microbial signature may predict response to IBD therapy. Aims: 1. Determine microbiome signatures, across different sample types, in quiescent and active disease for patients with CD living in BC, Canada. 2. Evaluate whether fecal, mucosal, and/or intestinal epithelial biopsy microbiome signatures can predict response to therapy. Methods Study Design: Phase 1: A cross-sectional pilot study to evaluate the microbiome in patients with IBD (with active and quiescent disease) and in non-IBD controls. Primary Outcome: Compare results of microbial analyses (including bacteriome and mycobiome) across three different sample types: intestinal washings and intestinal epithelial biopsy specimens taken during colonoscopy, as well as fecal samples. Secondary Outcomes: Investigate correlations between the microbial analyses across different sample types and disease activity in CD. Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients. Investigate if fecal microbiome composition and function 2 weeks after bowel preparation is comparable to pre-bowel preparation fecal microbiome in a subset of patients with CD. Phase 2: A longitudinal observational study with a 12-month follow-up. Primary Outcome: Identify if there are any microbial signatures that predict response to therapy in patients with active disease requiring escalated therapy, assessed clinically and biochemically after induction (12-16 weeks) and at 12 months (+/- 3 months). Secondary Outcomes: Compare the sensitivity and specificity of microbial analyses from each sample type in predicting response to therapy.
研究者
Genelle Lunken
Assistant Professor
University of British Columbia
入排标准
入选标准
- •CD patients:
- •Adult patients ≥19 years old and ≤ 80 years old.
- •CD with distal small bowel and/or colonic involvement that is endoscopically assessable with colonoscopy.
- •Undergoing colonoscopy as part of routine clinical care.
- •Active or quiescent disease.
- •Active disease will be defined as a simple endoscopic score for CD (SES-CD).
- •Quiescent disease is defined as an SES-CD \<
- •Mild active disease will be defined as a SES-CD of 3-6, or 3 with isolated ileal CD.
- •Moderate/severe active disease will be defined as a simple endoscopic score for CD (SES-CD) ≥ 7 or ≥ 4 for isolated ileal CD.
- •Non-IBD controls:
排除标准
- •CD patients:
- •Active perianal CD - defined as collection on MRI or clinically active fistula (i.e., draining fistula).
- •Proximal small bowel (defined as not endoscopically assessable by colonoscopy) or isolated upper GI CD.
- •Colectomy or Proctocolectomy.
- •Pouch, J-Pouch or Reversed pouch surgery.
- •Short Bowel Syndrome (SBS) diagnosis.
- •Antibiotics in the last 2 months for any indication.
- •Gastroenteritis or travel outside of Canada and the United States in the last month.
- •Colorectal cancer, high-grade dysplasia or a polyp ≥2cm diagnosed at baseline endoscopy.
- •Pregnant or breastfeeding.
结局指标
主要结局
Compare results of microbial analyses (including bacteriome and mycobiome) across three different sample types: intestinal washings and intestinal epithelial biopsy specimens taken during colonoscopy as well as fecal samples.
时间窗: 24 months
Microbial analyses that will be undertaken for each sample type are as follows: Stool: * Metagenomics (Shotgun sequencing, ITS sequencing for fungal analysis) * Metaproteomics and metabolomics (Host, microbial, and dietary protein analysis, microbial metabolite analysis) * Anaerobic culturing (Simulate gut environment, use dietary substrates to target key microbes) Biopsy specimens: * Organoid culturing (In vitro gut model analysis, epithelial-microbiome analysis, mucin production analysis) * RNA-seq, transcriptomics (Gene expression profiling analysis, disease marker identification) * Metagenomics * Metaproteomics and metabolomics Intestinal washings: * Mucin analysis (Glycoprotein analysis) * Metagenomics * Metaproteomics and metabolomics
In patients with active Crohn's disease, where a decision is made to escalate therapy after the index endoscopy, identify if there are any microbial signatures that predict response to therapy after induction (12 - 16 weeks).
时间窗: 24 months
* Clinical Response: Defined based on changes in clinical symptoms as per standardized clinical scoring systems (SES-CD). * Biochemical Response: Assessed through C-reactive protein (CRP) levels and fecal calprotectin, two biomarkers that indicate inflammation or disease activity. The Simple Endoscopy Score for Crohn's Disease (SES-CD) is an objective clinical assessment of the severity of a patient's Crohn's disease. A higher score means more severe disease activity. The three severity classes of SES-CD scoring are as follows: * Endoscopic remission (SES-CD \<3). * Moderate to severe endoscopically active disease (SES-CD ≥7 or ≥4 for isolated ileal CD and at least one large ulcer (≥5mm)). * Mild endoscopically active disease (SES-CD of 3-6, or 3 with isolated ileal CD, with no large ulcers).
In patients with active Crohn's disease, where a decision is made to escalate therapy after the index endoscopy, identify if there are any microbial signatures that predict sustained response to therapy at 12 Months (+/- 3 months).
时间窗: 24 months
* Clinical Response: Continuation or improvement in clinical symptoms as measured by standardized clinical scoring systems (SES-CD). * Biochemical Response: Persistent normalization or improvement in CRP levels and fecal calprotectin. * Endoscopic Response: Improvement or healing of mucosal lesions as observed during endoscopic examination, assessed by validated clinical scoring systems (SES-CD).
次要结局
- Investigate the correlations between the microbial analyses across different sample types and disease activity in CD.(24 months)
- Compare the difference in microbial analyses within each sample type between active and quiescent CD as well as non-IBD patients.(24 months)
- Investigate, in a subset of patients with CD, if fecal microbiome composition and function 2 weeks after bowel preparation is comparable to pre-bowel preparation fecal microbiome.(24 months)
- Compare the sensitivity of the microbial analyses from each sample type in their prediction of response to therapy.(24 months)
- Compare the specificity of the microbial analyses from each sample type in their prediction of response to therapy.(24 months)