The Role of Fiber in the Prevention and Treatment of Fecal Incontinence
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 2
- 主要终点
- Stool microbiome
研究概览
简要总结
The purpose of this study is to determine the effect of fiber supplementation on the fecal metagenome and metabolome in relation to symptoms and anorectal physiology in post-menopausal women with irritable bowel syndrome with diarrhea suffering from liquid stool fecal incontinence (FI.)
详细描述
This is an open-label, single-arm study at Massachusetts General Hospital that aims to recruit post-menopausal female patients with solid stool fecal incontinence. The investigators hope that subjects taking a daily fiber supplement will experience reduced episodes and symptoms of fecal incontinence, measured through quality of life questionnaires and daily stool and food diaries. Subjects will undergo 2 anorectal manometry procedures. Stool samples will also be collected for metabolomic and metagenomic analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, post-menopausal
- •Age 50-90 years old
- •BMI >18.5 and <40 kg/m2
- •Rome IV criteria for liquid stool fecal incontinence occurring at least twice per month
- •At least one FI episode during the run-in period
- •Compliant with reporting during run-in (completion of two 3-day food diaries and two 7-day bowel diaries)
- •Submission of two stool samples during the run-in period
- •Ability to follow verbal and written instructions
- •Informed consent form signed by the subjects
排除标准
- •Less than two episodes per month of liquid stool fecal incontinence
- •Non-compliance with reporting during run-in
- •Patients reporting laxative, enema, and/or suppository usage during the run-in period
- •GI tract structural abnormality that would increase likelihood of obstruction
- •Dysphagia, swallowing disorder, or history of esophageal structural lesions
- •History of GI lumen surgery within 60 days prior to entry into the study
- •Neurological disorders, metabolic disorders, or other significant disease that would impair their ability to participate in the study
- •Inability to tolerate or contraindication to performance of anorectal manometry
- •Celiac disease, Crohn's disease, ulcerative colitis
- •Current anorectal fistula and/or abscess
- •Age <50 or >90
- •BMI of <18.5 or ≥40 kg/m2
- •History of allergic reaction to psyllium
- •Previous trial of soluble fiber supplementation for fecal incontinence within the previous 30 days
- •History of sacral nerve stimulator or artificial anal sphincter placement
- •Administration of investigational products within 1 month prior to Screening Visit
- •Subjects anticipating surgical intervention during the study
- •19. History of intestinal stricture (e.g., Crohn's disease)
- •History of intestinal obstruction or subjects at high risk of intestinal obstruction including suspected small bowel adhesions
- •History of malabsorption
- •Any other clinically significant disease interfering with the assessments of psyllium, according to the Investigator (e.g., disease requiring corrective treatment, potentially leading to study discontinuation)
- •Any relevant biochemical abnormality interfering with the assessments of psyllium, according to the Investigator
- •Patients with metallic implants within a 30 cm radius of the TAMS electromagnetic coil
- •Currently on opioids
- •Patients with severe cardiac disease, chronic renal failure, or previous GI surgery EXCEPT cholecystectomy, appendectomy, Nissen fundoplication, and partial colectomy
- •Patients with neurological diseases and increased intracranial pressure
- •Patients with impaired cognizance
- •Previous pelvic surgery/radiation, radical hysterectomy
- •Patients with Ulcerative Colitis or Crohn's Disease
- •History of or current rectal prolapse
- •Previous history of anal fissure, anal surgery (abscess), congenital anorectal malformation, fistulae or inflamed hemorrhoids
- •Pregnant women
- •Use of antibiotics in previous 60 days
结局指标
主要结局
Stool microbiome
时间窗: Change from baseline to final visit. Through study completion, up to 6 weeks.
Stool samples will be shipped to Metabolon Inc, for metabolomics profiling on a well-validated high-throughput metabolomics platform. Sample prep and global metabolomics profiling will be conducted using four liquid chromatography tandem mass spectrometry methods that measure four complementary sets of metabolite classes. Metabolite peaks are quantified using area-under-the curve. Raw area counts for each metabolite in each sample are normalized to correct for variation resulting from inter-day tuning differences by setting the medians to 1.0 for each run. Metabolites are identified by automated comparison of the ion features in the experimental samples to a reference library of \~8,000 chemical standard entries that are curated for quality control using Metabolon software. Coefficients of variations (CVs) will be measured in blinded quality control samples randomly distributed among study samples, and we will analyze and control for batch variation.
Stool metagenomics
时间窗: Change from baseline to final visit. Through study completion, up to 6 weeks.
Sequence-based microbial community surveys will be carried out to characterize rare taxa and understand relationships between community membership and function from stool samples collected from baseline to the final visit.
Change in Stool Metagenomics Assessed by Sequence-based Microbial Communities and Rare Taxa
时间窗: Change from baseline to final visit. Through study completion, up to 6 weeks.
The Shannon Diversity Index is a measure of within-sample microbial diversity that incorporates both the number of microbial taxa present (i.e., richness) and the distribution of their relative abundances (i.e., evenness). It is calculated using the relative abundance of observed taxa within each stool sample. Higher values indicate greater microbial diversity. The theoretical minimum value is 0, and there is no fixed theoretical maximum because the upper bound depends on the number of taxa detected in a sample and sequencing depth. In human gut microbiome studies, observed values commonly range from approximately 2 to 6.
Change in Stool Butyrate Abundance Measured by Untargeted LC-MS Metabolomics
时间窗: Change from baseline to final visit. Through study completion, up to 6 weeks.
Butyrate was measured in stool samples using untargeted LC-MS metabolomics performed by Metabolon. Values were batch-normalized by dividing each sample value by the batch-specific median for butyrate, and missing values were imputed using the minimum observed value across batches. The resulting values were log-transformed before analysis. Higher values indicate greater relative abundance of butyrate in stool. Because this measure reflects relative abundance rather than absolute concentration, there is no fixed theoretical range.
次要结局
- Fecal Incontinence quality of life (FIQL)(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Urgency scale(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Anorectal manometry parameters(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Waist circumference measurement (cm)(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Global assessment of relief(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Bloating scale(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Flatus scale(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Fecal incontinence severity index (FISI)(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Translumbosacral anorectal magnetic stimulation(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Fecal Incontinence Severity Assessed by Fecal Incontinence Severity Index (FISI)(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Fecal Incontinence Quality of Life Assessed by Fecal Incontinence Quality of Life (FIQL)(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Anal Squeeze Pressure Assessed by Anorectal Manometry(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Lumbo and Sacral Nerve Latency Assessed by Translumbosacral Anorectal Magnetic Stimulation(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Relief Assessed by the Global Assessment of Relief(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Bloating Scale Assessed by a Bloating Scale(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Urgency Assessed by an Urgency Scale(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Flatus Assessed by a Flatus Scale(Change from baseline to final visit. Through study completion, up to 6 weeks.)
- Change in Waist Circumference Measurement(Change from baseline to final visit. Through study completion, up to 6 weeks.)
研究者
Kyle Staller, MD, MPH
Assistant Professor in Medicine
Massachusetts General Hospital