Antihistamines in the Treatment of Irritable Bowel Syndrome With Diarrhea: a Cross-Over Trial
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- IBS symptomy severity score
研究概览
简要总结
Irritable bowel syndrome is a functional disorder of the gastrointestinal tract diagnosed with the Rome criteria. The Rome IV criteria are based on abdominal pain symptoms and stool habits including stool frequency and stool forms [1]. They define 3 main subtypes based on symptoms: 1) IBS with diarrhea; 2) IBS with constipation: and 3) mixed symptoms of constipation and diarrhea. The IBS with diarrhea (IBS-D) subtype has the highest prevalence. Currently, treatment of IBS-D includes antidiarrheals, bile acid sequestrants, antispasmodics, tricyclic antidepressants, and FODMAP diet. However, many patients are intolerant or unresponsive to the above treatments. Outside of IBS, chronic diarrhea affects about 5% of adults. We have described a syndrome in a subset of IBS patients presenting with post prandial diarrhea, flushing and dermatographia whose symptoms are prevented by pre-treatment with combined H1 and H2 antihistamines [2]. However, the prevalence of this syndrome among the IBS + D patients is not known nor have the clinical characteristics or predictors of antihistamine responsive IBS + D been defined.
详细描述
We have published a series of 5 patients with chronic post prandial diarrhea (PPD) that begins within 3 hours after eating, associated with dermatographia, responsive to antihistamines [2]. In these cases, no underlying causes were identified to explain PPD; diagnoses of food allergy, lactose intolerance, celiac disease, dumping syndromes, inflammatory bowel disease, systemic mastocytosis were excluded. Patients with the syndrome have prior histories of chronic urticaria and experience associated transient symptoms of flushing, headache, tachycardia, and abdominal bloating during PPD episodes.
This syndrome, except for our published report, have not been previously described in the medical literature. Patients with systemic mastocytosis and mast cell activation syndrome experience PPD but along with anaphylactic manifestations (e.g. wheezing, hypotension) and measurable mast cell biomarkers are identifiable in affected patients (i.e. serum mast cell tryptase or 24 hour urine methylhistamine, PGF2a). Therefore, it is important to characterize PPD responsive to antihistamines in a general GI patient population and to publish our findings. The impact on human health will be substantial; we found that these patients are undiagnosed and untreated for many years.
Our aim is to recruit a minimum of 29 (with a maximum of 50) patients from community (third-party) and the UC Health affiliated primary care, allergy and/or gastroenterology clinics and the Bernstein Allergy Group David Bernstein MD, a faculty member in the Division of Immunology, Rheumatology, and Allergy, Yashu Dhamija MD (faculty), allergy fellows and GI fellows will direct and implement subject screening and consenting
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Thus, the trial medication package may contain 168 total placebo meds or 56 encapsulated famotidine and 56 encapsulated cetirizine. These medications will be pre-packaged by the UC Health pharmacy in a manner that results in a double-blinded cross-over design.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years and older
- •Prior to Diagnosis of IBS + diarrhea based on ICD 10 codes with or without constipation unresponsive to prior treatments
- •Moderate to severe symptom severity score (>175 points) based on IBS symptom severity scale
- •Seeking evaluation by a health care professional
- •Negative serologic celiac panel
- •No response to lactose elimination diet by history
- •Normal colonoscopy
- •Able to complete symptoms diaries and global evaluations
排除标准
- •Confirmed IgE dependent food allergy as a cause of the gastrointestinal symptoms.
- •Lactose intolerance by history
- •Celiac disease by serology
- •Inflammatory bowel disease or colitis
- •Bile acid diarrhea by history
- •Post-surgical GI symptoms (e.g., dumping syndrome) by history
- •No colonoscopy performed
- •GI malabsorption
- •Current pregnancy
- •Current severe depression or history of psychosis
- •Current treatment with tricyclic antidepressants
研究组 & 干预措施
Placebo
A package containing two bottles of encapsulated placebos. The patient will be instructed to take 1 tab of placebo A twice a day and 1 tab of placebo B twice a day for 28 days.
干预措施: Placebo (Drug)
Intervention Arm
A package containing two bottles each with an active medication including encapsulated cetirizine or famotidine. The patient will be instructed to take 10 mg of cetirizine twice a day and 20 mg of famotidine twice a day for 28 days.
干预措施: Antihistamine (Drug)
结局指标
主要结局
IBS symptomy severity score
时间窗: 135 days
≥50 point in reduction of symptoms with antihistamines based on the IBS symptom severity scale (IBS-SSS). This validated scale contains 5 questions that measures on a 100 point scale (for a total of 500 points) the severity of abdominal pain, frequency of abdominal pain, severity of abdominal distension, dissatisfaction with bowel habits, and interference with quality of life.
次要结局
- IBS quality of life(135 days)
研究者
David Bernstein
Emeritus Professor of Medicine
University of Cincinnati