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Antihistamines in the Treatment of Irritable Bowel Syndrome With Diarrhea

Antihistamines in the Treatment of Irritable Bowel Syndrome With Diarrhea: a Cross-Over Trial

Status
Withdrawn
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04612803
Enrollment
0
Registered
2020-11-03
Start date
2020-02-01
Completion date
2026-08-31
Last updated
2026-09-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dermatographism, Irritable Bowel Syndrome, Post-prandial Diarrhea

Keywords

IBS, irritable bowel syndrome, Dermatographism, post-prandial diarrhea, antihistamine

Brief summary

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.

Detailed description

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

Interventions

DRUGAntihistamine

Cetirizine 10 mg and famotidine 20 mg will be dispensed to each patient, to be taken twice a day at 6-9AM one hour before eating breakfast and again at evening 12 hours after the morning dose for 30 days

DRUGPlacebo

These medications will be pre-packaged by the UC Health pharmacy in a manner that results in a double-blinded cross-over design.

Sponsors

University of Cincinnati
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Masking description

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.

Intervention model description

Visit 1: subjects explained the details of the study and informed consent. Antihistamines stopped. Subject starts placebo for 10 days. After run-in, subject will present for visit 2 on study day 10. The subject will be randomized to receive either: A package containing encapsulated cetirizine or famotidine. Subject will take 10 mg of cetirizine twice a day and 20 mg of famotidine twice a day for 28 days. OR A package containing two bottles of encapsulated placebos. Subject will take 1 tab of placebo A twice a day and 1 tab of placebo B twice a day for 28 days. Visit 3 Visit 3 study day 38. The subject begins 14-day washout with placebo. Visit 4 Visit 3, on study day 52, the subject presents for bottle recovery and instructions for second intervention phase. The patient will be dispensed their cross-over treatment. Visit 5 Visit 5 will occur on study day 80. The remaining medications will be collected from the subject.

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* 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

Exclusion criteria

* 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

Design outcomes

Primary

MeasureTime frameDescription
IBS symptomy severity score135 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.

Secondary

MeasureTime frameDescription
IBS quality of life135 days≥10 point improvement in Quality of Life (IBS-QOL) questionnaire and a "moderately improved" or "substantially improved" on the IBS global assessment of improvement (IBS-GAI) scale. The IBS-QOL is a 34-item questionnaire which assesses the degree to which IBS interferes with the patient's quality of life. The IBS-GAI asks one question that assesses the overall improvement in symptoms in the past 7 days.

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORDavid Bernstein, MD

University of Cincinnati

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Sep 5, 2026