Irritable Bowel SyndromePhase 3NCT04612803
Antihistamines in the Treatment of Irritable Bowel Syndrome With Diarrhea
A Phase 3 study testing Antihistamine in people with Irritable Bowel Syndrome and Dermatographism, run by University of Cincinnati at 1 site in United States.
Trial 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]. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Irritable Bowel Syndrome, Dermatographism, Post-prandial Diarrhea
- What is being tested?
- Antihistamine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2020to 31 Aug 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- No colonoscopy performed
- GI malabsorption
- Current pregnancy
- Current severe depression or history of psychosis
- Current treatment with tricyclic antidepressants
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Antihistamines in the Treatment of Irritable Bowel Syndrome With Diarrhea: a Cross-Over Trial
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.
Read the 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
- Being tested
- Antihistamine, Placebo
- Keywords
- IBS, irritable bowel syndrome, Dermatographism, post-prandial diarrhea, antihistamine
- Medical subject headings
- Irritable Bowel Syndrome, Familial dermographism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AntihistamineDrug
Also called zyrtec, pepcid
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
PlaceboDrug
These medications will be pre-packaged by the UC Health pharmacy in a manner that results in a double-blinded cross-over design.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
| Intervention Arm | Active comparator | 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. Receives: Drug: Antihistamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
IBS symptomy severity score
≥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.
Measured: 135 days
Secondary outcomes (1)
IBS quality of life
≥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.
Measured: 135 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2020
- Study start1 Feb 2020
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2026
Why it stopped: no funding for clinical research space
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Bernstein, University of Cincinnati
- Investigators
- David Bernstein, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04612803
- Sponsor's protocol ID
- 2020-0193
- Status last verified
- Sep 2026
- First submitted
- 28 Oct 2020
- Last updated
- 4 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan on sharing individual participant data.
Publications
Functional Gastrointestinal Disorders and the Rome IV process. In: Drossman DA, Chang L, Chey WD, Kellow J, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders: disorders of gut-brain interaction.
Hassoun Y, Stevenson MR, Bernstein DI. Idiopathic postprandial diarrhea responsive to antihistamines. Ann Allergy Asthma Immunol. 2019 Oct;123(4):407-409. doi: 10.1016/j.anai.2019.06.022. Epub 2019 Jul 3. No abstract available.
PubMed 31279076Mlynek A, Vieira dos Santos R, Ardelean E, Weller K, Magerl M, Church MK, Maurer M. A novel, simple, validated and reproducible instrument for assessing provocation threshold levels in patients with symptomatic dermographism. Clin Exp Dermatol. 2013 Jun;38(4):360-6; quiz 366. doi: 10.1111/ced.12107.
PubMed 23621090Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci. 1998 Feb;43(2):400-11. doi: 10.1023/a:1018831127942.
PubMed 9512138McHugh KR, Swamy GK, Hernandez AF. Engaging patients throughout the health system: A landscape analysis of cold-call policies and recommendations for future policy change. J Clin Transl Sci. 2018 Dec;2(6):384-392. doi: 10.1017/cts.2019.1.
PubMed 31402985Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x.
PubMed 9146781Passos MC, Lembo AJ, Conboy LA, Kaptchuk TJ, Kelly JM, Quilty MT, Kerr CE, Jacobson EE, Hu R, Friedlander E, Drossman DA. Adequate relief in a treatment trial with IBS patients: a prospective assessment. Am J Gastroenterol. 2009 Apr;104(4):912-9. doi: 10.1038/ajg.2009.13. Epub 2009 Mar 17.
PubMed 19293784Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Dig Dis Sci. 2003 Jul;48(7):1317-23. doi: 10.1023/a:1024159226274.
PubMed 12870789B O'Neil, Some useful moment results in sampling problems. American Statistician Volume 69, Issue 4, 2014
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antihistamines in the Treatment of Irritable Bowel Syndrome With Diarrhea: a Cross-Over Trial
- ClinicalTrials.gov ID
- NCT04612803
- Acronym / sponsor ID
- 2020-0193
- Keywords
- IBS, irritable bowel syndrome, Dermatographism, post-prandial diarrhea, antihistamine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no funding for clinical research space
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2026 (actual)
- First posted
- 3 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboA 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. |
| Intervention Arm | Active comparator | Drug: AntihistamineA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AntihistamineAlso: zyrtec, pepcidCetirizine 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 | Drug | Intervention Arm |
| PlaceboThese medications will be pre-packaged by the UC Health pharmacy in a manner that results in a double-blinded cross-over design. | Drug | Placebo |
Primary outcome
IBS symptomy severity score
Time frame: 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.
1 secondary outcome
IBS quality of life
Time frame: 135 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- BackgroundFunctional Gastrointestinal Disorders and the Rome IV process. In: Drossman DA, Chang L, Chey WD, Kellow J, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders: disorders of gut-brain interaction.
- Background: PubMed 31279076Hassoun Y, Stevenson MR, Bernstein DI. Idiopathic postprandial diarrhea responsive to antihistamines. Ann Allergy Asthma Immunol. 2019 Oct;123(4):407-409. doi: 10.1016/j.anai.2019.06.022. Epub 2019 Jul 3. No abstract available.
- Background: PubMed 23621090Mlynek A, Vieira dos Santos R, Ardelean E, Weller K, Magerl M, Church MK, Maurer M. A novel, simple, validated and reproducible instrument for assessing provocation threshold levels in patients with symptomatic dermographism. Clin Exp Dermatol. 2013 Jun;38(4):360-6; quiz 366. doi: 10.1111/ced.12107.
- Background: PubMed 9512138Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci. 1998 Feb;43(2):400-11. doi: 10.1023/a:1018831127942.
- Background: PubMed 31402985McHugh KR, Swamy GK, Hernandez AF. Engaging patients throughout the health system: A landscape analysis of cold-call policies and recommendations for future policy change. J Clin Transl Sci. 2018 Dec;2(6):384-392. doi: 10.1017/cts.2019.1.
- Background: PubMed 9146781Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997 Apr;11(2):395-402. doi: 10.1046/j.1365-2036.1997.142318000.x.
- Background: PubMed 19293784Passos MC, Lembo AJ, Conboy LA, Kaptchuk TJ, Kelly JM, Quilty MT, Kerr CE, Jacobson EE, Hu R, Friedlander E, Drossman DA. Adequate relief in a treatment trial with IBS patients: a prospective assessment. Am J Gastroenterol. 2009 Apr;104(4):912-9. doi: 10.1038/ajg.2009.13. Epub 2009 Mar 17.
- Background: PubMed 12870789Gordon S, Ameen V, Bagby B, Shahan B, Jhingran P, Carter E. Validation of irritable bowel syndrome Global Improvement Scale: an integrated symptom end point for assessing treatment efficacy. Dig Dis Sci. 2003 Jul;48(7):1317-23. doi: 10.1023/a:1024159226274.
- BackgroundB O'Neil, Some useful moment results in sampling problems. American Statistician Volume 69, Issue 4, 2014
- Individual participant dataSharing planned: No. We do not plan on sharing individual participant data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Bernstein, MD principal investigator
University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Antihistamine in people with Irritable Bowel Syndrome and Dermatographism, run by University of Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
IBS symptomy severity score (time frame: 135 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04612803, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.