Inflammatory Bowel DiseaseIBDNCT01650311
Investigating Serotonin Signalling in IBD Patients
An observational study of Inflammatory Bowel Disease, run by McMaster University at 1 site in Canada.
Trial summary
Alterations in normal serotonin (5-hydroxytryptamine;5-HT) signaling have been reported in ulcerative colitis (UC) and Crohn's disease (CD). Studies report an increase in enterochromaffin (EC) cell, main source of 5-HT in the gut, numbers in CD and UC patients. Read more about this study
- Who is it for?
- Ages 19 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Bowel Disease
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2012to Nov 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 19 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: All potential participants will be included only if they meet the stringent inclusion criteria in place. Only when their eligibility is confirmed the potential participants will be approached for consent prior to endoscopy. For healthy subjects, they will be screened and consented from the colorectal screening list, also prior to endoscopy.
Who may be able to join
- Patient groups: Disease diagnosis (CD or UC),duration of disease, previous/type of treatments, duration of treatment and disease prognosis.
- Healthy controls: No diagnosis of CD or UC and no diagnosis of IBS.
Who cannot join
- Patient groups: Drugs that directly affect components of 5-HT signaling, any other disease or condition that may interfere with study assessments as judged by the investigator.
- Healthy controls:Chronic use of any anti-inflammatory drugs, drugs that directly affect components of 5-HT signalling and any other disease or condition that may interfere with study assessments as judged by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
McMaster University Medical Center
Hamilton, Ontario, L8S 4K1
About this study
Alterations in normal serotonin (5-hydroxytryptamine;5-HT) signaling have been reported in ulcerative colitis (UC) and Crohn's disease (CD). Studies report an increase in enterochromaffin (EC) cell, main source of 5-HT in the gut, numbers in CD and UC patients. Up-regulated expression of mucosal Tryptophan hydroxylase (TPH)-1, catalytic enzyme in 5-HT production, messenger RNA (mRNA) have been found in CD patients in remission who are suffering the irritable bowel syndrome (IBS)-like symptoms. Alterations in normal 5-HT signaling has also been reported in animal models of inflammatory bowel disease (IBD). Thus, the aim of the proposed research project will be to study the alterations in 5-HT signalling accompanying GI inflammatory conditions, such as IBD.
Read the detailed description
The gut produces approximately 95% of serotonin (5-hydroxytryptamine; 5-HT) found in the human body; where, it is a very important mucosal signaling molecule participating in gut motility, sensation, and secretion.The vast majority of the gut-derived 5-HT is produced by specialized epithelial cells of The GI tract, called enterochromaffin (EC) cells. EC cells produce 5-HT from dietary tryptophan, this process involves the rate limiting enzyme tryptophan hydroxylase (TPH) 1, once produced this 5-HT can be released into the gut lumen, surrounding tissue and can enter the blood circulation.5-HT mediates many gastrointestinal functions, including secretion and peristalsis, by acting on a diverse range of 5-HT receptors. Five of the seven known receptor families of 5-HT (5-HT1, 5-HT2, 5-HT3, 5-HT4 and 5-HT7) are expressed in the gut.
5-HT has been evaluated in IBD and in animal models of colitis. An increase in numbers of EC cells expressing 5-HT is observed in CD and UC patients and consumption of selective 5-HT reuptake inhibitors is associated with microscopic colitis. In the present study, we plan to investigate the key elements of mucosal 5-HT signaling in CD patients for a better understanding of the role of 5-HT in pathogenesis of IBD.
- Conditions
- Inflammatory Bowel Disease
- Keywords
- IBD, CD, UC, Serotonin, 5-HT
- Medical subject headings
- Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Healthy control group will include participants consenting prior to colorectal cancer screening. | |
| CD patient groups | The patient groups will include patients with clinical diagnosis of CD. | |
| UC patient group | The patient groups will include patients with clinical diagnosis of UC. |
What is being measured
The primary outcome is the main question the study is designed to answer.
TPH1
Levels of the gene expression and/or protein quantifications of the enzyme Tph1 will be measured to assess production of 5HT.
Measured: At the time of sample collection
Secondary outcomes (1)
Receptor expressions
Levels of the various serotonin receptors will be measured to assess changes in serotonin signaling
Measured: At the time of sample collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionNov 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for Inflammatory Bowel DiseaseStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Waliul I Khan, MBBS, PhD., Principal investigator, Dept. of Pathology & Molecular Medicine, McMaster University, Hamilton, Canada.John Marshall, MD, MSc, FRCPC, AGAF., Principal investigator, Department of Medicine, McMaster University, Hamilton, Canada.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01650311
- Sponsor's protocol ID
- 12-239
- Acronym
- IBD
- Status last verified
- Oct 2026
- First submitted
- 17 Jun 2012
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, Crowell MD, Sharkey KA, Gershon MD, Mawe GM, Moses PL. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64. doi: 10.1053/j.gastro.2004.03.013.
PubMed 15188158Minderhoud IM, Oldenburg B, Schipper ME, ter Linde JJ, Samsom M. Serotonin synthesis and uptake in symptomatic patients with Crohn's disease in remission. Clin Gastroenterol Hepatol. 2007 Jun;5(6):714-20. doi: 10.1016/j.cgh.2007.02.013. Epub 2007 May 4.
PubMed 17481962El-Salhy M, Danielsson A, Stenling R, Grimelius L. Colonic endocrine cells in inflammatory bowel disease. J Intern Med. 1997 Nov;242(5):413-9. doi: 10.1046/j.1365-2796.1997.00237.x.
PubMed 9408072Sharkey KA, Mawe GM. Neuroimmune and epithelial interactions in intestinal inflammation. Curr Opin Pharmacol. 2002 Dec;2(6):669-77. doi: 10.1016/s1471-4892(02)00215-1.
PubMed 12482729Khan WI, Ghia JE. Gut hormones: emerging role in immune activation and inflammation. Clin Exp Immunol. 2010 Jul 1;161(1):19-27. doi: 10.1111/j.1365-2249.2010.04150.x. Epub 2010 Apr 9.
PubMed 20408856Buchan AM. Nutrient Tasting and Signaling Mechanisms in the Gut III. Endocrine cell recognition of luminal nutrients. Am J Physiol. 1999 Dec;277(6):G1103-7. doi: 10.1152/ajpgi.1999.277.6.G1103.
PubMed 10600808Rindi G, Kloppel G. Endocrine tumors of the gut and pancreas tumor biology and classification. Neuroendocrinology. 2004;80 Suppl 1:12-5. doi: 10.1159/000080733.
PubMed 15477709Gordon JI, Schmidt GH, Roth KA. Studies of intestinal stem cells using normal, chimeric, and transgenic mice. FASEB J. 1992 Sep;6(12):3039-50. doi: 10.1096/fasebj.6.12.1521737.
PubMed 1521737Lomax AE, Linden DR, Mawe GM, Sharkey KA. Effects of gastrointestinal inflammation on enteroendocrine cells and enteric neural reflex circuits. Auton Neurosci. 2006 Jun 30;126-127:250-7. doi: 10.1016/j.autneu.2006.02.015. Epub 2006 Apr 17.
PubMed 16616704Nagata K, Fujimiya M, Sugiura H, Uehara M. Intracellular localization of serotonin in mast cells of the colon in normal and colitis rats. Histochem J. 2001 Sep-Oct;33(9-10):559-68. doi: 10.1023/a:1014960026247.
PubMed 12005028Bertrand PP, Bertrand RL. Serotonin release and uptake in the gastrointestinal tract. Auton Neurosci. 2010 Feb 16;153(1-2):47-57. doi: 10.1016/j.autneu.2009.08.002. Epub 2009 Sep 2.
PubMed 19729349Spiller R. Serotonin and GI clinical disorders. Neuropharmacology. 2008 Nov;55(6):1072-80. doi: 10.1016/j.neuropharm.2008.07.016. Epub 2008 Jul 19.
PubMed 18687345Belai A, Boulos PB, Robson T, Burnstock G. Neurochemical coding in the small intestine of patients with Crohn's disease. Gut. 1997 Jun;40(6):767-74. doi: 10.1136/gut.40.6.767.
PubMed 9245931Wheatcroft J, Wakelin D, Smith A, Mahoney CR, Mawe G, Spiller R. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction. Neurogastroenterol Motil. 2005 Dec;17(6):863-70. doi: 10.1111/j.1365-2982.2005.00719.x.
PubMed 16336502Gershon MD. Serotonin and its implication for the management of irritable bowel syndrome. Rev Gastroenterol Disord. 2003;3 Suppl 2:S25-34.
PubMed 12776000
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating Serotonin Signalling in IBD Patients
- ClinicalTrials.gov ID
- NCT01650311
- Acronym / sponsor ID
- IBD / 12-239
- Conditions
- Inflammatory Bowel Disease
- Keywords
- IBD, CD, UC, Serotonin, 5-HT
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 26 Jul 2012 (estimated)
- 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.
Alterations in normal serotonin (5-hydroxytryptamine;5-HT) signaling have been reported in ulcerative colitis (UC) and Crohn's disease (CD). Studies report an increase in enterochromaffin (EC) cell, main source of 5-HT in the gut, numbers in CD and UC patients. Up-regulated expression of mucosal Tryptophan hydroxylase (TPH)-1, catalytic enzyme in 5-HT production, messenger RNA (mRNA) have been found in CD patients in remission who are suffering the irritable bowel syndrome (IBS)-like symptoms. Alterations in normal 5-HT signaling has also been reported in animal models of inflammatory bowel disease (IBD). Thus, the aim of the proposed research project will be to study the alterations in 5-HT signalling accompanying GI inflammatory conditions, such as IBD.
Detailed description
The gut produces approximately 95% of serotonin (5-hydroxytryptamine; 5-HT) found in the human body; where, it is a very important mucosal signaling molecule participating in gut motility, sensation, and secretion.The vast majority of the gut-derived 5-HT is produced by specialized epithelial cells of The GI tract, called enterochromaffin (EC) cells. EC cells produce 5-HT from dietary tryptophan, this process involves the rate limiting enzyme tryptophan hydroxylase (TPH) 1, once produced this 5-HT can be released into the gut lumen, surrounding tissue and can enter the blood circulation.5-HT mediates many gastrointestinal functions, including secretion and peristalsis, by acting on a diverse range of 5-HT receptors. Five of the seven known receptor families of 5-HT (5-HT1, 5-HT2, 5-HT3, 5-HT4 and 5-HT7) are expressed in the gut.
5-HT has been evaluated in IBD and in animal models of colitis. An increase in numbers of EC cells expressing 5-HT is observed in CD and UC patients and consumption of selective 5-HT reuptake inhibitors is associated with microscopic colitis. In the present study, we plan to investigate the key elements of mucosal 5-HT signaling in CD patients for a better understanding of the role of 5-HT in pathogenesis of IBD.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | – | –Healthy control group will include participants consenting prior to colorectal cancer screening. |
| CD patient groups | – | –The patient groups will include patients with clinical diagnosis of CD. |
| UC patient group | – | –The patient groups will include patients with clinical diagnosis of UC. |
Who may qualify
- Ages
- 19 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- All potential participants will be included only if they meet the stringent inclusion criteria in place. Only when their eligibility is confirmed the potential participants will be approached for consent prior to endoscopy. For healthy subjects, they will be screened and consented from the colorectal screening list, also prior to endoscopy.
Key inclusion criteria (2 listed)
- Patient groups: Disease diagnosis (CD or UC),duration of disease, previous/type of treatments, duration of treatment and disease prognosis.
- Healthy controls: No diagnosis of CD or UC and no diagnosis of IBS.
Key exclusion criteria (2 listed)
- Patient groups: Drugs that directly affect components of 5-HT signaling, any other disease or condition that may interfere with study assessments as judged by the investigator.
- Healthy controls:Chronic use of any anti-inflammatory drugs, drugs that directly affect components of 5-HT signalling and any other disease or condition that may interfere with study assessments as judged by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
TPH1
Time frame: At the time of sample collection
Levels of the gene expression and/or protein quantifications of the enzyme Tph1 will be measured to assess production of 5HT.
1 secondary outcome
Receptor expressions
Time frame: At the time of sample collection
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2026.
- Background: PubMed 15188158Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, Crowell MD, Sharkey KA, Gershon MD, Mawe GM, Moses PL. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64. doi: 10.1053/j.gastro.2004.03.013.
- Background: PubMed 17481962Minderhoud IM, Oldenburg B, Schipper ME, ter Linde JJ, Samsom M. Serotonin synthesis and uptake in symptomatic patients with Crohn's disease in remission. Clin Gastroenterol Hepatol. 2007 Jun;5(6):714-20. doi: 10.1016/j.cgh.2007.02.013. Epub 2007 May 4.
- Background: PubMed 9408072El-Salhy M, Danielsson A, Stenling R, Grimelius L. Colonic endocrine cells in inflammatory bowel disease. J Intern Med. 1997 Nov;242(5):413-9. doi: 10.1046/j.1365-2796.1997.00237.x.
- Background: PubMed 12482729Sharkey KA, Mawe GM. Neuroimmune and epithelial interactions in intestinal inflammation. Curr Opin Pharmacol. 2002 Dec;2(6):669-77. doi: 10.1016/s1471-4892(02)00215-1.
- Background: PubMed 20408856Khan WI, Ghia JE. Gut hormones: emerging role in immune activation and inflammation. Clin Exp Immunol. 2010 Jul 1;161(1):19-27. doi: 10.1111/j.1365-2249.2010.04150.x. Epub 2010 Apr 9.
- Background: PubMed 10600808Buchan AM. Nutrient Tasting and Signaling Mechanisms in the Gut III. Endocrine cell recognition of luminal nutrients. Am J Physiol. 1999 Dec;277(6):G1103-7. doi: 10.1152/ajpgi.1999.277.6.G1103.
- Background: PubMed 15477709Rindi G, Kloppel G. Endocrine tumors of the gut and pancreas tumor biology and classification. Neuroendocrinology. 2004;80 Suppl 1:12-5. doi: 10.1159/000080733.
- Background: PubMed 1521737Gordon JI, Schmidt GH, Roth KA. Studies of intestinal stem cells using normal, chimeric, and transgenic mice. FASEB J. 1992 Sep;6(12):3039-50. doi: 10.1096/fasebj.6.12.1521737.
- Background: PubMed 16616704Lomax AE, Linden DR, Mawe GM, Sharkey KA. Effects of gastrointestinal inflammation on enteroendocrine cells and enteric neural reflex circuits. Auton Neurosci. 2006 Jun 30;126-127:250-7. doi: 10.1016/j.autneu.2006.02.015. Epub 2006 Apr 17.
- Background: PubMed 12005028Nagata K, Fujimiya M, Sugiura H, Uehara M. Intracellular localization of serotonin in mast cells of the colon in normal and colitis rats. Histochem J. 2001 Sep-Oct;33(9-10):559-68. doi: 10.1023/a:1014960026247.
- Background: PubMed 19729349Bertrand PP, Bertrand RL. Serotonin release and uptake in the gastrointestinal tract. Auton Neurosci. 2010 Feb 16;153(1-2):47-57. doi: 10.1016/j.autneu.2009.08.002. Epub 2009 Sep 2.
- Background: PubMed 18687345Spiller R. Serotonin and GI clinical disorders. Neuropharmacology. 2008 Nov;55(6):1072-80. doi: 10.1016/j.neuropharm.2008.07.016. Epub 2008 Jul 19.
- Individual participant dataSharing planned: No
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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.
Waliul I Khan, MBBS, PhD. principal investigator
Dept. of Pathology & Molecular Medicine, McMaster University, Hamilton, Canada.
John Marshall, MD, MSc, FRCPC, AGAF. principal investigator
Department of Medicine, McMaster University, Hamilton, Canada.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Inflammatory Bowel Disease, run by McMaster University at 1 site in Canada.
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 2 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 9 Oct 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jensine Grondin, MSc. (905-525-9140 ext. 22970, grondij@mcmaster.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TPH1 (time frame: At the time of sample collection). 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 NCT01650311, which also lists 38 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 9 Oct 2026.