Investigating Serotonin Signalling in IBD Patients

Recruiting

• Conditions: Inflammatory Bowel Disease

• Registration Number: NCT01650311
• Lead Sponsor: McMaster University

Brief 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. 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 Timeline

• Study First Submitted: 2012-06-17
• Study Start: 2012-07
• Study First Submitted QC: 2012-07-23
• Study First Posted: 2012-07-26
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• 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.

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Exclusion Criteria

• 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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
TPH1	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.

Secondary Outcome Measures

Name	Time	Method
Receptor expressions	At the time of sample collection	Levels of the various serotonin receptors will be measured to assess changes in serotonin signaling

Trial Locations

Locations (1)

McMaster University Medical Center; 🇨🇦 Hamilton, Ontario, Canada