Investigating Serotonin Signalling in IBD Patients

Inflammatory Bowel Disease Clinical Trial

— IBD  

Official title:

Investigating Serotonin Signalling in IBD Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01650311
• Other study ID #: 12-239
• Status: Recruiting
• Start date: July 2012
• Est. completion date: May 2025

Study information

• Verified date: October 2023
• Source: McMaster University
• Contact: Jensine Grondin, MSc.
• Phone: 905-525-9140
• Email: grondij[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 85 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases

Locations

Country	Name	City	State
Canada	McMaster University Medical Center	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Country where clinical trial is conducted

Canada, 

References & Publications (38)

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* Note: There are 38 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TPH1	Levels of the gene expression and/or protein quantifications of the enzyme Tph1 will be measured to assess production of 5HT.	At the time of sample collection
Secondary	Receptor expressions	Levels of the various serotonin receptors will be measured to assess changes in serotonin signaling	At the time of sample collection