Clinical trial NCT01650311: Investigating Serotonin Signalling in IBD Patients
Official title: Investigating Serotonin Signalling in IBD Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Inflammatory Bowel Disease
Keywords: IBD, CD, UC, Serotonin, 5-HT
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2012-07-26
Enrollment: 60
Sex: ALL
Minimum age (years): 19
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: TPH1
timeFrame: At the time of sample collection
Secondary outcomes:
measure: Receptor expressions
timeFrame: At the time of sample collection
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
Study officials:
affiliation: Dept. of Pathology & Molecular Medicine, McMaster University, Hamilton, Canada.
name: Waliul I Khan, MBBS, PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Medicine, McMaster University, Hamilton, Canada.
name: John Marshall, MD, MSc, FRCPC, AGAF.
role: PRINCIPAL_INVESTIGATOR
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