Effect of Serotonergic Stimulation on the Gut-brain Axis

NCT03920410 | Active Not Recruiting

• 1 other identifier: 5HT
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Selective serotonin reuptake inhibitors increase the level of serotonin. This study will use functional magnetic resonance imaging to examine how subjects with, and without, irritable bowel syndrome patients respond to serotonergic stimulation. Brain activation during emotional and arithmetic tasks and during visceral pain will be measured after serotonergic stimulation using the oral administration of Escitalopram (10 mg). The investigators will further integrate background parameters of the irritable bowel syndrome subjects and healthy controls (such as microbiota composition, genetic markers of serotonergic and inflammatory pathways, intestinal permeability, state of mood and visceral sensitivity) with the responses to the various challenges on the level of functional brain imaging. These responses may reveal a 'footprint' of the individual gut-brain axis function. Analyses of these individual footprints in multiple subjects with and without irritable bowel syndrome may reveal biosignatures characterising certain groups of patients according to specific gut-brain signalling response patterns. These biosignatures may be used to develop an individualised treatment algorithm for irritable bowel syndrome therapy.

Conditions

Healthy; Irritable Bowel Syndrome

Outcome Measures

Primary Outcomes (1)

• Differences in functional brain response pattern to the barostat in stimulated compared to unstimulated serotonergic activity

  functional magnetic resonance imaging

  1 week

Secondary Outcomes (5)

• Differences in functional brain response pattern to the Montreal Imaging Stress Task between stimulated and unstimulated serotonergic activity

  1 week

• Differences in functional brain response pattern to the Emotional Attention Task between stimulated and unstimulated serotonergic activity

  1 week

• Differences in functional brain response pattern to the barostat stimulus paradigm between irritable bowel syndrome patients and healthy controls for stimulated and unstimulated serotonergic activity

  1 week

• Differences in functional brain response pattern to the Montreal imaging stress task (MIST) between irritable bowel syndrome patients and healthy controls for stimulated and unstimulated serotonergic activity

  1 week

• Differences in functional brain response pattern to the emotional attention task (EAT) between irritable bowel syndrome patients and healthy controls for stimulated and unstimulated serotonergic activity

  1 week

Study Arms (2)

stimulated serotonergic activity

EXPERIMENTAL

Other: serotonergic stimulation

unstimulated serotonergic activity

EXPERIMENTAL

Other: no serotonergic stimulation

Interventions

serotonergic stimulation OTHER

Increase of serotonergic activity by a single oral administration of 10 mg Escitalopram, a Selective Serotonin Reuptake Inhibitor (SSRI), packed in a coloured hydroxypropylmethylcellulose capsule.

stimulated serotonergic activity

no serotonergic stimulation OTHER

Oral administration of a placebo. The placebo will consist of a coloured hydroxypropylmethylcellulose capsule filled with microcrystalline cellulose.

unstimulated serotonergic activity

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects fulfill Rome IV diagnostic criteria for irritable bowel syndrome and pain frequency for at least 1 day per week in the last 12 weeks
• Males or females aged 18-65 years
• Signed informed consent

You may not qualify if:

• Concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (\< 12 weeks), antibiotics (\< 12 weeks)
• Concurrent or recent (\< 4 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St. John´s Wort and probiotics)
• Diagnosis of major psychiatric or somatic disease other than part of irritable bowel syndrome
• Suicidal tendencies according to Montgomery Åsberg Depression Ratings Scale and/or clinical judgment
• Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test, and/or clinical judgment
• Recent (\< 4 weeks) intake of proton pump inhibitors (e.g., omeprazole)
• Epilepsy
• Cerebral bleeding or history of cerebral bleeding
• Pregnancy or breastfeeding (will be asked)
• Claustrophobia
• Smoking or using tobacco including snuff
• Dominant left-hand
• Medical implant (e.g., pacemaker)
• Aneurysm clips in the head
• Shunts in the head

Sponsors & Collaborators

• Örebro University, Sweden: lead
• Region Örebro County: collaborator

Study Sites (1)

Örebro University, Region Örebro County

Örebro, 70182, Sweden

Location

MeSH Terms

Conditions

Irritable Bowel Syndrome

Condition Hierarchy (Ancestors)

Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Study Officials

• Robert Brummer, Prof.

  Örebro University, Region Örebro County

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2019
• First Posted: April 18, 2019
• Study Start: April 24, 2019
• Primary Completion: March 31, 2022
• Study Completion: December 1, 2025
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)