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Effect of Serotonergic Stimulation on the Gut-brain Axis

Primary Purpose

Healthy, Irritable Bowel Syndrome

Status
Active
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
serotonergic stimulation
no serotonergic stimulation
Sponsored by
Örebro University, Sweden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria for the irritable bowel syndrome group:

  1. 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
  2. Males or females aged 18-65 years
  3. Signed informed consent

Exclusion criteria for the irritable bowel syndrome group:

  1. Concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (< 12 weeks), antibiotics (< 12 weeks)
  2. 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)
  3. Diagnosis of major psychiatric or somatic disease other than part of irritable bowel syndrome
  4. Suicidal tendencies according to Montgomery Åsberg Depression Ratings Scale and/or clinical judgment
  5. Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test, and/or clinical judgment
  6. Recent (< 4 weeks) intake of proton pump inhibitors (e.g., omeprazole)
  7. Epilepsy
  8. Cerebral bleeding or history of cerebral bleeding
  9. Pregnancy or breastfeeding (will be asked)
  10. Claustrophobia
  11. Smoking or using tobacco including snuff
  12. Dominant left-hand
  13. Medical implant (e.g., pacemaker)
  14. Aneurysm clips in the head
  15. Shunts in the head
  16. Grenade-splinter or metal-splinter in the body (e.g., eyes)
  17. Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
  18. Comprehensive tooth-implants or prothesis
  19. Operated in the head
  20. Operated in the heart
  21. Swallowed a video-capsule
  22. Non-corrected astigmatism
  23. Regular intake of antiinflammatory medication (including non-steroidal antiinflammatory drugs)
  24. Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning
  25. Any other reason the investigator feels the subject is not suitable for participation in the study

Inclusion criteria for healthy group:

  1. Males and females aged 18-65 years of age
  2. Signed informed consent

Exclusion criteria for the healthy group:

  1. Concurrent or recent history of gastrointestinal disorders or any somatic disorder
  2. Concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (< 12 weeks), antibiotics (< 12 weeks)
  3. 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)
  4. Concurrent psychiatric or psychological symptomatology defined as above cut-off on Montgomery Åsberg Depression Ratings Scale, above clinical cut-off on hospital anxiety and depression scale (equal to or above 8)
  5. Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test, and/or clinical judgment
  6. Recent (< 4 weeks) intake of proton pump inhibitors, (e.g., omeprazole)
  7. Epilepsy
  8. Cerebral bleeding or history of cerebral bleeding
  9. Pregnancy or breastfeeding (will be asked)
  10. Claustrophobia
  11. Smoking or using tobacco including snuff
  12. Dominant left-hand
  13. Medical implant (e.g., pacemaker)
  14. Aneurysm clips in the head
  15. Shunts in the head
  16. Grenade-splinter or metal-splinter in the body (e.g., eyes)
  17. Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
  18. Comprehensive tooth-implants or prothesis
  19. Operated in the head
  20. Operated in the heart
  21. Swallowed a video-capsule
  22. Non-corrected astigmatism
  23. Intake of anti-inflammatory medication (including non-steroidal antiinflammatory drugs)
  24. Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning
  25. Any other reason the investigator feels the subject is not suitable for participation in the study.

Sites / Locations

  • Örebro University, Region Örebro County

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

stimulated serotonergic activity

unstimulated serotonergic activity

Arm Description

Outcomes

Primary Outcome Measures

Differences in functional brain response pattern to the barostat in stimulated compared to unstimulated serotonergic activity
functional magnetic resonance imaging

Secondary Outcome Measures

Differences in functional brain response pattern to the Montreal Imaging Stress Task between stimulated and unstimulated serotonergic activity
functional magnetic resonance imaging
Differences in functional brain response pattern to the Emotional Attention Task between stimulated and unstimulated serotonergic activity
functional magnetic resonance imaging
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
functional magnetic resonance imaging
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
functional magnetic resonance imaging
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
functional magnetic resonance imaging

Full Information

First Posted
April 12, 2019
Last Updated
March 17, 2023
Sponsor
Örebro University, Sweden
Collaborators
Region Örebro County
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1. Study Identification

Unique Protocol Identification Number
NCT03920410
Brief Title
Effect of Serotonergic Stimulation on the Gut-brain Axis
Official Title
Effect of Serotonergic Stimulation on the Gut-brain Axis in Irritable Bowel Syndrome Patients Compared With Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 24, 2019 (Actual)
Primary Completion Date
March 31, 2022 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Örebro University, Sweden
Collaborators
Region Örebro County

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
In this double-blinded, randomized, cross-over study, irritable bowel syndrome subjects (n = 40) and healthy controls (n = 20) will perform an emotional and the arithmetic task and receive visceral stimuli (by using a barostat) while placed in a functional magnetic resonance imaging scanner respectively during two different states, a) after oral administration of 10 mg Escitalopram, a well-known drug classified as Selective Serotonin Reuptake Inhibitor, packed in a coloured hydroxypropylmethylcellulose capsule, and b) during oral administration of a placebo, in a double-blinded randomized cross-over fashion. Background characteristics will be collected.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Irritable Bowel Syndrome

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
stimulated serotonergic activity
Arm Type
Experimental
Arm Title
unstimulated serotonergic activity
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
serotonergic stimulation
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
no serotonergic stimulation
Intervention Description
Oral administration of a placebo. The placebo will consist of a coloured hydroxypropylmethylcellulose capsule filled with microcrystalline cellulose.
Primary Outcome Measure Information:
Title
Differences in functional brain response pattern to the barostat in stimulated compared to unstimulated serotonergic activity
Description
functional magnetic resonance imaging
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Differences in functional brain response pattern to the Montreal Imaging Stress Task between stimulated and unstimulated serotonergic activity
Description
functional magnetic resonance imaging
Time Frame
1 week
Title
Differences in functional brain response pattern to the Emotional Attention Task between stimulated and unstimulated serotonergic activity
Description
functional magnetic resonance imaging
Time Frame
1 week
Title
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
Description
functional magnetic resonance imaging
Time Frame
1 week
Title
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
Description
functional magnetic resonance imaging
Time Frame
1 week
Title
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
Description
functional magnetic resonance imaging
Time Frame
1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria for the irritable bowel syndrome group: 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 Exclusion criteria for the irritable bowel syndrome group: 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 Grenade-splinter or metal-splinter in the body (e.g., eyes) Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant) Comprehensive tooth-implants or prothesis Operated in the head Operated in the heart Swallowed a video-capsule Non-corrected astigmatism Regular intake of antiinflammatory medication (including non-steroidal antiinflammatory drugs) Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning Any other reason the investigator feels the subject is not suitable for participation in the study Inclusion criteria for healthy group: Males and females aged 18-65 years of age Signed informed consent Exclusion criteria for the healthy group: Concurrent or recent history of gastrointestinal disorders or any somatic disorder 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) Concurrent psychiatric or psychological symptomatology defined as above cut-off on Montgomery Åsberg Depression Ratings Scale, above clinical cut-off on hospital anxiety and depression scale (equal to or above 8) 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 Grenade-splinter or metal-splinter in the body (e.g., eyes) Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant) Comprehensive tooth-implants or prothesis Operated in the head Operated in the heart Swallowed a video-capsule Non-corrected astigmatism Intake of anti-inflammatory medication (including non-steroidal antiinflammatory drugs) Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning Any other reason the investigator feels the subject is not suitable for participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Brummer, Prof.
Organizational Affiliation
Örebro University, Region Örebro County
Official's Role
Principal Investigator
Facility Information:
Facility Name
Örebro University, Region Örebro County
City
Örebro
ZIP/Postal Code
70182
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

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Effect of Serotonergic Stimulation on the Gut-brain Axis

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