免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Effect of Serotonergic Stimulation on the Gut-brain Axis

Effect of Serotonergic Stimulation on the Gut-brain Axis

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.

Condition or disease Intervention/treatment Phase
Healthy Irritable Bowel Syndrome Other: serotonergic stimulation Other: no serotonergic stimulation Not Applicable

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.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Serotonergic Stimulation on the Gut-brain Axis in Irritable Bowel Syndrome Patients Compared With Healthy Subjects
Actual Study Start Date : April 24, 2019
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : December 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: stimulated serotonergic activity Other: serotonergic stimulation
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.
Experimental: unstimulated serotonergic activity Other: no serotonergic stimulation
Oral administration of a placebo. The placebo will consist of a coloured hydroxypropylmethylcellulose capsule filled with microcrystalline cellulose.
Outcome Measures
Primary Outcome Measures :
  1. Differences in functional brain response pattern to the barostat in stimulated compared to unstimulated serotonergic activity [ Time Frame: 1 week ]
    functional magnetic resonance imaging


Secondary Outcome Measures :
  1. Differences in functional brain response pattern to the Montreal Imaging Stress Task between stimulated and unstimulated serotonergic activity [ Time Frame: 1 week ]
    functional magnetic resonance imaging

  2. Differences in functional brain response pattern to the Emotional Attention Task between stimulated and unstimulated serotonergic activity [ Time Frame: 1 week ]
    functional magnetic resonance imaging

  3. 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 [ Time Frame: 1 week ]
    functional magnetic resonance imaging

  4. 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 [ Time Frame: 1 week ]
    functional magnetic resonance imaging

  5. 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 [ Time Frame: 1 week ]
    functional magnetic resonance imaging


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Robert Brummer, Prof. 004619303731 robert.brummer@oru.se

Locations
Layout table for location information
Sweden
Örebro University, Region Örebro County Recruiting
Örebro, Sweden, 70182
Contact: Robert Brummer, Prof.    004619303731    robert.brummer@oru.se   
Sponsors and Collaborators
Örebro University, Sweden
Region Örebro County
Investigators
Layout table for investigator information
Principal Investigator: Robert Brummer, Prof. Örebro University, Region Örebro County
Tracking Information
First Submitted Date  ICMJE April 12, 2019
First Posted Date  ICMJE April 18, 2019
Last Update Posted Date February 24, 2021
Actual Study Start Date  ICMJE April 24, 2019
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2019) 		Differences in functional brain response pattern to the barostat in stimulated compared to unstimulated serotonergic activity [ Time Frame: 1 week ]
functional magnetic resonance imaging
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2019)
  • Differences in functional brain response pattern to the Montreal Imaging Stress Task between stimulated and unstimulated serotonergic activity [ Time Frame: 1 week ]
    functional magnetic resonance imaging
  • Differences in functional brain response pattern to the Emotional Attention Task between stimulated and unstimulated serotonergic activity [ Time Frame: 1 week ]
    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 [ Time Frame: 1 week ]
    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 [ Time Frame: 1 week ]
    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 [ Time Frame: 1 week ]
    functional magnetic resonance imaging
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Serotonergic Stimulation on the Gut-brain Axis
Official Title  ICMJE Effect of Serotonergic Stimulation on the Gut-brain Axis in Irritable Bowel Syndrome Patients Compared With Healthy Subjects
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE
  • Healthy
  • Irritable Bowel Syndrome
Intervention  ICMJE
  • Other: serotonergic stimulation
    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.
  • Other: no serotonergic stimulation
    Oral administration of a placebo. The placebo will consist of a coloured hydroxypropylmethylcellulose capsule filled with microcrystalline cellulose.
Study Arms  ICMJE
  • Experimental: stimulated serotonergic activity
    Intervention: Other: serotonergic stimulation
  • Experimental: unstimulated serotonergic activity
    Intervention: Other: no serotonergic stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 16, 2019) 		60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Robert Brummer, Prof. 004619303731 robert.brummer@oru.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03920410
Other Study ID Numbers  ICMJE 5HT
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Örebro University, Sweden
Study Sponsor  ICMJE Örebro University, Sweden
Collaborators  ICMJE Region Örebro County
Investigators  ICMJE
Principal Investigator: Robert Brummer, Prof. Örebro University, Region Örebro County
PRS Account Örebro University, Sweden
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯