Microglial Activation in Inflammatory Bowel Disease

Study Overview
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Brief Summary
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The purpose of this study is to monitor microglial activation in participants with inflammatory bowel disease (IBD) and investigate the relationship that exists between these patients and their risk of acquiring major depressive episodes (MDE). Patients with both IBD and MDE will be subsequently approached to participate in the study.

Detailed Description
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Detailed Description: Participants may undergo up to 3 PET Scans : [18F]FEPPA PET (for TSPO) before and 3 to 6 months later and [11C]SL25.1188 PET (for MAO-B) as well as 1 MRI scan. The primary hypothesis is that : The neuroinflammation (TSPO VT) will be increased in PFC, ACC, and insula regions in those with inflammatory bowel disease (IBD) patients compared to healthy people. The neuroinflammation (TSPO VT) in PFC, ACC, and insula regions will be reduced after treatment for IBD. The Secondary Hypothesis: Elevations in neuroinflammation (TSPO VT) will be similar in those with ulcerative colitis and Crohn's disease. Neuroinflammation (TSPO VT) will be greater in IBD with depression than in depression without IBD. Biologics (TNFalpha antibody treatments), and fecal transplantation will be associated with greater reduction in neuroinflammation in brain than Sulfasalazine/5-Aminosalicylates. MAO-B VT will be elevated in in the PFC, ACC, and insula in IBD compared to healthy controls. There will be no alterations to standard care of patients due to participation in the study.

Official Title
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Naturalistic Monitoring of Microglial Activation in Inflammatory Bowel Disease

Conditions
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Major Depressive Episode, Inflammatory Bowel Diseases

Intervention / Treatment
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* Radiation: [18F]FEPPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 65 aside from IBD groups and common comorbidities of IBD, otherwise good physical health with no current active medical conditions. a lifetime diagnosis of IBD verified by medical record, which can include prescription for IBD treatment Exclusion Criteria: no history of neurological illness, excluding migraine no use of glucocorticoid antagonists or lithium or medications that bind with affinity higher than 500nM to peripheral benzodiazepine receptors (or TSPO) in the previous two months no use of herbal remedies in the previous month that would be expected to influence neuroinflammation non-cigarette smoking no history of abuse of substances that affect mood and negative urine drug screens for substances of abuse including cotinine (urine drug screen is done at screening and on each PET scan day) no history of psychotic symptoms not pregnant based on a negative pregnancy test (for women) not breastfeeding (for women) no recent treatment with electroconvulsive therapy or magnetic seizure therapy in the previous 6 months no coagulation disorders, or anticoagulant medication use no presence of metal objects or implanted electrical devices in the body that would preclude MRI scanning no claustrophobia no self-reported history of fainting from blood withdrawals size and weight does not exceed capacity of scanner, for which size may vary and weight is 350 lbs no history of undergoing a number of PET scans that, including the number of PET scans under this protocol, will bring the total to more than 8 PET scans/lifetime, exceeding permissible limit for subjects participating in research set by our centre's guidelines

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1 (IBD primary diagnosis)<br>Participants have active IBD | Radiation: [18F]FEPPA<br>* up to 3 PET Scans ([18F]FEPPA PET scans done 3 to 6 months apart, and one [11C]SL2511.88 PET scan) and 1 MRI<br>|
| Group 2( IBD + comorbid MDE)<br>1 [18F]FEPPA PET scan in those with IBD symptoms in the past 2 years as well present with MDE | Radiation: [18F]FEPPA<br>* up to 3 PET Scans ([18F]FEPPA PET scans done 3 to 6 months apart, and one [11C]SL2511.88 PET scan) and 1 MRI<br>|
| Group 3-Controls<br>Matched for Level of Depressive Symptoms and Otherwise Healthy -Subjects in an otherwise healthy state with major depressive episodes, obsessive compulsive disorder, or generalized anxiety disorder will provide psychiatric diagnosis matched controls to those with IBD. Data for group three will be largely obtained from previous recent studies (it is anticipated that 95% of this data is already available). | Radiation: [18F]FEPPA<br>* up to 3 PET Scans ([18F]FEPPA PET scans done 3 to 6 months apart, and one [11C]SL2511.88 PET scan) and 1 MRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TSPO VT in prefrontal cortex, anterior cingulate cortex, and insula | Between group comparison for 3 regions in IBD compared to controls (analysis done concurrently for group effect across 3 regions) | within 3 to 4 weeks after initiation of screening | 
| change in TSPO VT in prefrontal cortex, anterior cingulate cortex, and insula before and after 3 to 6 months | Change in TSPO VT for three regions (same units for each region) | 3 to 6 months | 
| MAO-B VT in prefrontal cortex, anterior cingulate cortex, insula in IBD compared to controls | Between group comparison for 3 regions in IBD compared to controls | within 3 to 4 weeks after initiation of screening | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TSPO VT in prefrontal cortex, anterior cingulate cortex, insula compared between Crohns disease and ulcerative colitis | comparison of TSPO VT in 3 regions between two types of inflammatory bowel disease | within 3 to 4 weeks of initiating screening of subjects | 
| TSPO VT in prefrontal cortex, anterior cingulate cortex, insula compared between IBD with MDE compared to MDE controls | Between group comparison for 3 regions in IBD compared to controls | within 3 to 4 weeks after initiation of screening | 
| change in TSPO VT in prefrontal cortex, anterior cingulate cortex, insula compared between naturalistic treatment with sulfasalazine/5-aminosalicylates versus other interventions like biologics or fecal transplantation | differential change in TSPO VT across 3 regions before and after 6 months in those receiving naturalistic treatment with sulfasalazine/5-aminosalicylates versus other naturalistic treatments of fecal transplantation or biologics | 3 to 6 months |