Microglial Activation in Inflammatory Bowel Disease

Centre for Addiction and Mental Health40 enrolled

Overview

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: 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 : 1. 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. 2. The neuroinflammation (TSPO VT) in PFC, ACC, and insula regions will be reduced after treatment for IBD. The Secondary Hypothesis: 1. Elevations in neuroinflammation (TSPO VT) will be similar in those with ulcerative colitis and Crohn's disease. 2. Neuroinflammation (TSPO VT) will be greater in IBD with depression than in depression without IBD. 3. Biologics (TNFalpha antibody treatments), and fecal transplantation will be associated with greater reduction in neuroinflammation in brain than Sulfasalazine/5-Aminosalicylates. 4. 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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Major Depressive Episode Inflammatory Bowel Diseases

Interventions

[18F]FEPPARADIATION

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

Eligibility

Sex: ALLMin age: 19 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

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)

Time frame: 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)

Time frame: 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

Time frame: within 3 to 4 weeks after initiation of screening

Secondary Outcomes

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

Time frame: 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

Time frame: 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

Data from ClinicalTrials.gov

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