Microglial Activation in Inflammatory Bowel Disease

Center for Addiction and Mental Health (CAMH)

Status: Completed

Conditions: Major Depressive Episode; Inflammatory Bowel Diseases

Treatments: Radiation: [18F]FEPPA

Study type: Observational

Funder types: Other

Identifiers

NCT03487926

102-2016

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 40 patients

Sex: All

Ages: 19 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

40 participants in 3 patient groups

Group 1 (IBD primary diagnosis)

Description:

Participants have active IBD

Treatment:

Radiation: [18F]FEPPA

Group 2( IBD + comorbid MDE)

Description:

1 \[18F\]FEPPA PET scan in those with IBD symptoms in the past 2 years as well present with MDE

Treatment:

Radiation: [18F]FEPPA

Group 3-Controls

Description:

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).

Treatment:

Radiation: [18F]FEPPA