Microglial Activation in Inflammatory Bowel Disease

NCT ID: NCT03487926

Last Updated: 2025-04-22

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 40 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-09-14
• Study Completion Date: 2024-11-19

Brief Summary

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

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.

Conditions

Major Depressive Episode; Inflammatory Bowel Diseases

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Group 1 (IBD primary diagnosis)

Participants have active IBD

[18F]FEPPA

Intervention Type: RADIATION

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

Group 2( IBD + comorbid MDE)

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

[18F]FEPPA

Intervention Type: RADIATION

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

Group 3-Controls

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).

[18F]FEPPA

Intervention Type: RADIATION

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

Interventions

[18F]FEPPA

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

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

McMaster University

OTHER

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Jeff Meyer

Program Head, Neurochemical Imaging for Mood Disorders

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey H Meyer, M.D.,PhD

Role: PRINCIPAL_INVESTIGATOR

Research Imaging Centre, Centre for Addiction and Mental Health

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Countries

Canada

References

Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G, Suridjan I, Kennedy JL, Rekkas PV, Houle S, Meyer JH. Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry. 2015 Mar;72(3):268-75. doi: 10.1001/jamapsychiatry.2014.2427.

Reference Type: BACKGROUND

PMID: 25629589 (View on PubMed)

Attwells S, Setiawan E, Wilson AA, Rusjan PM, Mizrahi R, Miler L, Xu C, Richter MA, Kahn A, Kish SJ, Houle S, Ravindran L, Meyer JH. Inflammation in the Neurocircuitry of Obsessive-Compulsive Disorder. JAMA Psychiatry. 2017 Aug 1;74(8):833-840. doi: 10.1001/jamapsychiatry.2017.1567.

Reference Type: BACKGROUND

PMID: 28636705 (View on PubMed)

Holmes SE, Hinz R, Conen S, Gregory CJ, Matthews JC, Anton-Rodriguez JM, Gerhard A, Talbot PS. Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study. Biol Psychiatry. 2018 Jan 1;83(1):61-69. doi: 10.1016/j.biopsych.2017.08.005. Epub 2017 Aug 12.

Reference Type: BACKGROUND

PMID: 28939116 (View on PubMed)

Li H, Sagar AP, Keri S. Translocator protein (18kDa TSPO) binding, a marker of microglia, is reduced in major depression during cognitive-behavioral therapy. Prog Neuropsychopharmacol Biol Psychiatry. 2018 Apr 20;83:1-7. doi: 10.1016/j.pnpbp.2017.12.011. Epub 2017 Dec 19.

Reference Type: BACKGROUND

PMID: 29269262 (View on PubMed)

Other Identifiers

102-2016

Identifier Type: -

Identifier Source: org_study_id