Microglial Activation in Inflammatory Bowel Disease

NCT03487926 | Completed DMC

• 1 other identifier: 102-2016
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Episode; Inflammatory Bowel Diseases

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• TSPO VT in prefrontal cortex, anterior cingulate cortex, insula compared between Crohns disease and ulcerative colitis

  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

  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

  3 to 6 months

Study Arms (3)

Group 1 (IBD primary diagnosis)

Participants have active IBD

Radiation: [18F]FEPPA

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

Radiation: [18F]FEPPA

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).

Radiation: [18F]FEPPA

Interventions

[18F]FEPPA 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 1 (IBD primary diagnosis); Group 2( IBD + comorbid MDE); Group 3-Controls

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Community and tertiary care clinic

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• McMaster University: collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M5T 1R8, Canada

Location

Related Publications (4)

• 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.

  PMID: 25629589 BACKGROUND

• 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.

  PMID: 28636705 BACKGROUND

• 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.

  PMID: 28939116 BACKGROUND

• 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.

  PMID: 29269262 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma and serum samples will be kept for analysis of genotype, peripheral inflammatory markers and protein binding.

MeSH Terms

Conditions

Inflammatory Bowel Diseases

Interventions

N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• Jeffrey H Meyer, M.D.,PhD

  Research Imaging Centre, Centre for Addiction and Mental Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Program Head, Neurochemical Imaging for Mood Disorders

Study Record Dates

• First Submitted: January 18, 2018
• First Posted: April 4, 2018
• Study Start: September 14, 2022
• Primary Completion: November 19, 2024
• Study Completion: November 19, 2024
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)