Clinical trial NCT03487926: Microglial Activation in Inflammatory Bowel Disease
Official title: Naturalistic Monitoring of Microglial Activation in Inflammatory Bowel Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Major Depressive Episode
Inflammatory Bowel Diseases
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: McMaster University
First posted: 2018-04-04
Enrollment: 40
Sex: ALL
Minimum age (years): 19
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Community and tertiary care clinic

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.

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

Primary outcomes:
measure: TSPO VT in prefrontal cortex, anterior cingulate cortex, and insula
timeFrame: within 3 to 4 weeks after initiation of screening
measure: change in TSPO VT in prefrontal cortex, anterior cingulate cortex, and insula before and after 3 to 6 months
timeFrame: 3 to 6 months
measure: MAO-B VT in prefrontal cortex, anterior cingulate cortex, insula in IBD compared to controls
timeFrame: within 3 to 4 weeks after initiation of screening
Secondary outcomes:
measure: TSPO VT in prefrontal cortex, anterior cingulate cortex, insula compared between Crohns disease and ulcerative colitis
timeFrame: within 3 to 4 weeks of initiating screening of subjects
measure: TSPO VT in prefrontal cortex, anterior cingulate cortex, insula compared between IBD with MDE compared to MDE controls
timeFrame: within 3 to 4 weeks after initiation of screening
measure: 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
timeFrame: 3 to 6 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health
state: Ontario
Study officials:
affiliation: Research Imaging Centre, Centre for Addiction and Mental Health
name: Jeffrey H Meyer, M.D.,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.