Molecular Imaging of Brain Inflammation in Depressive Disorders (DiME)

In a number of neuropsychiatric disorders such as depression, both brain inflammation and glutamate mediated excitotoxicity (cell death through over-activated stimulation) are suspected to play a key role. It is difficult, if not impossible, to determine the potential destructiveness of the inflammatory response seen in disease states by studying the brain's inflammatory cells (microglia) activity in isolation. The investigators are proposing to develop the means to concurrently study inflammatory response (i.e., microglial activity) and its potentially devastating consequence (i.e., glutamate excitotoxicity) across the entire brain in order to establish the importance of inflammation. In this study the investigators propose a phased clinical study whereby the early-phase involves the development of our capacity to study inflammation-mediated damage to brain cells, followed by a feasibility study in patients with clinical depression that tests whether concurrent inflammation and glutamate excess could be measured in key brain regions associated with a depressed mood state.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Major; Positron-Emission Tomography

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • St Joseph's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 105 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Able to pass MRI screening form (reviewed by a MRI technician)
• diagnosed with depression or healthy control participants with no present mental health disorder
• Good general health with no diseases expected to interfere with the study
• Subject is not pregnant, lactating, or of childbearing potential (must be practising effective form of birth control)
• Patient and healthy controls must not have an infection or an autoimmune disorder or persistent inflammation.

Description

Inclusion Criteria:

• screening form for MRI/PET is satisfactory after being reviewed by a radiologist
• diagnosed with depression or healthy control participants with no present mental health disorder
• Good general health with no diseases expected to interfere with the study
• Subject is not pregnant, lactating, or of childbearing potential (must be practicing effective form of birth control)
• Patient and healthy controls must not have an infection or an autoimmune disorder or persistent inflammation.

Exclusion Criteria:

• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
• use of Investigational agents within last month

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
PET/MRI using 18[F]EPPA ligand; given experimental ligand FEPPA during MRI/PET scan to identify glutamate activity in the brain using FEPPA ligand

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammation-related excitotoxicity in the brain	Cross sectional MRI/PET scan will be used to identify inflammation related excitotoxicity in the brain in healthy individuals and those diagnosed with major depression.	single time. Data collected at baseline with no follow up.

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Investigators: Principal Investigator: Lena Palaniyappan, MBBS/PhD, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2017
• Primary Completion (Actual): March 20, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: November 29, 2016
• First Submitted That Met QC Criteria: December 2, 2016
• First Posted (Estimate): December 6, 2016

Study Record Updates

• Last Update Posted (Actual): April 9, 2020
• Last Update Submitted That Met QC Criteria: April 7, 2020
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Mood Disorders; Central Nervous System Infections; Depression; Depressive Disorder; Encephalitis; Inflammation; Depressive Disorder, Major; Infectious Encephalitis
• Other Study ID Numbers: 100128

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO