Inflammation and Electroconvulsive Therapy

Does Electroconvulsive Therapy Cause Neuroinflammation? An [18F]FEPPA Positron Emission Tomography Study in Treatment Resistant Depression

The purpose of this study is to explore whether electroconvulsive therapy (ECT) accidentally leads to a side effect of brain inflammation. Patients with treatment resistant depression who are planning to take ECT will be subsequently approached to participate in the study.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder

Detailed Description

The first scan will take place before the first ECT session. The second scan will occur after a minimum of six ECT sessions (average 2.5 weeks). Secondary measures will include mood symptom severity, neurocognitive measures, peripheral inflammatory markers and TSPO genotype.

The hypothesis is that neuroinflammation will be increased by ECT.

There will be no alterations to standard care of depressed patients due to participation in the study.

• Study Type: Observational
• Enrollment (Actual): 5

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Community and tertiary care clinic

Description

Inclusion Criteria:

• stable physical health
• diagnosis of non-psychotic, non-catatonic, major depressive disorder, either unipolar or bipolar and a non-response to at least three clinical trials at appropriate dose of antidepressant medication from at least three different pharmacological classes
• at least a 17 on the17-item HDRS despite taking antidepressant treatment prior to ECT
• have not received ECT within the last 12 weeks

Exclusion Criteria:

• currently pregnant
• current substance abuse or dependence
• neurological or unstable medical illness
• use of anti-inflammatory drugs within the past month
• diazepam or other benzodiazepine use within the past month, except for lorazepam and clonazepam

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ECT and Treatment Resistant Depression; Subjects will be those with diagnosis of major depressive disorder that have not responded to many different treatments and who are planning to take electroconvulsive therapy (ECT). This group will receive two [18F]FEPPA PET scans, one baseline and one after an average of 2.5 weeks of ECT treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in translocator protein distribution volume (TSPO Vt) measured by [18F]FEPPA PET	Participants will have one [18F]FEPPA PET scan before they start ECT and a second PET scan on average after 2.5 weeks of ECT	Baseline scan and a second PET scan after an expected average time of 2.5 weeks of ECT treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
17-item Hamilton Depression Rating Scale (HDRS)	Scores on the 17-item HDRS will be taken at the time of the PET scan (baseline and post-ECT) to assess whether the magnitude of change in TSPO distribution volume is associated with changes in symptom severity.	Baseline and after average 2.5 weeks of ECT treatment
Neurocognitive Battery	Neurocognitive measures will be take at baseline and post-ECT to assess whether TSPO Vt is related to neurocognitive function. Neurocognitive battery includes: Autobiographical Memory Interview-Short Form (AMI-SF) Rey Auditory Verbal Learning Test (RAVLT) Wisconsin Card Sorting Test Comprehensive Trail Making Test Weschler Adult Intelligence Scale-Digit Symbol Subtest Stroop Color and Word Test Brief Visuospatial Memory Test Boston Naming Test Judgement of Line Orientation Weschler Test of Adult Reading	Baseline and after average 2.5 to 5 weeks of ECT treatment
Peripheral Inflammatory Markers	To explore whether peripheral and central inflammation are related markers of peripheral inflammation (TNF-alpha, IL-6, CRP and IL-1beta) will be measured and correlated to brain TSPO Vt.	Baseline and after average 2.5 to 5 weeks of ECT treatment

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Investigators: Principal Investigator: Jeffrey H Meyer, MD, PhD, Research Imaging Centre, Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: March 20, 2014
• First Submitted That Met QC Criteria: March 21, 2014
• First Posted (Estimate): March 26, 2014

Study Record Updates

• Last Update Posted (Actual): February 14, 2018
• Last Update Submitted That Met QC Criteria: February 13, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 074-2012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No