Auditory MMN EEG in TRD in Response to Ketamine

Deciphering Metacognition and Treatment Response in Depression With a Novel Digital Paradigm

To develop and test a neurocomputational model of ketamine treatment response predictions in TRD.

Study Overview

• Status: Recruiting
• Conditions: Treatment-resistant Depression (TRD)
• Intervention / Treatment: Drug: Ketamine

Detailed Description

The investigators propose applying a previously validated computational model of the MMN and the ensuing effects of NMDAR antagonism to predict treatment response following ketamine infusions in TRD patients and distinguish ketamine's antisuicidal effects from those related to mood improvements. The study has two subgoals: first, the computational mechanisms underlying MMN reductions that predict ketamine treatment response in TRD patients will be examined. Second, the computational mechanisms will be linked to their underlying neural causes using neural circuit models. Beyond understanding ketamine's short- and long-term mechanisms of action in TRD, the parameters obtained from fitting these models to noninvasive EEG recordings may facilitate single-patient treatment predictions. If successful, this approach may provide clinically useful prognostic statements in individual patients.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Venkat Bhat, MD MSc; Phone Number: 76404 416-360-4000; Email: Venkat.Bhat@unityhealth.to

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B1M8
      • Recruiting
      • St. Michael's Hospital
      • Principal Investigator: Venkat Bhat, MD MSc
      • Contact: Venkat Bhat, MD MSc; Phone Number: 76404 4163604000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patient participants diagnosed as suffering from a Treatment-Resistant Depression (TRD) that meet the criteria from Diagnosis and Statistical Manual for Mental Disorders (DSM-5), will be eligible to participate in this data collection study. Participants who have agreed to receive ketamine treatments as part of the Interventional Psychiatry Clinical Program at St. Michael's Hospital will be approached and recruited.

Description

Inclusion Criteria:

1.18 to 65 years of age 2. Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for MDD and in a Major Depressive Episode and ≥10 on the Montgomery-Asberg Depression Rating Scale (MADRS).

3. Competent to consent-based on their ability to provide a spontaneous narrative description of the key elements of the study.

4. Failure of at least two trials of antidepressant therapy during the current episode (treatment-resistant depression) and receiving ketamine treatment clinically as administered by their clinician 5. Staying on stable dosages of any concomitant psychotropic medications.

Exclusion Criteria:

1. History of bipolar disorder or psychosis
2. Current substance use or history of substance use during the past year (excluding nicotine and caffeine use disorder)
3. Concomitant major and unstable medical or neurologic illness or a history of seizures.
4. Non-English-speaking individuals.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	Remission, defined as MADRS <10, and suicide risk reduction is defined as a ≥ 50% reduction in the suicidal ideation item of the MADRS scale from baseline	4 weeks following the baseline visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modelling	Modelling the underlying cognitive and behavioural mechanisms to their neural causes from the effect of ketamine on TRD patients	2 weeks following the baseline visit

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Centre for Addiction and Mental Health; Toronto Metropolitan University

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: June 24, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depressive Disorder; Depression; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 22-084

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No