Brain Network Dynamics of Depression During Esketamine Treatment

NCT06012916 | Completed

• 1 other identifier: 22-0696
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a monocentric, observational clinical trial investigating the effect of Esketamine on brain network activity and a belief updating task in people with depression. We investigate the immediate and the long-term effect (approx. 8 weeks) of Esketamine on EEG signals, pupillometry and belief updating and the relation of those effects on depressive symptomatology.

Conditions

Depressive Disorder, Major

Keywords

Esketamine; Ketamine; Belief Updating; Pupillometry; EEG

Outcome Measures

Primary Outcomes (21)

• Change in Belief Updating in Session 1

  Participants rate the likelihood of a negative life event happening to them (E1) and their confidence in the estimate (C1). They are given a base rate (BR), described as the average lifetime probability of that event happening to someone with the same demographics. Participants will then again rate how likely the event could happen to them personally (E2). Outcome variables: update = \|E2 - E1\| and estimation error (ER) = \|E1 - BR\| News: "good news" (BR\< E1) or "bad news" (BR\>E1) trials. Within session relationships between update, C1, ER and covariates will be investigated using linear mixed models (LMMs) using an iterative model comparison process. The basic model will include fixed effect of News and a random intercept for individuals (id or ID). Potential covariates likely include ER, C1, the Revised Life Orientation Test (LOT-R), Ketamine Side Effect Tool (KSET), and scores of depression severity.

  10 minutes before Esketamine application compared to 2 hours after Esketamine application

• Change in Belief Updating in Session 2

  Participants rate the likelihood of a negative life event happening to them (E1) and their confidence in the estimate (C1). They are given a base rate (BR), described as the average lifetime probability of that event happening to someone with the same demographics. Participants will then again rate how likely the event could happen to them personally (E2). Outcome variables: update = \|E2 - E1\| and estimation error (ER) = \|E1 - BR\| News: "good news" (BR\< E1) or "bad news" (BR\>E1) trials. Within session relationships between update, C1, ER and covariates will be investigated using linear mixed models (LMMs) using an iterative model comparison process. The basic model will include fixed effect of News and a random intercept for ID (individuals). Potential covariates likely include ER, C1, the Revised Life Orientation Test (LOT-R), Ketamine Side Effect Tool (KSET), and scores of depression severity.

  10 minutes before Esketamine application compared to 2 hours after Esketamine application

• Change in Confidence in Beliefs Questionnaire in Session 1

  * Confidence in Beliefs Questionnaire investigates the strengths of belief in statements about the participant and about someone close to them. * Participants rate how certain they are about each belief, higher values imply higher certainty * Beliefs about oneself: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line * Beliefs about others: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line

  30 minutes before Esketamine application compared to 2 hours after Esketamine application

• Change in Confidence in Beliefs Questionnaire in Session 2

  * Confidence in Beliefs Questionnaire investigates the strengths of belief in statements about the participant and about someone close to them. * Participants rate how certain they are about each belief, higher values imply higher certainty * Beliefs about oneself: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line * Beliefs about others: 12 items (6 positive, 6 negative), Likert Scale 0 to 100, participants make a mark on a line

  30 minutes before Esketamine application compared to 2 hours after Esketamine application

• Change of Ketamine Side Effect Tool (KSET) in Session 1

  * Semi-structured interview to assess side effects of ketamine * Each item is scores from 0 (=never) to 3 (= severe) points * Sum scores and individual item scores can be analyzed.

  5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application

• Change of Ketamine Side Effect Tool (KSET) in Session 2

  * Semi-structured interview to assess side effects of ketamine * Each item is scores from 0 (=never) to 3 (= severe) points * Sum scores and individual item scores can be analyzed.

  5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application

• Change in Mood Likert Scale in Session 1

  * Likert Scales range from 0 to 100 * Participants make a mark on a line (left end = 0, right end = 100)

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change in Mood Likert Scale in Session 2

  * Likert Scales range from 0 to 100 * Participants make a mark on a line (left end = 0, right end = 100)

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short version (Q-LES-Q-SF)

  * Change in Q-LES-Q-SF between Session 1 and Session 2 * Q-LES-Q-SF is a brief, self-scoring quality of life rating scale. * Maximum percentage is 100%. Higher values imply higher quality of life

  Session 1 and session 2

• Change in Patient Health Questionnaire (PHQ-9)

  * Change in PHQ-9 between Session 1 and Session 2 * PHQ-9 is a brief, self-scoring depression rating scale. Higher values imply a higher depression severity. * Cut-off for depression is considered \>4 PHQ-9 points

  Session 1 and session 2

• Change in Hamilton Depression Rating Scale (HDRS)

  * Change in HDRS-17 between Session 1 and Session 2 * HDRS-17 is the most established depression rating scale. Higher values imply a higher depression severity. * Cut-off for depression is considered \>8 HDRS-17 points

  Session 1 and session 2

• Change of Resting State EEG - Power in Session 1

  * Changes in oscillatory power within an experimental session pre/post Esketamine application * Power will be analyzed in canonical frequency bands (e.g. alpha, beta, gamma, delta, theta)

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application

• Change of Resting State EEG - Power in Session 2

  * Changes in oscillatory power within an experimental session pre/post Esketamine application * Power will be analyzed in canonical frequency bands (e.g. alpha, beta, gamma, delta, theta)

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application

• Change of Resting State EEG - Connectivity in Session 1

  \- Changes in functional connectivity in canonical frequency band within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change of Resting State EEG - Connectivity in Session 2

  \- Changes in functional connectivity in canonical frequency band within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change of Resting State EEG - Source in Session 1

  \- Changes in spatial distribution and source of electric activity in canonical frequency band within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change of Resting State EEG - Source in Session 2

  \- Changes in spatial distribution and source of electric activity in canonical frequency band within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change of Resting State EEG - Aperiodic Signal in Session 1

  \- Changes in slope and offset of the aperiodic EEG signal within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change of Resting State EEG - Aperiodic Signal in Session 2

  \- Changes in slope and offset of the aperiodic EEG signal within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

• Change of Resting State EEG - Entropy in Session 1

  \- Changes of entropy measured in Lempel-Ziv Complexity and mutual information within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes in after Esketamine application

• Change of Resting State EEG - Entropy in Session 2

  \- Changes of entropy measured in Lempel-Ziv Complexity and mutual information within an experimental session pre/post Esketamine application

  5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application

Secondary Outcomes (6)

• Change in Task EEG - Event Related Potential (ERP) in Session 1

  30 minutes before Esketamine application and 100 minutes after Esketamine application

• Change in Task EEG - Event Related Potential (ERP) in Session 2

  30 minutes before Esketamine application and 100 minutes after Esketamine application

• Change in Task EEG - Time Frequency Analysis in Session 1

  30 minutes before Esketamine application and 100 minutes after Esketamine application

• Change in Task EEG - Time Frequency Analysis in Session 2

  30 minutes before Esketamine application and 100 minutes after Esketamine application

• Change in Pupillometry in Session 1

  30 minutes before Esketamine application and 100 minutes after Esketamine application

Study Arms (1)

Treatment Resistant Depression + Esketamine Treatment

This is a group of individuals with treatment resistant depression receiving Esketamine treatment as prescribed by their physician during outpatient appointments over several weeks at the Interventional Psychiatry outpatient clinic at University of North Carolina at Chapel Hill (UNC). After signing the informed consent, electroencephalogram (EEG) will be recorded before and after Esketamine administration by the attending physician. The participant will perform a cognitive task before and after the Esketamine administration as well as complete self-scored questionnaire regarding depressive symptoms, treatment expectation and Esketamine side-effects. Clinical information like the duration of episode, medication or clinician-rated depression scores will be retrieved from the charting system.

Drug: Esketamine nasal spray

Interventions

Esketamine nasal spray DRUG

This is an observational study. The Esketamine nasal spray is administered by the attending physician during a regular treatment appointment at the Interventional Psychiatry Clinic. Esketamine dosages may range between 28-84mg. The study does not interfere with the individual treatment plan in any way.

Also known as: Spravato

Treatment Resistant Depression + Esketamine Treatment

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The goal is to recruit individuals with an MDD diagnosis who are receiving Esketamine treatment.

You may qualify if:

• Major Depressive Disorder
• Receiving Esketamine nasal spray treatment for depression
• Ability to understand study procedures and sign an informed consent.

You may not qualify if:

• None

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

Carolina Center for Neurostimulation

Chapel Hill, North Carolina, 27516, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Flavio Frohlich, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2023
• First Posted: August 28, 2023
• Study Start: July 3, 2023
• Primary Completion: August 30, 2024
• Study Completion: August 30, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)