Clinical trial NCT06012916: Brain Network Dynamics of Depression During Esketamine Treatment
Official title: Brain Network Dynamics of Depression During Esketamine Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Depressive Disorder, Major
Keywords: Esketamine
Ketamine
Belief Updating
Pupillometry
EEG
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
First posted: 2023-08-28
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The goal is to recruit individuals with an MDD diagnosis who are receiving Esketamine treatment.

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.

Detailed description: The FDA approved the S-enantiomer of Ketamine in a nasal spray formulation (Esketamine, Spravato) in 2019 for treatment resistant depression in conjunction with an oral antidepressant. Albeit showing impressive short term clinical effects, the neurophysiological mechanism leading to clinical improvements are not understood. The investigators aim to add missing knowledge about the network dynamics of Esketamine in depression. Besides changes of neural signatures, Esketamine might impact cognitive processes like belief updating.

Previous studies have shown that people update their expectations of future life events after receiving novel information. The Belief Updating Task (BUT) measures this belief update in reaction to new information. Healthy individuals have been shown to update their beliefs "optimistically", making larger changes in their expectations in response to good news. Individuals with depression lack this optimistic belief update bias. Therefore, the investigators also aim to examine if Esketamine treatment reinstates the optimistic bias, how those changes are mediated by neurophysiological changes during the task and if a change in belief updated is related to a change of depressive symptoms.

The first session takes place at the start of the Esketamine treatment period, whereas the second experimental session is conducted closer to the end of the treatment period. In both experimental sessions, EEG/pupillometry and cognitive measurements are taken before and after Esketamine administration. Analyses will assess pre/post Esketamine effects within a session and between two sessions.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* None

Primary outcomes:
measure: Change in Belief Updating in Session 1
timeFrame: 10 minutes before Esketamine application compared to 2 hours after Esketamine application
measure: Change in Belief Updating in Session 2
timeFrame: 10 minutes before Esketamine application compared to 2 hours after Esketamine application
measure: Change in Confidence in Beliefs Questionnaire in Session 1
timeFrame: 30 minutes before Esketamine application compared to 2 hours after Esketamine application
measure: Change in Confidence in Beliefs Questionnaire in Session 2
timeFrame: 30 minutes before Esketamine application compared to 2 hours after Esketamine application
measure: Change of Ketamine Side Effect Tool (KSET) in Session 1
timeFrame: 5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application
measure: Change of Ketamine Side Effect Tool (KSET) in Session 2
timeFrame: 5 minutes before Esketamine application, and 50, 95, and 130 minutes after Esketamine application
measure: Change in Mood Likert Scale in Session 1
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change in Mood Likert Scale in Session 2
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change in Quality of Life Enjoyment and Satisfaction Questionnaire, short version (Q-LES-Q-SF)
timeFrame: Session 1 and session 2
measure: Change in Patient Health Questionnaire (PHQ-9)
timeFrame: Session 1 and session 2
measure: Change in Hamilton Depression Rating Scale (HDRS)
timeFrame: Session 1 and session 2
measure: Change of Resting State EEG - Power in Session 1
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application
measure: Change of Resting State EEG - Power in Session 2
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and130 minutes after Esketamine application
measure: Change of Resting State EEG - Connectivity in Session 1
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change of Resting State EEG - Connectivity in Session 2
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change of Resting State EEG - Source in Session 1
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change of Resting State EEG - Source in Session 2
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change of Resting State EEG - Aperiodic Signal in Session 1
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change of Resting State EEG - Aperiodic Signal in Session 2
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
measure: Change of Resting State EEG - Entropy in Session 1
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes in after Esketamine application
measure: Change of Resting State EEG - Entropy in Session 2
timeFrame: 5 minutes before Esketamine application, and 15, 35, 50, 75, 95, and 130 minutes after Esketamine application
Secondary outcomes:
measure: Change in Task EEG - Event Related Potential (ERP) in Session 1
timeFrame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
measure: Change in Task EEG - Event Related Potential (ERP) in Session 2
timeFrame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
measure: Change in Task EEG - Time Frequency Analysis in Session 1
timeFrame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
measure: Change in Task EEG - Time Frequency Analysis in Session 2
timeFrame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
measure: Change in Pupillometry in Session 1
timeFrame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
measure: Change in Pupillometry in Session 2
timeFrame: 30 minutes before Esketamine application and 100 minutes after Esketamine application
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Carolina Center for Neurostimulation
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Flavio Frohlich, PhD
role: PRINCIPAL_INVESTIGATOR
References: