Repeated Neurocognitive Measurements in Depressed Patients

Sponsor

Jay Fournier (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05991232

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

In this project, we will A) track the functioning of a collection of potential neurobiological targets for depression over time, B) examine how fluctuations in the functioning of those targets relates to real-world functioning, and C) in a subset of the sample, determine how the functioning in those targets is altered by a single dose of ketamine.

Condition or Disease	Intervention/Treatment	Phase
Depression, Unipolar	Drug: Intravenous Ketamine	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Repeated Neurocognitive Measurements in Depressed Patients

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Nov 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravenous Ketamine Open-label ketamine infusion	Drug: Intravenous Ketamine Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min) Other Names: Ketalar

Arm

Intervention/Treatment

Experimental: Intravenous Ketamine

Open-label ketamine infusion

Drug: Intravenous Ketamine

Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min)

Other Names:

Ketalar

Outcome Measures

Primary Outcome Measures

fMRI resting state connectivity [24hrs post-intervention]
directed connectivity beta weights between default mode, frontoparietal, limbic/affective, and salience networks (larger beta weight = stronger connectivity)

Secondary Outcome Measures

Montgomery-Asberg Depression Rating Scale [24hrs post-intervention]
Clinician-rated depression (range: 0-60; higher scores = worse outcome)
Montgomery-Asberg Depression Rating Scale [5 days post-intervention]
Clinician-rated depression (range: 0-60; higher scores = worse outcome)
Montgomery-Asberg Depression Rating Scale [12 days post-intervention]
Clinician-rated depression (range: 0-60; higher scores = worse outcome)
Hamilton Depression Rating Scale [24hrs post-intervention]
Clinician-rated depression (range: 0-52; higher scores = worse outcome)
Hamilton Depression Rating Scale [5 days post-intervention]
Clinician-rated depression (range: 0-52; higher scores = worse outcome)
Hamilton Depression Rating Scale [12 days post-intervention]
Clinician-rated depression (range: 0-52; higher scores = worse outcome)
Quick Inventory of Depressive Symptoms [24hrs post-intervention]
Self-reported depression (range: 0-27; higher scores = worse outcome)
Quick Inventory of Depressive Symptoms [5 days post-intervention]
Self-reported depression (range: 0-27; higher scores = worse outcome)
Quick Inventory of Depressive Symptoms [12 days post-intervention]
Self-reported depression (range: 0-27; higher scores = worse outcome)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All participants will:

be between the ages of 18 and 60 years,
score ≥ 14 on the Hamilton Depression Rating Scale (Ham-D)
possess a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document

Exclusion Criteria:

All participants:

Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., ongoing moderate-to-severe substance use disorder);
Failure to meet standard MRI inclusion criteria: those who have cardiac pacemakers, neural pacemakers, cochlear implants, metal braces, or other non-MRI-compatible metal objects in their body. History of significant injury or surgery to the brain or spinal cord that would impair interpretation of results.
Acute suicidality or other psychiatric crises requiring treatment escalation. We will use the Columbia Suicide Severity Rating Scale (CSSRS) as both an initial exclusion criteria (CSSRS "Baseline/Screening" Version for past 1month period) and as grounds for rescue/removal (CSSRS "Since Last Visit" form). The CSSRS will be administered using a paper form by an experienced and thoroughly trained clinical assessor on the study team. Subjects with CSSRS suicide ideation scores scored "yes" on items 4 (active suicidal ideation with some intent to act) and/or 5 (active suicidal ideation with specific plan and intent) will be excluded from the study, and if enrolled, will be exited from the study and referred immediately to the nearest emergency mental health facility for additional thorough assessment and appropriate treatment referral.
Changes made to treatment regimen within 4 weeks of baseline assessment.
Reading level <6th grade as per patient self-report.
Patients who have received ECT in the past 2 months prior to Screening.

Ketamine phase subsample additional exclusion criteria:

Patients currently taking any psychotropic medication.
Lifetime recreational ketamine or PCP use
Current pregnancy or breastfeeding
For ketamine phase entry, patients must be reasonable medical candidates for ketamine infusion, as determined by a physician co-investigator. Serious, unstable medical illnesses including respiratory [obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics], cardiovascular [including ischemic heart disease and uncontrolled hypertension], and neurologic [including history of severe head injury] will be exclusions.
Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for drugs of abuse], physical examination, or ECG.
Uncontrolled or poorly controlled hypertension, as determined by a physician co-investigator's review of vitals collected during screening and any other relevant medical history/records.
Patients with one or more seizures without a clear and resolved etiology.
Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening.
Past intolerance or hypersensitivity to ketamine.
Patients taking medications with known activity at the NMDA or AMPA glutamate receptor [e.g., riluzole, amantadine, memantine, topiramate, dextromethorphan, Dcycloserine], or the mu-opioid receptor.
Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide.