Repeated Neurocognitive Measurements in Depressed Patients

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.

Study Overview

• Status: Completed
• Conditions: Depression, Unipolar
• Intervention / Treatment: Drug: Intravenous Ketamine

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Western Psychiatric Institute And Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All participants will:

1. be between the ages of 18 and 60 years,
2. score ≥ 14 on the Hamilton Depression Rating Scale (Ham-D)
3. 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:

1. Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., ongoing moderate-to-severe substance use disorder);
2. 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.
3. 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.
4. Changes made to treatment regimen within 4 weeks of baseline assessment.
5. Reading level <6th grade as per patient self-report.
6. Patients who have received ECT in the past 2 months prior to Screening.

Ketamine phase subsample additional exclusion criteria:

1. Patients currently taking any psychotropic medication.
2. Lifetime recreational ketamine or PCP use
3. Current pregnancy or breastfeeding
4. 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.
5. Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for drugs of abuse], physical examination, or ECG.
6. 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.
7. Patients with one or more seizures without a clear and resolved etiology.
8. Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening.
9. Past intolerance or hypersensitivity to ketamine.
10. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor [e.g., riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, Dcycloserine], or the mu-opioid receptor.
11. Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI Intrinsic Connectivity: Default Mode Network	functional connectivity normalized correlation values within default mode network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)	24hrs post-intervention
fMRI Intrinsic Connectivity: Frontoparietal Control Network	functional connectivity normalized correlation values within frontoparietal control network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)	24hrs post-intervention
fMRI Intrinsic Connectivity: Limbic Network	functional connectivity normalized correlation values within limbic network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)	24hrs post-intervention
fMRI Intrinsic Connectivity: Salience Network	functional connectivity normalized correlation values within salience ventral attentional network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)	24hrs post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	24hrs post-intervention
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	5 days post-intervention
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	12 days post-intervention
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	24hrs post-intervention
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	5 days post-intervention
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	12 days post-intervention
fMRI Intrinsic Connectivity: Dorsal Attention Network	functional connectivity normalized correlation values within dorsal attention network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)	24hrs post-intervention
fMRI Intrinsic Connectivity: Somatosensory Motor Network	functional connectivity normalized correlation values within somatosensory motor network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)	24hrs post-intervention
fMRI Intrinsic Connectivity: Visual Network	functional connectivity normalized correlation values within visual network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)	24hrs post-intervention
Hamilton Depression Rating Scale (Modified Score)	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	24hrs post-intervention
Hamilton Depression Rating Scale (Modified Score)	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	5 days post-intervention
Hamilton Depression Rating Scale (Modified Score)	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	12 days post-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Rating Via Quantitative Sensory Testing	Pain rating obtained from Quantitative Sensory Testing by mechanical temporal summation (range: 0-10; higher score=more pain)	1-hour post-infusion
PROMIS Pain Intensity Score	PROMIS Pain Intensity Short Form scale T-score (range=0-100; higher score=worse pain)	1-hour post-infusion
PROMIS Pain Interference Score	PROMIS Pain Interference Short Form scale T-score (range=0-100; higher score=worse pain)	1-hour post-infusion
Dual Probe Video Task	attentional bias (proportion score) towards sad film clips (range: 0 to +1.0; higher score=greater attention bias towards sad films)	infusion +24 hours (1 day)

Collaborators and Investigators

• Sponsor: Rebecca Price

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2021
• Primary Completion (Actual): July 15, 2023
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; 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: STUDY21040075

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