Intravenous Ketamine Plus Neurocognitive Training for Depression

NCT03237286 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: STUDY190404141R01MH113857
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 1

Brief Summary

This study has two aims: 1) to characterize the effects of intravenous ketamine on neurocognitive markers in depressed patients; 2) to test the efficacy of a synergistic intervention for depression combining intravenous ketamine with neurocognitive training. Three of the primary outcomes listed (fMRI functional connectivity; Implicit Association Test; cognitive flexibility testing) pertain to Aim 1. For Aim 2, one primary clinical outcome (MADRS, a clinician-administered measure of depression severity) pertains to the acute (30-day) phase, while the QIDS (a self-report measure of depression severity) becomes the primary clinical outcome during the 12-month naturalistic follow-up.

Conditions

Depression

Keywords

depression; ketamine; neurocognitive; fMRI; cognitive training

Outcome Measures

Primary Outcomes (5)

• Montgomery Asberg Depression Scale

  Clinician-rated depression (range: 0-60; higher scores = worse outcome)

  Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported

• Executive-salience Network Functional Connectivity

  fMRI measure (beta weights where larger beta weight = stronger connectivity)

  Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported

• Implicit Self-representations

  Implicit Association Test composite difference score (performance-based measure; range = -inf-inf; high score=worse outcome; negatively signed value indicates associating oneself more strongly with positive than negative attributes)

  Trajectories from 24 hours through Day 30 post-infusion, Day 5 reported

• Cognitive Flexibility

  Neurocognitive testing via NIH Toolbox DCCS fully-corrected T-scores (range = 0-100; high score=better outcome)

  Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported

• Quick Inventory of Depressive Symptoms

  Self-reported depression (range: 0-27; higher scores = worse outcome)

  Trajectories from Day 30 through 12 months post-infusion (naturalistic follow-up), Month 12 reported

Secondary Outcomes (15)

• Executive-salience Network Functional Connectivity During Resting State

  Trajectories from 24 hours through Day 30 post-infusion, 24 hours reported

• Affective Flexibility

  Trajectories from 24 hours through Day 30 post-infusion, Day 30 reported

• PROMIS Measures-depression

  Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

• PROMIS Measures-anxiety

  Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

• PROMIS Measures-anger

  Trajectories from 24 hours through Month 12 post-infusion, Month 12 reported

Study Arms (3)

Ketamine + Cognitive Training

EXPERIMENTAL

Drug: Intravenous ketamine; Behavioral: Computer-based Cognitive Training

Ketamine + Sham Training

SHAM COMPARATOR

Drug: Intravenous ketamine

Saline + Cognitive Training

PLACEBO COMPARATOR

Behavioral: Computer-based Cognitive Training

Interventions

Intravenous ketamine DRUG

Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.

Ketamine + Cognitive Training; Ketamine + Sham Training

Computer-based Cognitive Training BEHAVIORAL

Computer-based Cognitive Training will be delivered following intravenous ketamine to test whether learning during a post-ketamine "window of opportunity" might extend relief from depression.

Ketamine + Cognitive Training; Saline + Cognitive Training

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants will:
• be between the ages of 18 and 60 years,
• have not responded to one or more adequate trials of FDA-approved antidepressants within the current depressive episode, determined by Antidepressant Treatment History Form
• score ≥ 25 on the Montgomery Asberg Depression Rating Scale (MADRS)
• score \>1SD above the normative mean on the Cognitive Triad Inventory "self" subscale \*OR\* \<1SD below the normative mean on the Rosenberg self-esteem scale
• possess a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document
• agree to sign a release of information (ROI), identifying another individual \[friend, family member, etc.\] as a contact person while the patient is enrolled in the study.

You may not qualify if:

• Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., substance use disorder); or lifetime recreational ketamine or PCP use
• Use of a Monoamine Oxidase Inhibitor (MAOI) within the previous 2 weeks
• Current pregnancy or breastfeeding, or failure to engage in an effective birth control strategy throughout the duration of the study
• Acute suicidality or other psychiatric crises requiring treatment escalation.
• Changes made to treatment regimen within 4 weeks of baseline assessment
• Reading level \<6th grade
• 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 board-certified 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.
• Past intolerance or hypersensitivity to ketamine or midazolam.
• Patients taking medications with known activity at the NMDA or AMPA glutamate receptor \[e.g., riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine\], or the muopioid receptor.
• Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide
• Patients who have received ECT in the past 6 months prior to Screening.
• Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS).
• Patients taking benzodiazepines (within 8 hours of infusion) or GABA agonists

Sponsors & Collaborators

• Rebecca Price: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Western Psychiatric Institute and Clinic

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• Hossein S, Woody ML, Panny B, Spotts C, Wallace ML, Mathew SJ, Howland RH, Price RB. Functional connectivity subtypes during a positive mood induction: Predicting clinical response in a randomized controlled trial of ketamine for treatment-resistant depression. J Psychopathol Clin Sci. 2025 Apr;134(3):228-238. doi: 10.1037/abn0000951. Epub 2024 Sep 23.

  PMID: 39311825 DERIVED

• Price RB, Wallace ML, Mathew SJ, Howland RH. One-Year Outcomes Following Intravenous Ketamine Plus Digital Training Among Patients with Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 May 1;6(5):e2312434. doi: 10.1001/jamanetworkopen.2023.12434.

  PMID: 37155171 DERIVED

• Price RB, Panny B, Degutis M, Griffo A. Repeated measurement of implicit self-associations in clinical depression: Psychometric, neural, and computational properties. J Abnorm Psychol. 2021 Feb;130(2):152-165. doi: 10.1037/abn0000651. Epub 2020 Dec 3.

  PMID: 33271040 DERIVED

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Dr. Rebecca Price
• Organization: University of Pittsburgh

pricerb@upmc.edu

412-383-2150

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 2, 2017
• Study Start: December 1, 2017
• Primary Completion: October 18, 2022
• Study Completion: October 18, 2022
• Last Updated: March 19, 2024
• Results First Posted: November 1, 2023

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: We will comply with all NIMH guidelines regarding data repository/sharing.

Locations

US (1)