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Intravenous Ketamine Plus Neurocognitive Training for Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03237286
Recruitment Status : Active, not recruiting
First Posted : August 2, 2017
Last Update Posted : September 10, 2022
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Rebecca Price, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE July 28, 2017
First Posted Date  ICMJE August 2, 2017
Last Update Posted Date September 10, 2022
Actual Study Start Date  ICMJE December 1, 2017
Estimated Primary Completion Date November 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2019)
  • Montgomery Asberg Depression Scale [ Time Frame: 1 day to 2 weeks ]
    Clinician-rated depression
  • Executive-salience network functional connectivity [ Time Frame: 1 day to 2 weeks ]
    fMRI measure
  • Implicit self-representations [ Time Frame: 1 day to 2 weeks ]
    Implicit Association Test
  • Cognitive Flexibility [ Time Frame: 1 day to 2 weeks ]
    Neurocognitive testing
  • Quick Inventory of Depressive Symptoms [ Time Frame: 1 day to 2 weeks ]
    Self-reported depression
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2017)
  • Montgomery Asberg Depression Scale [ Time Frame: 1 day to 2 weeks ]
  • Executive-salience network functional connectivity [ Time Frame: 1 day to 2 weeks ]
    fMRI measure
  • Implicit self-representations [ Time Frame: 1 day to 2 weeks ]
    Implicit Association Test
  • Cognitive Flexibility [ Time Frame: 1 day to 2 weeks ]
    Neurocognitive testing
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2020)
  • Neural activation and connectivity patterns [ Time Frame: 1 day to 2 weeks ]
    fMRI measures
  • Affective flexibility/inhibition [ Time Frame: 1 day to 2 weeks ]
    Neurocognitive testing
  • PROMIS measures-depression [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported depression T-score range: 0-100 (higher score = worse outcome)
  • PROMIS measures-anxiety [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anxiety T-score range: 0-100 (higher score = worse outcome)
  • PROMIS measures-anger [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported anger T-score range: 0-100 (higher score = worse outcome)
  • PROMIS measures-positive affect [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported positive affect/well-being T-score range: 0-100 (higher score = better outcome)
  • PROMIS measures-sleep disturbance [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported sleep disturbance T-score range: 0-100 (higher score = worse outcome)
  • PROMIS measures-cognitive function [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported cognitive function T-score range: 0-100 (higher score = better outcome)
  • PROMIS measures-substance use [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported substance use T-score range: 0-100 (higher score = worse outcome)
  • PROMIS measures-alcohol [ Time Frame: 1 day to 2 weeks ]
    Patient-Reported Outcomes Measurement Information System (PROMIS) measure: Self-reported alcohol use T-score range: 0-100 (higher score = worse outcome)
  • Cognitive Triad Inventory [ Time Frame: 1 day to 2 weeks ]
    Negative perceptions of self, future, & world
  • Columbia-Suicide Severity Rating Scale [ Time Frame: 1 day to lifetime ]
    Suicidality and patient safety
  • WHO Disability Assessment Scale (SR) [ Time Frame: 1 to 30 days ]
    Global functioning
  • Cognitive Flexibility Scale [ Time Frame: 1 day to lifetime ]
    Self-reported cognitive flexibility
  • Neuroplasticity-related markers in blood [ Time Frame: 1 day to 2 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2017)
  • Quick Inventory of Depressive Symptoms [ Time Frame: 1 day to 2 weeks ]
    Self-reported depression
  • Neural activation and connectivity patterns [ Time Frame: 1 day to 2 weeks ]
    fMRI measures
  • Affective flexibility/inhibition [ Time Frame: 1 day to 2 weeks ]
    Neurocognitive testing
  • Mood and Anxiety Symptom Questionnaire [ Time Frame: 1 day to 2 weeks ]
    Self-reported depression, anxiety, and distress
  • Cognitive Triad Inventory [ Time Frame: 1 day to 2 weeks ]
    Negative perceptions of self, future, & world
  • Columbia-Suicide Severity Rating Scale [ Time Frame: 1 day to lifetime ]
    Suicidality and patient safety
  • WHO Disability Assessment Scale (SR) [ Time Frame: 1 to 30 days ]
    Global functioning
  • Cognitive Flexibility Scale [ Time Frame: 1 day to lifetime ]
    Self-reported cognitive flexibility
  • Neuroplasticity-related markers in blood [ Time Frame: 1 day to 2 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravenous Ketamine Plus Neurocognitive Training for Depression
Official Title  ICMJE Testing a Synergistic, Neuroplasticity-Based Intervention for Depressive Neurocognition
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Depression
Intervention  ICMJE
  • Drug: Intravenous ketamine
    Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.
  • Behavioral: Computer-based Cognitive Training
    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.
Study Arms  ICMJE
  • Experimental: Ketamine + Cognitive Training
    Interventions:
    • Drug: Intravenous ketamine
    • Behavioral: Computer-based Cognitive Training
  • Sham Comparator: Ketamine + Sham Training
    Intervention: Drug: Intravenous ketamine
  • Placebo Comparator: Saline + Cognitive Training
    Intervention: Behavioral: Computer-based Cognitive Training
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 30, 2021)
154
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2017)
150
Estimated Study Completion Date  ICMJE November 15, 2022
Estimated Primary Completion Date November 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Participants will:

  1. be between the ages of 18 and 60 years,
  2. have not responded to one or more adequate trials of FDA-approved antidepressants within the current depressive episode, determined by Antidepressant Treatment History Form
  3. score ≥ 25 on the Montgomery Asberg Depression Rating Scale (MADRS)
  4. 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
  5. possess a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document
  6. 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.

Exclusion Criteria:

  1. Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., substance use disorder); or lifetime recreational ketamine or PCP use
  2. Use of a Monoamine Oxidase Inhibitor (MAOI) within the previous 2 weeks
  3. 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, especially in the eye. Dental fillings do not present a problem. Plastic or removable dental appliances do not require exclusion. History of significant injury or surgery to the brain or spinal cord that would impair interpretation of results.
  4. Current pregnancy or breastfeeding, or failure to engage in an effective birth control strategy throughout the duration of the study
  5. Acute suicidality or other psychiatric crises requiring treatment escalation.
  6. Changes made to treatment regimen within 4 weeks of baseline assessment
  7. Reading level <6th grade
  8. For study entry, patients must be reasonable medical candidates for ketamine infusion, as determined by a board-certified physician co-investigator during study screening. 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.
  9. Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for drugs of abuse], physical examination, or ECG.
  10. 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.
  11. Patients with one or more seizures without a clear and resolved etiology.
  12. Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening. Birth control is not an exclusion.
  13. Past intolerance or hypersensitivity to ketamine or midazolam.
  14. 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.
  15. Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide
  16. Patients who have received ECT in the past 6 months prior to Screening.
  17. Patients currently receiving treatment with vagus nerve stimulation (VNS) or repetitive transcranial stimulation (rTMS).
  18. Patients taking benzodiazepines (within 8 hours of infusion) or GABA agonists
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03237286
Other Study ID Numbers  ICMJE STUDY19040414
1R01MH113857 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: We will comply with all NIMH guidelines regarding data repository/sharing.
Time Frame: We will comply with all NIMH guidelines regarding data repository/sharing.
Current Responsible Party Rebecca Price, University of Pittsburgh
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Rebecca Price
Original Study Sponsor  ICMJE University of Pittsburgh
Collaborators  ICMJE National Institute of Mental Health (NIMH)
Investigators  ICMJE Not Provided
PRS Account University of Pittsburgh
Verification Date September 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP