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Intravenous Ketamine Plus Neurocognitive Training for Depression

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ClinicalTrials.gov Identifier: NCT03237286
Recruitment Status : Recruiting
First Posted : August 2, 2017
Last Update Posted : July 30, 2018
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Rebecca Price, University of Pittsburgh

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.

Condition or disease Intervention/treatment Phase
Depression Drug: Intravenous ketamine Behavioral: Computer-based Cognitive Training Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Testing a Synergistic, Neuroplasticity-Based Intervention for Depressive Neurocognition
Actual Study Start Date : December 1, 2017
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Ketamine + Cognitive Training 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.

Sham Comparator: Ketamine + Sham Training Drug: Intravenous ketamine
Intravenous ketamine is given at a subanesthetic dose, which previous research suggests is safe and efficacious for rapid relief from depression.

Placebo Comparator: Saline + Cognitive Training 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.




Primary Outcome Measures :
  1. Montgomery Asberg Depression Scale [ Time Frame: 1 day to 2 weeks ]
  2. Executive-salience network functional connectivity [ Time Frame: 1 day to 2 weeks ]
    fMRI measure

  3. Implicit self-representations [ Time Frame: 1 day to 2 weeks ]
    Implicit Association Test

  4. Cognitive Flexibility [ Time Frame: 1 day to 2 weeks ]
    Neurocognitive testing


Secondary Outcome Measures :
  1. Quick Inventory of Depressive Symptoms [ Time Frame: 1 day to 2 weeks ]
    Self-reported depression

  2. Neural activation and connectivity patterns [ Time Frame: 1 day to 2 weeks ]
    fMRI measures

  3. Affective flexibility/inhibition [ Time Frame: 1 day to 2 weeks ]
    Neurocognitive testing

  4. Mood and Anxiety Symptom Questionnaire [ Time Frame: 1 day to 2 weeks ]
    Self-reported depression, anxiety, and distress

  5. Cognitive Triad Inventory [ Time Frame: 1 day to 2 weeks ]
    Negative perceptions of self, future, & world

  6. Columbia-Suicide Severity Rating Scale [ Time Frame: 1 day to lifetime ]
    Suicidality and patient safety

  7. WHO Disability Assessment Scale (SR) [ Time Frame: 1 to 30 days ]
    Global functioning

  8. Cognitive Flexibility Scale [ Time Frame: 1 day to lifetime ]
    Self-reported cognitive flexibility

  9. Neuroplasticity-related markers in blood [ Time Frame: 1 day to 2 weeks ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg).
  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, Azole antifungals, Erythromycin, HIV protease inhibitors
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03237286


Contacts
Contact: Rebecca B Price, PhD 4126486445 canlab@pitt.edu
Contact: Crystal Spotts, MEd 4122465764 spottsCR@upmc.edu

Locations
United States, Pennsylvania
Western Psychiatric Institute and Clinic Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Rebecca B Price, PhD    412-648-6445    canlab@pitt.edu   
Contact: Crystal Spotts    4122465764    spottscr@upmc.edu   
Sponsors and Collaborators
Rebecca Price
National Institute of Mental Health (NIMH)

Responsible Party: Rebecca Price, Assistant Professor of Psychiatry, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03237286     History of Changes
Other Study ID Numbers: 1R01MH113857 ( U.S. NIH Grant/Contract )
First Posted: August 2, 2017    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
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.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rebecca Price, University of Pittsburgh:
depression
ketamine
neurocognitive
fMRI
cognitive training

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action