Intravenous Ketamine Plus Neurocognitive Training for Depression

Sponsor

Rebecca Price (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03237286

Collaborator

National Institute of Mental Health (NIMH) (NIH)

154

Enrollment

Location

Arms

59.5

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:

Interventional

Actual Enrollment :

154 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 :

Dec 1, 2017

Anticipated Primary Completion Date :

Nov 15, 2022

Anticipated Study Completion Date :

Nov 15, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Montgomery Asberg Depression Scale [1 day to 2 weeks]
Clinician-rated depression
Executive-salience network functional connectivity [1 day to 2 weeks]
fMRI measure
Implicit self-representations [1 day to 2 weeks]
Implicit Association Test
Cognitive Flexibility [1 day to 2 weeks]
Neurocognitive testing
Quick Inventory of Depressive Symptoms [1 day to 2 weeks]
Self-reported depression

Secondary Outcome Measures

Neural activation and connectivity patterns [1 day to 2 weeks]
fMRI measures
Affective flexibility/inhibition [1 day to 2 weeks]
Neurocognitive testing
PROMIS measures-depression [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 [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 [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 [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 [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 [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 [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 [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 [1 day to 2 weeks]
Negative perceptions of self, future, & world
Columbia-Suicide Severity Rating Scale [1 day to lifetime]
Suicidality and patient safety
WHO Disability Assessment Scale (SR) [1 to 30 days]
Global functioning
Cognitive Flexibility Scale [1 day to lifetime]
Self-reported cognitive flexibility
Neuroplasticity-related markers in blood [1 day to 2 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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
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.
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
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.
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.
Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening. Birth control is not an exclusion.
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