Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression

• ClinicalTrials.gov Identifier: NCT03027362
• Recruitment Status: Completed
• First Posted: January 23, 2017
• Last Update Posted: February 5, 2020
• Sponsor: Yale University
• Information provided by (Responsible Party): Yale University

Tracking Information

• First Submitted Date: January 19, 2017
• First Posted Date: January 23, 2017
• Last Update Posted Date: February 5, 2020
• Actual Study Start Date: January 2017
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 20, 2017)

Time to relapse of depression measured by the Montgomery-Asberg Depressive Rating Scale (MADRS) score. [ Time Frame: Enrollment to 17 week follow-up ]

Relapse is defined as less than 50% improvement in MADRS compared to baseline MADRS score. The median time to relapse is the time at which the 50th percentile of participants relapses.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 20, 2017)

• Change in cognitive flexibility-working memory [ Time Frame: Before the first ketamine treatment and 24 hours following the last ketamine treatment. ]
  Measured by n-back task
• Change in cognitive flexibility-executive function [ Time Frame: Before the first ketamine treatment and 24 hours following the last ketamine treatment. ]
  Measured by set shifting task (COGSTATE test)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression
• Official Title: Cognitive Therapy to Sustain the Antidepressant Effects of Intravenous Ketamine in Treatment-resistant Depression: a Randomized Controlled Trial
• Brief Summary: The goals of this study are: 1) to investigate the efficacy of combining ketamine with intensive cognitive behavioral therapy (CBT) to sustain the antidepressant effects of ketamine; and 2) to determine ketamine's delayed effects on learning and memory, and to explore the relationship between any ketamine-induced changes in learning and memory and duration of antidepressant efficacy, with and without CBT augmentation. Subjects with a diagnosis of MDD who are treatment-resistant to at least 2 antidepressants and have chosen to pursue clinical ketamine treatment at Yale Psychiatric Hospital will be recruited for the study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Depressive Disorder, Major

Intervention

• Other: Cognitive behavioral therapy (CBT) and medication
  Sixteen sessions over 14 weeks.
• Other: Psychoeducation and medication

Study Arms

• Experimental: Cognitive behavioral therapy (CBT) and medication
  Following clinical ketamine treatment, the intervention includes sixteen CBT sessions over 14 weeks. In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or by a psychiatrist unaffiliated with the trial. Participants will remain on the medication they were prescribed when they entered the study and will be expected not to adjust the medication unless clinically urgent.
  Intervention: Other: Cognitive behavioral therapy (CBT) and medication
• Active Comparator: Psychoeducation and medication
  Following clinical ketamine treatment, the intervention includes psychoeducational sessions over 14 weeks.In addition, standard of care medications for treatment of depression, will be prescribed by the principal investigator or a by psychiatrist unaffiliated with the trial.
  Intervention: Other: Psychoeducation and medication

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 20, 2017): 28
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 15, 2020
• Actual Primary Completion Date: September 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Suffering from a major depressive episode based on Diagnostic and Statistical manual (DSM) 5 criteria and having failed one or more standard antidepressant treatments during the current episode
• Hamilton Depression Rating Scale (17-HAM-D) score of 21 or more prior to ketamine treatment.
• Planned clinical treatment with ketamine at Yale Psychiatric Hospital (YPH)
• As the purpose of this study is to determine the feasibility and efficacy of CBT to sustain the antidepressant effects of ketamine, only those who achieve a clinical response (i.e., 50% reduction in depression symptoms, as measured by the Montgomery-Asberg Depressive Rating Scale (MADRS) will be eligible for randomization.
• Patients must be treatment resistant to at least two drugs used to treat depression.

Exclusion Criteria:

• Any Axis I or Axis II Disorder, which at screening is clinically predominant to their depressive episode or has been predominant to their depressive episode at any time within 6 months prior to screening
• Active suicidal thoughts with a plan
• Current or recent (<6 months ago) substance use disorder
• Non-affective psychosis (such as schizophrenia or schizoaffective disorder)
• Inability to speak English fluently
• A clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results
• Dementia, delirium, or any other neurological or mental disease that might affect cognition or the ability to meaningfully participate in cognitive behavioral therapy (CBT).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03027362
• Other Study ID Numbers: 1609018450
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Yale University
• Original Responsible Party: Same as current
• Current Study Sponsor: Yale University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Samuel Wilkinson, MD; Yale University

• PRS Account: Yale University
• Verification Date: January 2020