Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention

Not Applicable

Recruiting

• Conditions: Depression and Suicide
• Interventions: Behavioral: Cognitive Behavioral Therapy CBT

• Registration Number: NCT04760652
• Lead Sponsor: Yale University

Brief Summary

This is a rater-blinded, randomized controlled trial. All patients will receive esketamine for treatment of Major Depression with Suicidal Ideation (MDSI). Subjects will be randomized (1:1) to receive CBT (computer-assisted) or TAU alone following esketamine.

Detailed Description

Specific Aim 1: To determine the feasibility and safety of performing a larger study examining the effectiveness and mechanism of action of CBT to improve the longer-term outcomes following esketamine treatment in patients hospitalized for suicidal ideation or suicide attempt.

Specific Aim 2: To evaluate the appropriateness and utility of the proposed tests of cognitive control measures in exploring the mechanisms underlying the effects on depression of esketamine and the combination of esketamine+CBT.

Specific Aim 3: To examine the efficacy of esketamine+CBT combination compared to esketamine+TAU in reducing suicidal ideation.

In August 2022, the targeted enrollment was expanded to include outpatient participants, the anticipated enrollment was increased from 60 to 100 participants as a result.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-02-04
• Study First Submitted QC: 2021-02-15
• Study First Posted: 2021-02-18
• Study Start: 2021-03-05
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-12
• Last Update Posted: 2024-07-16
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Participants are eligible for the study if they meet all the following criteria:

  1. Written informed consent before any study procedures are performed
  2. Meeting criteria for inpatient admission for suicidal ideation or attempt at one of the study sites
  3. Recommended by a physician for esketamine treatment
  4. Males or females ages 18 through 65 years of age
  5. Diagnosis of major depressive disorder as confirmed by the MINI (inpatient) or the HAM-D-17 (outpatient)
  6. Willing to adhere to a reliable form of contraception throughout the trial and for one month following completion of the trial (for subjects who are sexually active)
  7. In the opinion of the investigator, the patient is willing and able to comply with scheduled visits, treatment plan, and other trial procedures for the duration of the study

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Exclusion Criteria

• Participants are excluded if they meet any of the following criteria:

  1. Active substance use disorder (except tobacco) within 6 months of screening date

  2. Meets DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, or pervasive development disorder

  3. Dementia or other cognitive disorder or intellectual disability that would impair the subject's ability to meaningfully engage in CBT (per investigator judgment)

  4. Any other medical or psychiatric comorbidity that the investigator judges would put the participant at additional undue risk due to study participation or would impair subject's ability to participate in the study.

  5. Current or planned participation in a formal CBT program defined by the following characteristics, each session has an agenda, a homework assignment is given at each session, and the homework assignment from the previous session is reviewed at the following appointment.

  6. Previous Esketamine or ketamine treatment that did not produce a clinical response as outlined below.

     • 6 treatments with Esketamine at a dose of 56 mg or more with no clinical response
     • 6 treatments of IV ketamine at a dose between 0.4 mg/kg and 0.7mg /kg with no clinical response Patients must not have received Esketamine or ketamine treatment within the past 12 weeks of time of enrollment.

  7. The patient is pregnant or breastfeeding

  8. Unable to give informed consent

  9. Was previously enrolled/randomized into the trial

  10. Patients who have a contraindication to receiving Esketamine including any of the following:

      • aneurysmal vascular disease
      • arteriovenous malformation
      • history of intracerebral hemorrhage
      • hypersensitivity to esketamine or ketamine

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAU Treatment As Usual	Cognitive Behavioral Therapy CBT	Participants will undergo Treatment as usual (TAU). These patients will undergo standard, post-hospitalization clinical treatments, which many include physician visits and psychotherapy (except for formal CBT).
CBT Cognitive Behavioral Therapy	Cognitive Behavioral Therapy CBT	Participants will receive CBT, which will consist of in-person and computer-based component (based on Good Days Ahead). This will consist of 20 sessions given over 16 weeks.

Primary Outcome Measures

Name	Time	Method
To determine the feasibility of performing a larger study with similar design by measuring attrition.	Attrition will be assessed at 18 months.	Feasibility will be evaluated by measures of attrition rates by attaining 80% of retention will of 70% of participants will be considered feasible.
Evaluate the appropriateness of the proposed tests of cognitive control measures in exploring the mechanisms of change.	The appropriateness will be assessed at the end of study (18 months).	Appropriateness will be evaluated by the proportion of patients who are able to complete the cognitive control assessments. As this is a feasibility study, we do not have pre-specified quantitative cutoffs.
To determine the feasibility of performing a larger study with similar design by measuring of recruitment rates.	Recruitment rates will be assessed at 18 months.	Feasibility will be evaluated by measures of recruitment rates measured by attaining 80% of recruitment target will be considered feasible.
Reasons for discontinuation	Discontinuation will be assessed at 18 months.	Feasibility will be evaluated by measures of reasons for discontinuation regardless of clinical state, to Week 18 or later will be considered feasible.
To determine the safety of performing a larger study with similar design.	Safety will be assessed at 18 months.	Safety will be evaluated by measures of the number by type of protocol deviations.

Secondary Outcome Measures

Name	Time	Method
Efficacy of esketamine/CBT combination compared to esketamine/TAU in reducing the risk of suicide.	Measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary observation will be the last observation carried forward per protocol at Week 18.	Efficacy will be measured by the response to the MADRS (Montgomery-Asberg Depression Rating Scale). The MADRS is a 10 question assessments conducted in an interview setting.

Trial Locations

Locations (3)

UAB Medicine | Heersink School of Medicine; 🇺🇸 Birmingham, Alabama, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States