Clinical trial NCT04760652: Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention
Official title: CBT-ENDURE: Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Depression and Suicide
Keywords: Depression
Suicide
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2021-02-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Esketamine:All participants will receive esketamine for MDSI (Major depression with suicidal ideation) as part of their standard care. The protocol will adhere to the FDA label for this product and the FDA-registered trials.

CBT:Half of participants will be randomized to the CBT intervention, which will consist of an in-person and computer-based component (based on Good Days Ahead). In total, this will consist of 20 total sessions given over 16 weeks (the first 4 weeks of CBT will have sessions twice weekly; thereafter sessions will be held weekly).

TAU only:Participants not randomized to CBT will undergo treatment as usual (TAU). These patients will undergo standard, post-hospitalization clinical treatments, which may include physician visits and psychotherapy (except for formal CBT).
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: To determine the feasibility of performing a larger study with similar design by measuring of recruitment rates.
timeFrame: Recruitment rates will be assessed at 18 months.
measure: To determine the feasibility of performing a larger study with similar design by measuring attrition.
timeFrame: Attrition will be assessed at 18 months.
measure: Reasons for discontinuation
timeFrame: Discontinuation will be assessed at 18 months.
measure: To determine the safety of performing a larger study with similar design.
timeFrame: Safety will be assessed at 18 months.
measure: Evaluate the appropriateness of the proposed tests of cognitive control measures in exploring the mechanisms of change.
timeFrame: The appropriateness will be assessed at the end of study (18 months).
Secondary outcomes:
measure: Efficacy of esketamine/CBT combination compared to esketamine/TAU in reducing the risk of suicide.
timeFrame: 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.
Other outcomes:
measure: To evaluate the depression assessments BDI-II (Beck Depression Inventory).
timeFrame: BDI-II will be measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary assessment of this outcome will be at Week 18.
measure: To evaluate the depression assessments CGI (Clinical Global Impression for Severity of Suicidality).
timeFrame: CGI will be measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary assessment of this outcome will be at Week 18.
measure: To evaluate the Suicide Ideation assessments CSSRS (COLUMBIA-SUICIDE SEVERITY RATING SCALE).
timeFrame: The CSSRS will be measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary assessment of this outcome will be at Week 18.
measure: To evaluate the BSI (Beck Scale for Suicidal Ideation).
timeFrame: The BSI will be measured at Baseline, study day 2, study day 15, study day 30, weeks 7 - 17, week 18, week 26. The primary assessment of this outcome will be at Week 18.
measure: To evaluate the RRS (Ruminative Responses Scale).
timeFrame: We will compare at Week 18 using last observation carried forward per protocol.
measure: To evaluate the SoCT (Skills of Cognitive Therapy.
timeFrame: We will compare at Week 18 using last observation carried forward per protocol.
measure: To evaluate CTAS (Computer-Assisted Cognitive-Behavior Therapy for Depression).
timeFrame: We will compare at Week 18 using last observation carried forward per protocol.
Locations:
city: Birmingham
country: United States
facility: UAB Medicine | Heersink School of Medicine
state: Alabama
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
Study officials:
affiliation: Yale University
name: Samuel T Wilkinson, MD
role: PRINCIPAL_INVESTIGATOR
References: