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

Primary Purpose

Depression and Suicide

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cognitive Behavioral Therapy CBT
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression and Suicide focused on measuring Depression, Suicide

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UAB Medicine | Heersink School of MedicineRecruiting
  • Yale UniversityRecruiting
  • Emory UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

CBT Cognitive Behavioral Therapy

TAU Treatment As Usual

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

To determine the feasibility of performing a larger study with similar design by measuring of recruitment rates.
Feasibility will be evaluated by measures of recruitment rates measured by attaining 80% of recruitment target will be considered feasible.
To determine the feasibility of performing a larger study with similar design by measuring attrition.
Feasibility will be evaluated by measures of attrition rates by attaining 80% of retention will of 70% of participants will be considered feasible.
Reasons for discontinuation
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 evaluated by measures of the number by type of protocol deviations.
Evaluate the appropriateness of the proposed tests of cognitive control measures in exploring the mechanisms of change.
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.

Secondary Outcome Measures

Efficacy of esketamine/CBT combination compared to esketamine/TAU in reducing the risk of suicide.
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.

Full Information

First Posted
February 4, 2021
Last Updated
September 18, 2023
Sponsor
Yale University
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT04760652
Brief Title
Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention
Acronym
ENDURE
Official Title
CBT-ENDURE: Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 5, 2021 (Actual)
Primary Completion Date
August 31, 2024 (Anticipated)
Study Completion Date
August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression and Suicide
Keywords
Depression, Suicide

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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).
Masking
Outcomes Assessor
Masking Description
Rater blinded
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CBT Cognitive Behavioral Therapy
Arm Type
Active Comparator
Arm Description
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.
Arm Title
TAU Treatment As Usual
Arm Type
Other
Arm Description
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).
Intervention Type
Behavioral
Intervention Name(s)
Cognitive Behavioral Therapy CBT
Intervention Description
CBT: In-person and computer-based components (Good Days Ahead) First 4 weeks of CBT are twice weekly; thereafter weekly CBT
Primary Outcome Measure Information:
Title
To determine the feasibility of performing a larger study with similar design by measuring of recruitment rates.
Description
Feasibility will be evaluated by measures of recruitment rates measured by attaining 80% of recruitment target will be considered feasible.
Time Frame
Recruitment rates will be assessed at 18 months.
Title
To determine the feasibility of performing a larger study with similar design by measuring attrition.
Description
Feasibility will be evaluated by measures of attrition rates by attaining 80% of retention will of 70% of participants will be considered feasible.
Time Frame
Attrition will be assessed at 18 months.
Title
Reasons for discontinuation
Description
Feasibility will be evaluated by measures of reasons for discontinuation regardless of clinical state, to Week 18 or later will be considered feasible.
Time Frame
Discontinuation will be assessed at 18 months.
Title
To determine the safety of performing a larger study with similar design.
Description
Safety will be evaluated by measures of the number by type of protocol deviations.
Time Frame
Safety will be assessed at 18 months.
Title
Evaluate the appropriateness of the proposed tests of cognitive control measures in exploring the mechanisms of change.
Description
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.
Time Frame
The appropriateness will be assessed at the end of study (18 months).
Secondary Outcome Measure Information:
Title
Efficacy of esketamine/CBT combination compared to esketamine/TAU in reducing the risk of suicide.
Description
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.
Time Frame
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 Pre-specified Outcome Measures:
Title
To evaluate the depression assessments BDI-II (Beck Depression Inventory).
Description
The BDI-II range of values is 0-42 and the clinical interpretation are indicated with higher scores indicating greater severity of illness.
Time Frame
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.
Title
To evaluate the depression assessments CGI (Clinical Global Impression for Severity of Suicidality).
Description
The CGI range of values is 1-5 and the clinical interpretation is indicated with higher scores indicating greater severity of illness.
Time Frame
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.
Title
To evaluate the Suicide Ideation assessments CSSRS (COLUMBIA-SUICIDE SEVERITY RATING SCALE).
Description
The CSSRS range of values 0-5 and the clinical interpretation is indicated with higher score indicating greater severity.
Time Frame
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.
Title
To evaluate the BSI (Beck Scale for Suicidal Ideation).
Description
The BSI range of values 0-63 and the clinical interpretation is indicated with higher scores indicating greater severity of illness.
Time Frame
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.
Title
To evaluate the RRS (Ruminative Responses Scale).
Description
RRS range of values is 22-88, with higher scores indicating greater severity.
Time Frame
We will compare at Week 18 using last observation carried forward per protocol.
Title
To evaluate the SoCT (Skills of Cognitive Therapy.
Description
SoCT range of values is 8-40, with higher scores indicating greater mastery of CBT.
Time Frame
We will compare at Week 18 using last observation carried forward per protocol.
Title
To evaluate CTAS (Computer-Assisted Cognitive-Behavior Therapy for Depression).
Description
CTAS range of values is 0-40, with higher scores indicating greater knowledge of CBT.
Time Frame
We will compare at Week 18 using last observation carried forward per protocol.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participants are eligible for the study if they meet all the following criteria: Written informed consent before any study procedures are performed Meeting criteria for inpatient admission for suicidal ideation or attempt at one of the study sites Recommended by a physician for esketamine treatment Males or females ages 18 through 65 years of age Diagnosis of major depressive disorder as confirmed by the MINI (inpatient) or the HAM-D-17 (outpatient) 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) 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: Active substance use disorder (except tobacco) within 6 months of screening date Meets DSM-5 criteria for bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, or pervasive development disorder Dementia or other cognitive disorder or intellectual disability that would impair the subject's ability to meaningfully engage in CBT (per investigator judgment) 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. 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. 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. The patient is pregnant or breastfeeding Unable to give informed consent Was previously enrolled/randomized into the trial 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cindy Voghell
Phone
203-764-9131
Email
cynthia.voghell@yale.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Julie Holub
Phone
203-764-9131
Email
julie.holub@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samuel T Wilkinson, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
UAB Medicine | Heersink School of Medicine
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samantha White, BS, CCRC
Phone
205-934-9189
Email
swwhite@uabmc.edu
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cindy Voghell
Email
cynthia.voghell@yale.edu
First Name & Middle Initial & Last Name & Degree
Julie Holub
Phone
(475) 306-4188
Email
julie.holub@yale.edu
First Name & Middle Initial & Last Name & Degree
Samuel T Wilkinson, MD
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Valeriya C Tsygankova
Phone
404-712-6947
Email
vtsygan@emory.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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

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