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

Depression and Suicide Clinical Trial

— ENDURE  

Official title:

CBT-ENDURE: Cognitive Behavioral Therapy Following Esketamine for Major Depression and Suicidal Ideation for Relapse Prevention

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04760652
• Other study ID #: 2000029473
• Secondary ID: 12657361691R01MH
• Status: Recruiting
• Phase: N/A
• Start date: March 5, 2021
• Est. completion date: August 31, 2024

Study information

• Verified date: September 2023
• Source: Yale University
• Contact: Cindy Voghell
• Phone: 203-764-9131
• Email: cynthia.voghell[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depression and Suicide
• Depressive Disorder
• Suicidal Ideation
• Suicide

Intervention

Behavioral:
• Cognitive Behavioral Therapy CBT
CBT: In-person and computer-based components (Good Days Ahead) First 4 weeks of CBT are twice weekly; thereafter weekly CBT

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	UAB Medicine | Heersink School of Medicine	Birmingham	Alabama
United States	Yale University	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To evaluate the depression assessments BDI-II (Beck Depression Inventory).	The BDI-II range of values is 0-42 and the clinical interpretation are indicated with higher scores indicating greater severity of illness.	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.
Other	To evaluate the depression assessments CGI (Clinical Global Impression for Severity of Suicidality).	The CGI range of values is 1-5 and the clinical interpretation is indicated with higher scores indicating greater severity of illness.	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.
Other	To evaluate the Suicide Ideation assessments CSSRS (COLUMBIA-SUICIDE SEVERITY RATING SCALE).	The CSSRS range of values 0-5 and the clinical interpretation is indicated with higher score indicating greater severity.	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.
Other	To evaluate the BSI (Beck Scale for Suicidal Ideation).	The BSI range of values 0-63 and the clinical interpretation is indicated with higher scores indicating greater severity of illness.	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.
Other	To evaluate the RRS (Ruminative Responses Scale).	RRS range of values is 22-88, with higher scores indicating greater severity.	We will compare at Week 18 using last observation carried forward per protocol.
Other	To evaluate the SoCT (Skills of Cognitive Therapy.	SoCT range of values is 8-40, with higher scores indicating greater mastery of CBT.	We will compare at Week 18 using last observation carried forward per protocol.
Other	To evaluate CTAS (Computer-Assisted Cognitive-Behavior Therapy for Depression).	CTAS range of values is 0-40, with higher scores indicating greater knowledge of CBT.	We will compare at Week 18 using last observation carried forward per protocol.
Primary	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.	Recruitment rates will be assessed at 18 months.
Primary	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.	Attrition will be assessed at 18 months.
Primary	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.	Discontinuation will be assessed at 18 months.
Primary	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.	Safety will be assessed at 18 months.
Primary	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.	The appropriateness will be assessed at the end of study (18 months).
Secondary	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.	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.