A Study to Assess Feasibility of Using Clinician-directed and Digital Application Supported Cognitive Behavior Therapy (CBT) in Conjunction With Esketamine in Participants With Treatment-resistant Depression

Assessment of Feasibility of Using Clinician-Directed Cognitive Behavior Therapy Supplemented by a Digital Application in Conjunction With Esketamine (SPRAVATO®) in Participants With Treatment-Resistant Depression

The purpose of this study is to explore feasibility of combining clinician-directed cognitive behavioral therapy (CBT) supplemented with the Mindset app with esketamine therapy in participants with Treatment-resistant Depression.

Study Overview

• Status: Withdrawn
• Conditions: Depression
• Intervention / Treatment: Drug: Esketamine; Behavioral: Cognitive Behavioral Therapy (CBT); Drug: Antidepressant

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University Of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Sheppard Pratt Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati, Dept of Psychiatry & Behavioral Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Medically stable on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening. Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant's source documents and initialed by the investigator
• Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features, based upon clinical assessment confirmed by the Mini International Neuropsychiatric Interview (MINI)
• Participant must have had nonresponse to greater than or equal to (>=) 2 different oral antidepressant treatments of adequate dose and duration in the current episode of depression
• Participant must be currently taking an oral antidepressant.
• Participant must be comfortable with self-administration of nasal spray medication and be able to follow the nasal spray administration instructions provided

Exclusion Criteria:

• Participant's depressive symptoms have previously demonstrated nonresponse to an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
• Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
• Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of the screening phase. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary
• Participant has any anatomical or medical condition that, per the investigator's clinical judgment based on assessment, may impede delivery or absorption of nasal spray study drug
• Participant has known allergies, hypersensitivity, intolerance, or contraindications to esketamine/ketamine and/or its excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Esketamine; Participants will receive esketamine nasal spray (Dose 1 or Dose 2) twice weekly for 4 weeks (Induction Phase), followed by once a week dose (Dose 1 or Dose 2) for 8 weeks (Maintenance Phase), in conjunction with an oral antidepressant. Clinician-directed cognitive behavioral therapy (CBT) supplemented with the Mindset app will be administered by a clinician following esketamine dosing once the participants is considered ready to engage in therapy, based on the clinician judgement of CBT readiness.

Drug: Esketamine; Esketamine will be self-administered as nasal spray.; Other Names: JNJ-54135419; SPRAVATO; Non-Investigational Medicinal Product/Auxiliary Medicinal Product (NIMP/AxMP); Behavioral: Cognitive Behavioral Therapy (CBT); Clinician-directed CBT supplemented by the Mindset app will be administered.; Drug: Antidepressant; Antidepressant will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
System Usability Scale (SUS) Scores (Participants)	The SUS provides a reliable tool for measuring the usability of a wide variety of products and services, including hardware, software, mobile devices, websites, and applications. It consists of a 10-item questionnaire with five response options for respondents; from strongly agree to strongly disagree.	Week 13
Net Promoter Scale Scores (Participants)	Net promoter score is a market research measure that asks respondents to rate the likelihood that they would recommend a company, product, or a service to a friend or colleague. Responses are on a rating on a scale of 0 (not at all likely) to 10 (extremely likely).	Week 13
Exit Survey	Exit survey is a survey including ratings regarding participant impression of features of the Mindset app.	Week 13
Time Spent on Mindset App	Time spent on Mindset app will be reported for participants.	From Week 2 up to Week 13
Number of Times Mindset App Used	Number of times the Mindset app is used will be reported.	From Week 2 up to Week 13
Pattern of Mindset App Used	Pattern of Mindset app usage will be reported.	From Week 2 up to Week 13
CBT Therapist Assessment of Completion of Action Plan	Assessment of completion of action plan will be done by CBT therapists through rating on a 5-point likert scale of the participant's progress.	From Week 2 up to Week 13
Participant Interviews	Optional qualitative feedback from study participants (participant's interviews) on the usefulness of the Mindset in conjunction with esketamine will be reported.	Week 20
SUS Scores (CBT Therapists)	The SUS provides a reliable tool for measuring the usability of a wide variety of products and services, including hardware, software, mobile devices, websites, and applications. It consists of a 10-item questionnaire with five response options for respondents; from strongly agree to strongly disagree.	Up to 14 months (at the end of study)
Net Promoter Scale Scores (CBT Therapists)	Net promoter score is a market research measure that asks respondents to rate the likelihood that they would recommend a company, product, or a service to a friend or colleague. Responses are on a rating on a scale of 0 (not at all likely) to 10 (extremely likely).	Up to 14 months (at the end of study)
Frequency of Use of Clinician Dashboard Used	Frequency of use of clinician dashboard will be reported.	From Week 2 up to Week 13
Clinician Feedback	Qualitative feedback on clinician dashboard and participant use of the mindset app in conjunction with esketamine (clinician feedback) will be reported.	Up to 14 months
Percentage of Participants Able to Engage in CBT	Percentage of participants able to engage in CBT on the day of dosing for each week of the study and overall will be reported.	From Week 2 up to Week 13
Timing of CBT Readiness after Dosing	Timing of CBT readiness after dosing will be reported. Determination of readiness will be based on clinician judgement of CBT readiness to engage in CBT based on alertness and ability to concentrate after dosing.	From Week 2 up to Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Scale Score	The MOAA/S will be used to measure treatment-emergent sedation with correlation to levels of sedation defined by the American Society of Anesthesiologists (ASA) continuum. The MOAA/S scores range from 0=no response to painful stimulus (corresponds to ASA continuum for general anesthesia) to 5=readily responds to name spoken in normal tone (awake; corresponds to ASA continuum for minimal sedation).	Pre-dose, 40 minutes and 90 minutes post-dose up to Week 4
Clinician Administered Dissociative States Scale (CADSS) Score	The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. The CADSS consists of 23 subjective items, divided into 3 components: depersonalization (Items 3 to 7, 20, and 23), derealization (Items 1, 2, 8 to 13, 16 to 19, and 21) and amnesia (Items 14, 15, and 22). Participant's responses are coded on a 5-point scale (0=not at all through to 4=extremely). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition	Pre-dose, 40 minutes and 90 minutes post-dose up to Week 4
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Number of participants with TEAEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment	From Week 2 up to Week 13
Number of Participants with Abnormalities in Vital Signs	Number of participants with abnormalities in vital signs (pulse/heart rate, blood pressure, and body temperature) will be reported.	From Week 2 up to Week 13
Columbia Suicide Severity Rating (C-SSRS) Score	C-SSRS is semi structured clinician-administered questionnaire designed to solicit the occurrence, severity, and frequency of suicide-related ideation and behaviors. The maximum score assigned for each participant will also be summarized into one of three categories: no suicidal ideation or behavior (0), suicidal ideation (1-5), suicidal behavior (6-10). Total score ranges from 1 to 10. Higher scores indicate greater severity.	Up to Week 13
Clinical Global Assessment of Discharge Readiness (CGADR) Score	The CGADR will be used to measure the participant's current clinical status and is the clinician's assessment of the readiness to be discharged from the study site. The clinician will answer "Yes" or "No" to the question "Is the participant considered ready to be discharged based on their overall clinical status (example, sedation, blood pressure, and other adverse events)?"	From Week 2 up to Week 13

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2022
• Primary Completion (Estimated): June 7, 2023
• Study Completion (Estimated): June 7, 2023

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (Actual): March 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Psychotropic Drugs; Esketamine; Antidepressive Agents
• Other Study ID Numbers: CR109113; NATRD1001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No