KET-RO Plus RO DBT for Treatment Resistant Depression (KET-RO)

Medication-assisted Psychotherapy: Using Ketamine-enhanced Radically Open Dialectical Behavior Therapy (RO DBT) to Target Neural and Behavioral Mechanisms of Action in Adults With Moderate to Severe Depression

This pilot study will assess the safety and feasibility of intravenous (IV) ketamine combined with RO DBT in young adults with Treatment-Resistant Depression (TRD). In addition, this study will develop and utilize innovative methodological approaches to demonstrate the feasibility of precision medicine with this type of therapy.

Study Overview

• Status: Completed
• Conditions: Treatment Resistant Depression
• Intervention / Treatment: Combination product: Ketamine Infusion plus RO DBT

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Males and females aged 18-65
• Moderate to severe persistent depression [treatment resistant depression - TRD] (exhibiting 2+ unipolar major depression episodes (non-delusional) with prior treatment non-response to antidepressant or psychosocial treatment
• Treatment-resistant depression: defined as unipolar major depressive disorder, non-delusional (diagnosed by SCID-5, Structured Clinical Interview for the DSM ) that persists despite ≥ 2 adequate antidepressant trials of different classes in the current episode; including at least one evidence-based second-line treatment in the current episode (including serotonin norepinephrine reuptake inhibitors, bupropion, tricyclics, monoamine oxidase inhibitors, or augmentation with an atypical antipsychotic, stimulant, bupropion, lithium, or Triiodothyroinine) higher proportion of OC (over controlled) words endorsed compared to UC (Under controlled) words on the Word Pairs Checklist
• no current or past psychosis
• English speaking
• Able to attend in-person behavioral sessions and ketamine/therapy visits
• Willingness to have RO DBT-A as only psychosocial treatment engaged in (medication treatment may continue-but see below for exclusion)

Exclusion Criteria:

• Outside age range
• Significant neurological condition (i.e., seizure, stroke, severe head injury) or mental retardation (IQ<70)
• Current or recent substance use disorder, actively suicidal or homicidal (e.g., requires hospitalization)
• Use of naltrexone, memantine or medication considered contraindicated with ketamine
• Baseline systolic BP > 150 systolic or 90 diastolic at evaluation. Participants who initially present with elevated blood pressure may be re-assessed; and if needed, referred to their healthcare provider for hypertension management
• Taking more than 2 adequately-dosed oral antidepressants
• Inability to understand, speak and read English sufficiently
• Not be pregnant or at risk of becoming pregnant
• Medical conditions or medication usage that in the judgement of the investigators puts the patient at unreasonable safety risk
• First degree relative with a psychotic diagnosis involving hallucinations, delusions, or disorganized thinking and speech (e.g. schizophrenia, schizoaffective disorder, etc)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine Infusion	Combination product: Ketamine Infusion plus RO DBT; The participant will receive 4 weeks of 0.5mg/kg intravenous ketamine given over 40 minutes, as is routinely done in ketamine treatment and four months of RO DBT treatment.
Experimental: Radically Open Dialectical Behavior Therapy (RO DBT)	Combination product: Ketamine Infusion plus RO DBT; The participant will receive 4 weeks of 0.5mg/kg intravenous ketamine given over 40 minutes, as is routinely done in ketamine treatment and four months of RO DBT treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Depressive Symptoms	Decrease in depressive symptoms as assessed via the Montgomery and Asberg Depression Rating Scale (MADRS), a clinician-interviewed assessment of depressive symtpoms. Scale ranges from 0-60 with higher scores indicating higher depression severity.	Approximately 5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale (VAS) of Depressive and Anxiety Symptoms	Visual analogue sliding scale (0-100) of self-reported ratings of feeling "depressed" or "anxious" in the moment, with higher scores indicating higher depression or anxiety. This visual analogue scale was administered three times: pre-ketamine, 40 minutes post-ketamine and 90 minutes post-ketamine. Reported below is the average rating across all ketamine sessions across the 4 weeks at the 90 minute post-ketamine reported. Units of measure are on the 0 to 100 scale.	Completed immediately following individual ketamine sessions during 4 weeks of ketamine-assisted RO DBT
Reward Positivity (RewP)	The Reward Positivity (RewP) is an electroencephalogram (EEG) based event related potential (ERP) and neural marker of reward responding. During the "Doors Task", a commonly used task to elicit the RewP, participants can win money or lose money when opening doors. The RewP is calculated as the electrical signal in response to winning at electrode Cz on the scalp minus the electrical signal in response to losing at electrode Cz between the timepoints 250-500ms. Thus, it is a difference score of win minus loss response to assess reward response and is measured via microvolts with higher scores indicating a stronger neural response to reward. It will examine change mid-treatment (Post Ketamine) and post treatment. Post-treatment RewP scores reported below.	Immediately post-treatment (approximately 5 months since baseline)
Error-related Negativity (ERN)	The erorr-related negativity (ERN) is an electroencephalogram (EEG) based neural marker of error monitoring measured via an event related potential (ERP). It is elicited via Go/No-go tasks where participants make 'correct' responses and 'error' responses. The ERN is calculated as the electrical signal in response to making an error response at Cz on the scalp minus the electrical signal in response to making a correct response at electrode Cz between timepoints 0-50ms. Thus, it is a difference score of error - correct neurla response to assess error or performance monitoring and is measured via microvolts with higher scores indicating a larger response to errors. It will examine change mid-treatment (post ketamine) and post-treatment. Post-treatment ERN scores reported below.	Immediately post-treatment (approximately 5 months since baseline)
Social Connectedness Scale- Revised (SCS-R)	The Social Connectedness Scale Revised (SCS-R) is a self-report that assesses interpersonal closeness with a range of scores from 20 to 120, with a higher total score indicating greater social connectedness. This measure will examine mechanistic change mid-treatment (post ketamine) and post-treatment; Post-treatment scores provided below.	Immediately post-treatment (approximately 5 months since baseline)
UCLA Loneliness Scale	The UCLA loneliness scale measure social connectedness (or lack of given it assesses perceived loneliness) via self-report with a range of 20 to 80 with higher scores indicating greater loneliness. This measure will examine mechanistic change mid-treatment (post ketamine) and post-treatment; Post-treatment scores provided below.	Immediately post-treatment (approximately 5 months since baseline)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal Experience of Pleasure Scale (TEPS)	The Temporal Experience of Pleasure Scale (TEPS) is a self-report behavioral assessment. This measure assesses anticipatory pleasure and consummatory or outcome pleasure of reward responding into a total score of reward responding, with scores ranging from 18 to 108 with higher scores indicating greater capacity for pleasure and reward. It will examine mechanistic change mid-treatment (post ketamine) and post-treatment; post-treatment scores reported below.	Immediately post-treatment (approximately 5 months since baseline)
Acceptance and Action Questionnaire--II (AAQ-II)	The Acceptanc and Action Qustionnaire-II (AAQ-II) is a self-reported beahvioral measure of psychological inflexibility with scores ranging from 7 to 49, with higher scores indicating greater psychological inflexibility. It will examine mechanistic change mid-treatment (post-ketamine) and post-treatment; post-treatment scores provided below.	Immediately post-treatment (approximately 5 months since baseline)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Kirsten Gilbert, PhD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2023
• Primary Completion (Actual): January 11, 2025
• Study Completion (Actual): February 22, 2025

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 202212113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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