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

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Uchechukwu Agali, BS; Phone Number: (314) 286-0788; Email: agali@wustl.edu
• Study Contact Backup: Name: Teresa Perryman, BA; Phone Number: 3142860965; Email: tperryman@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1010
      • Recruiting
      • Washington University School of Medicine
      • Contact: Kirsten Gilbert, PhD; Phone Number: 314-747-0001; Email: gilbertk@wustl.edu

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
Remission from Depression	Remission defined as Montgomery and Asberg Depression Rating Scale (MADRS) score ≤10. 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 of depressive and anxiety symptoms	Asses daily changes in symptoms following ketamine infusions and RODBT sessions	Daily following ketamine and therapy sessions during 4 weeks of ketamine-assisted RO DBT
RewP	The RewP is a neural marker of reward responding and is EEG based. It will examine change id-treatment (Post Ketamine) and post treatment	Approximately 5 months
ERN	The ERN is a neural marker of error monitoring and is EEG based. It will examine mechanistic change mid-treatment (post ketamine) and post-treatment.	Approximately 5 months
SCS-R and UCLA Loneliness Scale	The Social Connectedness SCale Revised (SCS-R) and the UCLA loneliness scale measure social connectedness (or lack of) via self-report. They will examine mechanistic change mid-treatment (post ketamine) and post-treatment.	Approximately 5 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal Experience of Pleasure Scale (TEPS)	The TEPS is a self-report behavioral assessment, This measure assesses anticipatory pleasure and consummatory or outcome pleasure of reward responding. It will examine mechanistic change mid-treatment (post ketamine) and post-treatment.	Approximately 5 months
Action and Acceptance Questionnaire (AAQ)	The AAQ is a self-reported beahvioral measure of psychological flexibility. It will examine mechanistic change mid-treatment (post-ketamine) and post-treatment.	Approximately 5 months

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 (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 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 (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; 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