KAP for Depression in Abstinent Opioid Users (KReDO)

Ketamine-assisted Psychotherapy for the Treatment of Persistent Depression in Abstinent Opioid Users

The purpose of the study is to examine whether an investigational medication called ketamine along with psychotherapy is an effective treatment for depression in participants with a history of opioid addiction who have not abused opioids in at least 3 months. Participants will receive ketamine through intramuscular injection along with psychotherapy weekly for 8 weeks. Participation for eligible subjects who decide to enroll (including post-medication follow-up visits) will last about 16 weeks or 4 months.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder; Opioid Use Disorder, Severe, in Sustained Remission; Opioid Use Disorder, Severe, in Early Remission
• Intervention / Treatment: Drug: Ketamine-assisted psychotherapy

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina Centerspace

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

A subject may be eligible for enrollment if all the following inclusion criteria apply within the thirty days prior to first experimental session:

1. Between the ages of 18 to 64 years old.
2. Able to provide informed consent.
3. Meet DSM-5 criteria for Major Depressive Disorder, without psychotic features based on clinical interview.
4. Score at least 20 on the Montgomery-Asberg Depression Rating Scale (MADRS, moderate or severe depression).
5. Must meet criteria for opioid use disorder in early or sustained remission criteria by DSM-5 based on clinical interview.
6. Subjects taking other psychotropic medications (e.g. anti-depressants, anxiolytics, methadone, buprenorphine, naltrexone) must be maintained on a stable dose for at least four weeks before study initiation.

Exclusion Criteria

Subjects will be excluded from the study if any of the following criteria apply:

1. They are considered an immediate suicide risk by clinician assessment, self-reports a suicide attempt within the past year, or felt to be likely to require hospitalization during the study.
2. Subjects who meet DSM-5 criteria for current bipolar disorder based on clinical interview.
3. Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders based on clinical interview.
4. Subjects meeting DSM-5 criteria for current substance use disorder (i.e., not in early or sustained remission) other than tobacco use disorder.
5. Subjects who report use of ketamine >20 times in the past or who meet DSM-5 criteria for Other Hallucinogen Use Disorder due to ketamine use including subjects who are currently in early or sustained remission.
6. Women who are pregnant or nursing, and women who do not consent to use methods of highly effective birth control during the interventional phase of the study.
7. Subjects with hypertension as defined by a baseline visit systolic blood pressure (SBP) >140 mmHg or a diastolic blood pressure (DBP) >90 mmHg.
8. A history of allergic or other adverse reaction to ketamine (or its excipients).
9. Clinically significant physical exam findings or self-reported medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g. glaucoma, aneurysmal disease, cardiovascular disease, or end-stage renal disease).
10. QTc will be measured in all subjects and those with QTc 450ms or longer will be excluded.
11. Subjects who live greater than 20 miles from the study site and cannot arrange their own transportation will be excluded from the study.
12. Subjects with kidney or liver impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Ketamine-assisted psychotherapy; Subjects will receive 8 weekly intramuscular injections of ketamine hydrochloride starting at 0.5 mg/kg and increasing to a maximum dose of 1.5 mg/kg or a total dose of 60 mg, whichever is lower. Ketamine administration will be accompanied by psychotherapy before, after and during the session.	Drug: Ketamine-assisted psychotherapy; Subjects will receive 8 weekly intramuscular injections of ketamine hydrochloride starting at 0.5 mg/kg and increasing to a maximum dose of 1.5 mg/kg or a total dose of 60 mg, whichever is lower. Ketamine administration will be accompanied by psychotherapy before, after and during the session.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Asberg Depression Rating Scale	Montgomery Asberg Depression Rating Scale (MADRS). The MADRS is a clinician administered, 10-item questionnaire of depression severity. The total score ranges from 0-60, with scores of 0-6 considered normal (non-depressed), 7-19 indicative of mild depression, 20-34 indicative of moderate depression, and 35-60 indicative of severe depression. Individuals scoring 20 or higher on the MADRS will be included in the study. The MADRS evaluates the following symptoms of depression: 1) clinical appearance of sadness, 2) self-reported sadness, 3) inner tension, 4) reduced sleep, 5) reduced appetite, 6) concentration difficulties, 7) lassitude, 8) inability to feel, 9) pessimistic thought process, and 10) thoughts of suicide. Lower scores are better (less depression).	Change from baseline measured at week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beck Depression Inventory	Self-rated depression inventory; minimum score of 0 maximum score of 63 with lower scores being a better outcome (less depressed)	Change from baseline measured at week 1-9, 10, 12, and 16
Timeline Follow-back (TLFB)	Measure of Substance Use; maximum number of substance use days per week is 7 and minimum is 0 with higher number indicating worse outcomes (more substance use)	Measured at week 1-9, 10, 12, and 16
Visual Analog Scale (VAS)	Measure of subjective level of opioid craving; maximum score of 100 and minimum score of 0 with higher scores meaning worse outcome (more cravings)	Change relative to baseline measured at week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 16
Generalized Anxiety Disorder-7 (GAD-7)	Self-report of anxiety symptom severity; minimum score of 0 and maximum score of 21 with higher scores meaning worse outcome (more anxious)	Change in score relative to baseline calculated at week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 16.
Mystical Experience Questionnaire (MEQ)	Measure of perceptual experiences; multiple items rated on a 5 point scale with higher scores indicating more intense perceptual experience. Total scores are presented as an average (mean) of the 30 item scale, each of which are rated out of 5. Scale is ordered as follows (in reference to magnitude of various perceptual experiences during acute ketamine session): 0 - none; not at all; 1 - so slight cannot decide; 2 - slight; 3- moderate; 4 - strong (equivalent in degree to any other strong experience); 5- extreme (more than any other time in my life and stronger than 4).	Measured at week 1-8
Brief Pain Inventory (BPI)	Measure of pain. Sub-scale 3 specifically was reported for this outcome. Subjects were asked: "Please rate your pain by marking the box beside the number that best describes your pain at its worst in the last 24 hours"; maximum score of 10 and minimum of 0 with higher scores indicating worse outcome (more pain) and a score of 0 indicating best outcome (no pain).	Measured at baseline, week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, and 16
PTSD Checklist (PCL-5; PTSD Checklist 5)	Measure of PTSD symptoms; maximum score 80 and minimum score of 0 with higher scores indicating worse outcome (more PTSD symptoms)	Measured at week 1-9, 10, 12, and 16

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Eric T Dobson, MD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2022
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): March 20, 2023

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: December 30, 2021
• First Posted (Actual): January 14, 2022

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Mood Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Depressive Disorder; Opioid-Related Disorders; Depressive Disorder, Major; 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: Pro00115696

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No