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Ketamine for OUD and Comorbid Depression (OUDCD)

Primary Purpose

Opioid Use Disorder, Depressive Disorder

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Ketamine Hydrochloride

About this trial

This is an interventional treatment trial for Opioid Use Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria

From NHS prescreen (no contact, Study Day 0): Between the ages of 18 to 65 years old
From NHS prescreen (no contact, Study Day 0): Daily use of illicit opioids
From NHS prescreen (no contact, Study Day 0): Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid or heroin use disorder
From NHS prescreen (no contact, Study Day 0): Acceptance into methadone maintenance care for treatment of opioid or heroin use disorder
From screening for study eligibility (Study Contact Day 1): A total of 10 or more points on the PHQ-9
From screening for study eligibility (Study Contact Day 1): Have had no prior sustained experience/dependence on ketamine or PCP (i.e., must answer "no" to all four questions on the ketamine/PCP screen)

Exclusion Criteria

From NHS prescreen (no contact, Study Day 0): Patients transferring from another program of opioid agonist treatment
From NHS prescreen (no contact, Study Day 0): Electrocardiogram (ECG) findings of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction
From NHS prescreen (no contact, Study Day 0): Self-report of recent prescribed or illicit benzodiazepine use ("Xannies", or "bars")
From NHS prescreen (no contact, Study Day 0): Urine screen positive for pregnancy
From NHS prescreen (no contact, Study Day 0): Stage 2 hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg or a diastolic blood pressure (DBP) > 90 mmHg
From NHS prescreen (no contact, Study Day 0): Clinically significant abnormal laboratory values, physical exam findings or self-reported medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g., cardiovascular disease), as determined by the evaluating intake physician
From NHS prescreen (no contact, Study Day 0): Any clinically significant abnormal findings from intake health and physical examination
From NHS prescreen (no contact, Study Day 0): Any indication of serious mental illness or psychiatric disorder from the attending's evaluation notes
From Liver Function Screen (Study Contact Day 2): Baseline alkaline phosphatase > 2.5 times the upper limit of normal
From Liver Function Screen (Study Contact Day 2): Baseline aspartate aminotransferase > 3 times the upper limit of normal
From Psychiatric Evaluation (Study Contact Day 2) Current or previous recreational use of ketamine or PCP
From Psychiatric Evaluation (Study Contact Day 2): Subjects who meet DSM-5 criteria for current bipolar disorder
From Psychiatric Evaluation (Study Contact Day 2): Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder
Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders

Sites / Locations

University of Maryland BaltimoreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketamine

Arm Description

Outcomes

Primary Outcome Measures

Feasibility: Study Recruitment

Feasibility will be assessed via participant recruitment: 50% of eligible patients approached will consent to participation in the pilot.

Feasibility: Study Retention

75% of participants will be retained throughout the duration of ketamine infusion procedures

Patient Acceptability: Acceptability of the Intervention Measure (AIM)

Acceptance will be assessed via scores on the Acceptability of the Intervention Measure (AIM): Distribution summarized with mean and 95% C.I. Scale values range from 1 to 5 with higher mean values representing greater agreement and/or acceptability.

Patient Acceptability: Engagement

Engagement will be assessed via dosing records of observed ketamine administration: distribution of percentage of completed infusions per patient.

Secondary Outcome Measures

Patient Treatment Retention

One-month (30-day) methadone treatment retention as a binomial (yes/no) variable outcome.

Changes in Psychiatric Diagnosis of Depression

Assessment of changes in depression (MADRS score) will be made at baseline and on the final study day based on a Minimal Clinically Important Difference (MCID) defined change of 1.9 points

Changes in Depressive Symptoms

Assessment of changes in symptoms of depression, measured with the Patient Health Questionnaire (PHQ-9) will be made at baseline and on the final study day.

Full Information

NCT ID

NCT05051449

First Posted

September 10, 2021

Last Updated

August 8, 2023

Sponsor

University of Maryland, Baltimore

1. Study Identification

Unique Protocol Identification Number

NCT05051449

Brief Title

Ketamine for OUD and Comorbid Depression (OUDCD)

Official Title

Increasing Retention in Methadone Maintenance Treatment: Feasibility and Preliminary Efficacy of Ketamine for the Treatment of Patients With OUD and Comorbid Depression (OUDCD)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 4, 2022 (Actual)

Primary Completion Date

November 1, 2023 (Anticipated)

Study Completion Date

November 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Methadone is a first-line, evidence-based treatment for opioid use disorder (OUD). Unfortunately, retention and adherence in methadone treatment is a major challenge. OUD patients frequently present with co-morbid depression (OUDCD), a risk factor for poor OUD treatment outcomes, overdose, and suicide. The last two decades have seen an exciting and transformational development in the treatment of depression - ketamine. As a safe, rapid-acting anti-depressant deliverable within the context of methadone maintenance treatment, ketamine could feasibly change the landscape of treatment for OUD patients with comorbid depression. This proposal seeks to evaluate implementation outcomes (feasibility and patient acceptance) as well as preliminary efficacy of ketamine on methadone treatment outcomes for OUD patients (n=6) with comorbid depression and depressive symptoms presenting for methadone treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Opioid Use Disorder, Depressive Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ketamine

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Ketamine Hydrochloride

Intervention Description

Ketamine will be administered by a nurse in a 2-week treatment phase, during which participants will receive six IV infusions of 0.5 mg/kg (over 40-50 minutes) ketamine three times per week. Infusion days for patients will be on Mondays, Wednesdays, and Fridays, +/- 1 day. Ketamine infusions will take place at the UMB General Clinical Research Center (GCRC). The GCRC nurse will deliver ketamine within a private exam room. The infusions will last 40-50 min, and the participant will be observed by the GCRC clinical staff for 2 hours post-infusion. Vital signs will be monitored throughout the treatment; specifically, blood pressure, pulse ox and heart rate will be checked prior to treatment, q20 minutes during infusion, and q30-60 minutes after infusion for up to three hours.

Primary Outcome Measure Information:

Title

Feasibility: Study Recruitment

Description

Feasibility will be assessed via participant recruitment: 50% of eligible patients approached will consent to participation in the pilot.

Time Frame

One year

Title

Feasibility: Study Retention

Description

75% of participants will be retained throughout the duration of ketamine infusion procedures

Time Frame

One year

Title

Patient Acceptability: Acceptability of the Intervention Measure (AIM)

Description

Time Frame

One month

Title

Patient Acceptability: Engagement

Description

Engagement will be assessed via dosing records of observed ketamine administration: distribution of percentage of completed infusions per patient.

Time Frame

One month

Secondary Outcome Measure Information:

Title

Patient Treatment Retention

Description

One-month (30-day) methadone treatment retention as a binomial (yes/no) variable outcome.

Time Frame

Three months

Title

Changes in Psychiatric Diagnosis of Depression

Description

Assessment of changes in depression (MADRS score) will be made at baseline and on the final study day based on a Minimal Clinically Important Difference (MCID) defined change of 1.9 points

Time Frame

One month

Title

Changes in Depressive Symptoms

Description

Assessment of changes in symptoms of depression, measured with the Patient Health Questionnaire (PHQ-9) will be made at baseline and on the final study day.

Time Frame

One month

Other Pre-specified Outcome Measures:

Title

Self-report of illicit substance use

Description

Assessment of changes in number of days of substance use from baseline to the last study contact. Drug use is assessed via self-report of past-two-week use of four common substances: opioids (including heroin, fentanyl, and nonprescribed opioids), cocaine, benzodiazepines, and alcohol; "other" is a fifth category. Total days used (out of a possible 14) is recorded.

Time Frame

One month

Title

Subjective Opioid Withdrawal Scale (SOWS)

Description

Assessment of changes in scores on the SOWS from baseline to the last study contact day. SOWS is a 16-item patient self-report instrument to assess common subjective symptoms of craving and withdrawal.

Time Frame

One monrh

Title

Objective Opioid Withdrawal Scale (OOWS)

Description

Assessment of changes in scores on the OOWS from baseline to the last study contact day. The OOWS is a 13-item clinical assessment of observable physiological signs of withdrawal.

Time Frame

One month

Title

Craving Assessment

Description

Assessment of changes in scores on the Craving Assessment from baseline to the last study contact day. This assessment is an adapted one-item visual-analog scale of self-report of craving for drugs.

Time Frame

One month

Title

Pittsburgh Sleep Quality Index (PSQI)

Description

Assessment of changes in scores on the PSQI from baseline to the last study contact day. The PSQI is a self-rated 19-item questionnaire that assesses sleep quality and disturbances over a one-month time interval. Seven component scores are generated: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for the 7 components yields one global score. Assessment of changes will be based on the global score.

Time Frame

One month

Title

The Short Inventory of Problems-Revised (SIP-R)

Description

Assessment of changes in scores on the SIP-R from baseline to the last study contact day. The SIP-R is a 15-item self-report assessment of the adverse consequences of substance use.

Time Frame

One month

Title

Generalized Anxiety Disorder 7-item scale (GAD-7)

Description

Assessment of changes in scores on the GAD-7 from baseline to the last study contact day. The GAD-7 is a 7-item screen designed to identify individuals with probable anxiety. Each item is scored with a score between 0 and 3 (Not at all sure= 0; Several days= 1; Over half the days= 2; Nearly every day= 3), yielding a total between 0 and 21.

Time Frame

One month

Title

Acceptability of the Intervention (AIM)

Description

Assessment of changes in scores on the AIM from baseline to the last study contact day. An established implementation instrument used widely in clinical research, the AIM is a 4-item Likert-type measure of acceptability of an intervention.

Time Frame

One month

Title

Clinician Administered Dissociative Symptom Scale (CADSS-6)

Description

Assessment of changes in scores on the CADSS-6 across ketamine infusion days. The CADSS-6 is a 6-item clinician-administered assessment of treatment-emergent dissociation, an adverse event associated with I.V. ketamine; administered 5-10 minutes following cessation of the ketamine infusion on all infusion days

Time Frame

Two weeks

Title

Drug Effects Questionnaire-5 (DEQ-5)

Description

Assessment of changes in scores on the CADSS-6 across ketamine infusion days. The DEQ is a five-point self-report visual analogue scale-based assessment of two key aspects of an individual's acute, subjective response to the experience of drug consumption: (i) the strength of substance effects and (ii) desirability of substance effects; administered immediately following CADSS-6 administration.

Time Frame

Two weeks

Title

Modified Aldrete

Description

This assessment determines safe discharge from the hospital following each day of ketamine infusion, and will be administered just prior to release. This 5-point clinical assessment is used as a post-operative tool to determine safe discharge following anesthesia. Scores of 0 to 2 are assigned to each of five domains, which include Activity, Respiration, Circulation, Consciousness and Oxygen Saturation.

Time Frame

Two weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria From NHS prescreen (no contact, Study Day 0): Between the ages of 18 to 65 years old From NHS prescreen (no contact, Study Day 0): Daily use of illicit opioids From NHS prescreen (no contact, Study Day 0): Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid or heroin use disorder From NHS prescreen (no contact, Study Day 0): Acceptance into methadone maintenance care for treatment of opioid or heroin use disorder From screening for study eligibility (Study Contact Day 1): A total of 10 or more points on the PHQ-9 From screening for study eligibility (Study Contact Day 1): Have had no prior sustained experience/dependence on ketamine or PCP (i.e., must answer "no" to all four questions on the ketamine/PCP screen) Exclusion Criteria From NHS prescreen (no contact, Study Day 0): Patients transferring from another program of opioid agonist treatment From NHS prescreen (no contact, Study Day 0): Electrocardiogram (ECG) findings of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction From NHS prescreen (no contact, Study Day 0): Self-report of recent prescribed or illicit benzodiazepine use ("Xannies", or "bars") From NHS prescreen (no contact, Study Day 0): Urine screen positive for pregnancy From NHS prescreen (no contact, Study Day 0): Stage 2 hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg or a diastolic blood pressure (DBP) > 90 mmHg From NHS prescreen (no contact, Study Day 0): Clinically significant abnormal laboratory values, physical exam findings or self-reported medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g., cardiovascular disease), as determined by the evaluating intake physician From NHS prescreen (no contact, Study Day 0): Any clinically significant abnormal findings from intake health and physical examination From NHS prescreen (no contact, Study Day 0): Any indication of serious mental illness or psychiatric disorder from the attending's evaluation notes From Liver Function Screen (Study Contact Day 2): Baseline alkaline phosphatase > 2.5 times the upper limit of normal From Liver Function Screen (Study Contact Day 2): Baseline aspartate aminotransferase > 3 times the upper limit of normal From Psychiatric Evaluation (Study Contact Day 2) Current or previous recreational use of ketamine or PCP From Psychiatric Evaluation (Study Contact Day 2): Subjects who meet DSM-5 criteria for current bipolar disorder From Psychiatric Evaluation (Study Contact Day 2): Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Annabelle Belcher, PhD

Phone

443-462-3400

Abelcher@som.umaryland.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Sarah Kattakuzhy, MD

Phone

443-691-4638

SKattakuzhy@ihv.umaryland.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Annabelle Belcher, PhD

Organizational Affiliation

University of Maryland, Baltimore

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Maryland Baltimore

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21223

Country

United States

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Ketamine for OUD and Comorbid Depression (OUDCD)

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