Ketamine for OUD and Comorbid Depression (OUDCD)

• ClinicalTrials.gov Identifier: NCT05051449
• Recruitment Status: Recruiting
• First Posted: September 21, 2021
• Last Update Posted: January 10, 2023
• Sponsor: University of Maryland, Baltimore
• Information provided by (Responsible Party): Annabelle Belcher, University of Maryland, Baltimore

Tracking Information

• First Submitted Date: September 10, 2021
• First Posted Date: September 21, 2021
• Last Update Posted Date: January 10, 2023
• Actual Study Start Date: April 4, 2022
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 22, 2021)

• Feasibility: Study Recruitment [ Time Frame: One year ]
  Feasibility will be assessed via participant recruitment: 50% of eligible patients approached will consent to participation in the pilot.
• Feasibility: Study Retention [ Time Frame: One year ]
  75% of participants will be retained throughout the duration of ketamine infusion procedures
• Patient Acceptability: Acceptability of the Intervention Measure (AIM) [ Time Frame: One month ]
  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 [ Time Frame: One month ]
  Engagement will be assessed via dosing records of observed ketamine administration: distribution of percentage of completed infusions per patient.

Original Primary Outcome Measures (submitted: September 10, 2021)

• Feasibility: Study Recruitment [ Time Frame: One year ]
  Feasibility will be assessed via participant recruitment: 50% of eligible patients approached will consent to participation in the pilot.
• Feasibility: Study Retention [ Time Frame: One year ]
  75% of participants will be retained throughout the duration of ketamine infusion procedures
• Patient Acceptability: AIM [ Time Frame: One month ]
  Acceptance will be assessed via scores on the Acceptability of the Intervention Measure: distribution summarized with mean and 95% C.I.
• Patient Acceptability: Engagement [ Time Frame: One month ]
  Engagement will be assessed via dosing records of observed ketamine administration: distribution of percentage of completed infusions per patient.

Current Secondary Outcome Measures (submitted: October 7, 2022)

• Patient Treatment Retention [ Time Frame: Three months ]
  One-month (30-day) methadone treatment retention as a binomial (yes/no) variable outcome.
• Changes in Psychiatric Diagnosis of Depression [ Time Frame: One month ]
  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 [ Time Frame: One month ]
  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.

Original Secondary Outcome Measures (submitted: September 10, 2021)

• Patient Treatment Retention [ Time Frame: Three months ]
  One-month (30-day) methadone treatment retention as a binomial (yes/no) variable outcome.
• Changes in Psychiatric Diagnosis of Depression [ Time Frame: One month ]
  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

Current Other Pre-specified Outcome Measures (submitted: October 7, 2022)

• Self-report of illicit substance use [ Time Frame: One month ]
  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.
• Subjective Opioid Withdrawal Scale (SOWS) [ Time Frame: One monrh ]
  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.
• Objective Opioid Withdrawal Scale (OOWS) [ Time Frame: One month ]
  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.
• Craving Assessment [ Time Frame: One month ]
  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.
• Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: One month ]
  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.
• The Short Inventory of Problems-Revised (SIP-R) [ Time Frame: One month ]
  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.
• Generalized Anxiety Disorder 7-item scale (GAD-7) [ Time Frame: One month ]
  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.
• Acceptability of the Intervention (AIM) [ Time Frame: One month ]
  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.
• Clinician Administered Dissociative Symptom Scale (CADSS-6) [ Time Frame: Two weeks ]
  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
• Drug Effects Questionnaire-5 (DEQ-5) [ Time Frame: Two weeks ]
  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.
• Modified Aldrete [ Time Frame: Two weeks ]
  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.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Opioid Use Disorder
• Depressive Disorder

Intervention

Drug: Ketamine Hydrochloride

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.

Study Arms

Experimental: Ketamine

Intervention: Drug: Ketamine Hydrochloride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 10, 2021): 6
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Annabelle Belcher, PhD; 443-462-3400; Abelcher@som.umaryland.edu

Contact: Sarah Kattakuzhy, MD; 443-691-4638; SKattakuzhy@ihv.umaryland.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05051449
• Other Study ID Numbers: HP-00096377
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Annabelle Belcher, University of Maryland, Baltimore
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Maryland, Baltimore
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Annabelle Belcher, PhD; University of Maryland, Baltimore

• PRS Account: University of Maryland, Baltimore
• Verification Date: January 2023