Ketamine for OUD and Comorbid Depression (OUDCD)

Study Overview
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Brief Summary
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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.

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

Conditions
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Depressive Disorder, Opioid Use Disorder

Intervention / Treatment
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* Drug: Ketamine Hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine<br> | Drug: Ketamine Hydrochloride<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Treatment Retention | One-month (30-day) methadone treatment retention as a binomial (yes/no) variable outcome. | Three months | 
| 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 | One month | 
| 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. | One month |