Ketamine for OUD and Comorbid Depression (OUDCD)

NCT05051449 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: HP-00096377
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid Use Disorder; Depressive Disorder

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Patient Treatment Retention

  Three months

• Changes in Psychiatric Diagnosis of Depression

  One month

• Changes in Depressive Symptoms

  One month

Other Outcomes (11)

• Self-report of illicit substance use

  One month

• Subjective Opioid Withdrawal Scale (SOWS)

  One monrh

• Objective Opioid Withdrawal Scale (OOWS)

  One month

Study Arms (1)

Ketamine

EXPERIMENTAL

Drug: Ketamine Hydrochloride

Interventions

Ketamine Hydrochloride DRUG

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.

Ketamine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

University of Maryland Baltimore

Baltimore, Maryland, 21223, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders; Depressive Disorder

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Mood Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Annabelle Belcher, PhD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: September 21, 2021
• Study Start: April 4, 2022
• Primary Completion: November 17, 2023
• Study Completion: November 30, 2023
• Last Updated: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)