Ketamine for Opioid Use Disorder

University of Maryland Baltimore (UMB)

Status and phase: Begins enrollment in 2 months; Phase 2

Conditions: Opioid Use Disorder

Treatments: Drug: Treatment with Active Placebo; Drug: Treatment with Ketamine

Study type: Interventional

Funder types: Other

Identifiers

NCT06943859

HP-00114026

Details and patient eligibility

About

The goal of this clinical trial is to learn if ketamine works to reduce craving for opioids in adults entering methadone treatment for opioid use disorder. The main questions it aims to answer are:

• Does ketamine reduce craving for opioids in patients with opioid use disorder?
• Does ketamine reduce symptoms of opioid withdrawal such as depression, pain, and poor sleep quality?
• Do patients who take ketamine stay in methadone treatment longer, and/or have better treatment outcomes than those given the placebo?

Researchers will compare ketamine to an active placebo (a look-alike substance that contains a drug that does not do anything to help the condition it is supposed to treat but will mimic some of the side effects of ketamine) to see if ketamine works to reduce craving for opioids in adults entering methadone treatment for opioid use disorder.

Participants will:

• Be given ketamine or a placebo 4 times over a period of 2 weeks
• Visit the clinic weekly and monthly for checkups and tests for 90 days post-intake

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age 18 to 65 years old
2. Recent history (most recent 2 weeks prior to clinic intake) of routine use of illicit opioids, 5+ times/week
3. Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid use disorder
4. Acceptance into methadone treatment for opioid use disorder within the past 14 days at the time of screening.

Exclusion criteria

1. Routine use of prescribed medications for OUD (5+ days/week) for longer than the 14 days leading up to clinic intake. Source: Self-report, H&P

2. Recent prescribed or illicit benzodiazepine, ketamine, or PCP use that exceeds 5+ days/week for the last 3 months. Source: H&P

3. Pregnant and/or breastfeeding. Source: UDS, H&P

4. Stage 4 Hypertension, defined by a systolic blood pressure (SBP) > 180 mmHg or a diastolic blood pressure (DBP) > 120 mmHg. Source: H&P

5. Clinically significant abnormal findings for which study participation is deemed unsafe. Source: H&P

6. Severe mental illness or psychiatric disorder for which study participation is deemed unsafe (except for depression, PTSD, and substance use disorder). Source: H&P

7. **Severe hepatic impairment (baseline alkaline phosphatase or aspartate aminotransferase > 5 times the upper limit of normal. Source: Labs

   • NOTE: Due to time constraints in the study design, exclusion criterion #7 does not need to be met before the initial consent to participate. This criterion only needs to be established prior to the first esketamine/placebo session. This will allow us to enroll participants as soon as possible, giving more time and flexibility to complete the baseline/weekly assessments before the first esketamine/placebo session. Individuals that are initially enrolled and subsequently do not qualify due to severe hepatic impairment will be considered screen failures and withdrawn from the protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups, including a placebo group

Treatment with Ketamine

Experimental group

Description:

Individuals will receive four doses spaced 1-6 days apart of 0.75mg/kg of intramuscular ketamine (n=25) over a period of two weeks.

Treatment:

Drug: Treatment with Ketamine

Treatment with Placebo

Placebo Comparator group

Description:

Individuals will receive four doses spaced 1-6 days apart of an intramuscular active placebo (diphenhydramine, 50 mg) (n=25) over a period of two weeks.

Treatment:

Drug: Treatment with Active Placebo