Ketamine for Opioid Use Disorder

University of Maryland Baltimore (UMB)

Status and phase: Enrolling; Phase 2

Conditions: Opioid Use Disorder

Treatments: Drug: Treatment with Very Low Dose Ketamine; 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 enrolled in 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 the low dose ketamine stay in methadone treatment longer, and/or have better treatment outcomes than those given the very low dose?

Researchers will compare two low doses of ketamine to see if ketamine works to reduce craving for opioids in adults enrolled in methadone treatment for opioid use disorder.

Participants will:

• Be given a low dose or a very low dose of ketamine 4 times over a period of 2 weeks
• Visit with the study team one week prior to the first ketamine session, one week following the last ketamine session, at 30 days following the final ketamine session, and 90 days following the final ketamine session for checkups and tests

Enrollment: 50 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Age 18 to 65 years old
2. Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid use disorder
3. Acceptance into methadone treatment for opioid use disorder at the time of screening.
4. Adherence to lifestyle requirements for participation.
5. Self-reported craving greater than or equal to 20 out of 100 for opioids at any point in the past week at time of screening
6. Positive UDS for opioids or self-reported illicit opioid use in the past three months at time of screening

Exclusion Criteria

1. Pregnant and/or breastfeeding.

2. **Stage 2 Hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg or a diastolic blood pressure (DBP) > 90 mmHg.

3. Abnormal oxygen saturation or abnormal heart rate (i.e. O2 saturation <95%, or HR <60 or >100bpm

4. Clinically significant abnormal findings for which study participation is deemed unsafe.

5. Severe mental illness or psychiatric disorder for which study participation is deemed unsafe (except for depression, PTSD, and substance use disorder).

6. **ALT/AST > 3 x Upper Limit of Normal (ULN), ALP 2 x ULN, or total bilirubin > 1.5 x ULN.

7. History of hypersensitivity to ketamine.

8. Suicidal ideation with a plan or intent or suicidal behaviors as reflected in Columbia-Suicide Severity Rating Scale (C-SSRS).

9. Recent homicidal ideation or violent behaviors.

10. Concomitant daily use of medications with significant CYP2B6 and CYP3A4 inhibition or induction effects that can interfere with metabolism of ketamine.

11. Advanced cardiopulmonary disorders, including stroke, cardiac arrest, and myocardial infarction in the past year

12. History of aneurysmal vascular disease or dissection (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation.

13. **Clinically significant EKG abnormalities.

14. Current significant use (>3 days/week) of barbiturates, sedative hypnotics, benzodiazepines, ketamine, or PCP (prescribed or illicit).

    • NOTE: Due to time constraints in the study design, these exclusion criteria do not need to be met before the initial consent to participate. This criterion only needs to be established prior to the first ketamine session. This will allow us to enroll participants as soon as possible, giving more time and flexibility to complete the baseline assessments before the first ketamine 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. Because repeated ketamine administration is associated with hepatobiliary dysfunction (most often a cholestatic pattern) we will also obtain a follow up LFT within 30 days of the final ketamine session.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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50 participants in 2 patient groups

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 Very Low Dose Ketamine

Active Comparator group

Description:

Individuals will receive four doses spaced 1-6 days apart of an intramuscular ketamine (0.1mg/kg) (n=25) over a period of two weeks.

Treatment:

Drug: Treatment with Very Low Dose Ketamine