Low-dose ketamine to reduce opioid craving in people starting methadone

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

Adults who recently began methadone for moderate-to-severe opioid use disorder will be randomized to receive either a low dose or a very low dose of ketamine four times over two weeks. Participants will attend weekly and monthly clinic visits and safety checks for 90 days after intake to measure opioid craving, withdrawal-related symptoms (including depression, pain, and sleep), and treatment retention. Safety monitoring includes vital signs and screening for psychiatric or cardiovascular contraindications. Outcomes in the two dosing groups will be compared to determine whether the higher low dose yields better craving reduction and retention without unacceptable side effects.

Why it matters

Who can join: the full rules

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.

Where it's running

• University of Maryland Addiction Programs and Affiliated Clinics
  Baltimore, Maryland, United States Recruiting

Study contacts

• Principal investigator: Peter Manza, PhD — University of Maryland, Baltimore
• Study coordinator: Peter Manza, PhD
• Email: peter.manza@som.umaryland.edu
• Phone: 410-706-2814

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.