Clinical trial NCT06943859: Ketamine for Opioid Use Disorder
Official title: Ketamine for the Treatment of Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Opioid Use Disorder
Keywords: opioid use disorder
ketamine
craving
treatment adherence
methadone
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2025-04-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Tonic craving (FORCAST) total scores
timeFrame: Collected at baseline, weekly, 30-, 60-, and 90 days post-intake
Secondary outcomes:
measure: Severity of depression symptoms
timeFrame: Completed at baseline, weekly, 30-, 60-, and 90 days post-intake
measure: Cue-induced craving scores
timeFrame: Collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake
measure: Chronic pain ratings
timeFrame: Collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake
measure: Number of methadone doses received at 90 days post-intake
timeFrame: Collected through 90 days post-intake
measure: Sleep quality ratings
timeFrame: PSQI collected at Baseline and 30-, 60-, and 90 days post-intake
measure: Insomnia Symptoms
timeFrame: ISI collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake
measure: Sleep quality ratings on a Visual Analogue Scale (VAS)
timeFrame: SQS collected via daily optional EMAs through 90 days post-intake
measure: Scores on a holistic measure of recovery
timeFrame: Collected at baseline and at 30-, 60-, and 90 days post-intake
measure: Frequency of negative urine drug screens through 90 days post-intake
timeFrame: collected through 90 days post-intake
Other outcomes:
measure: Decision making test performance (risk and ambiguity tolerance)
timeFrame: collected weekly through 90 days post-intake via optional EMAs
measure: Methadone dose (mg) at 90 days post-intake
timeFrame: collected through 90 days post-intake
measure: OUD treatment outcomes at 6-, 9-, and 12 months post intake
timeFrame: collected through 6-, 9-, and 12 months post intake
Locations:
city: Baltimore
country: United States
facility: University of Maryland Addiction Programs and Affiliated Clinics
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Peter Manza, PhD
role: PRINCIPAL_INVESTIGATOR
References: