MedPath

Ketamine for Opioid Use Disorder

Phase 2
Not yet recruiting
Conditions
Opioid Use Disorder
Interventions
Drug: Treatment with Ketamine
Drug: Treatment with Active Placebo
Registration Number
NCT06943859
Lead Sponsor
University of Maryland, Baltimore
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

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment with KetamineTreatment with KetamineIndividuals 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 with PlaceboTreatment with Active PlaceboIndividuals 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.
Primary Outcome Measures
NameTimeMethod
Tonic craving (FORCAST) total scoresCollected at baseline, weekly, 30-, 60-, and 90 days post-intake

Faceted Opioid Research Craving Assessment for Substance use Treatment (FORCAST): A 26-item assessment of tonic craving that the person reports having felt over the prior one or two weeks. Participants indicate how much they disagree or agree with each statement on a scale that ranges from 0-6, with 0 representing "strongly disagree", 3 representing "neither agree nor disagree", and 6 representing "strongly agree". Higher scores indicate higher levels of craving. The minimum score is 0, and the maximum scores for each of the subscales are as follows:

Preoccupation: 24 Negative Reinforcement: 30 Positive Reinforcement: 24 Motivation: 30 Lack of control: 24 Uneasiness: 24

Maximum total score for all subscales = 156

Secondary Outcome Measures
NameTimeMethod
Insomnia SymptomsISI collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake

Insomnia Severity Index (ISI): A five-item measure of current (past two weeks, or since last study visit) insomnia symptoms.

Severity of depression symptomsCompleted at baseline, weekly, 30-, 60-, and 90 days post-intake

Montgomery-Asberg Depression Rating Scale (MADRS): a 10-item questionnaire of depression severity. The total score ranges from 0-60, with scores of 0-6 considered normal (non-depressed), 7-19 indicative of mild depression, 20-34 indicative of moderate depression, and 35-60 indicative of severe depression. Item 10 on the instrument will be used to monitor any changes in suicidal ideation throughout the trial.

Cue-induced craving scoresCollected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake

Cue Reactivity Paradigm: our drug cue reactivity paradigm will be designed to elicit an acute craving state. We will present a series of opioid cue images continuously (total time \<5 min) via computer or tablet. Cues will be personalized based on each individual's drug use history as derived from baseline clinical assessments. For example, if a participant had no history of intravenous drug injection, we will not present opioid cue images containing injection paraphernalia like needles and instead will present images with opioid pills and/or powder. At the end of each one-minute session, participants will be asked to rate, on a scale of 1-10, "How much did you like the images you saw?", "How much do you want to use right now?", "How much do you want to avoid using right now?", "How much control do you feel you have over using right now" and "What is the maximum amount you would pay right now for a single dose of what you saw?"

Chronic pain ratingsCollected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake

Pain Brief Scale (PEG): A 3-item measure of past-week average pain intensity (P), interference with enjoyment of life (E), and interference with general activity (G).

Number of methadone doses received at 90 days post-intakeCollected through 90 days post-intake

Study team will have access to clinic records to assess the number of methadone doses patients have received at 90 days post-intake

Sleep quality ratingsPSQI collected at Baseline and 30-, 60-, and 90 days post-intake

Pittsburgh Sleep Quality Index (PSQI): A 19-item questionnaire assessing past-month sleep quality and disturbances. Seven component scores are generated: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for the 7 components yields one global score

Sleep quality ratings on a Visual Analogue Scale (VAS)SQS collected via daily optional EMAs through 90 days post-intake

Modified Single Item Sleep Quality Scale (SQS): A self-administered questionnaire that incorporates a VAS delivered electronically. SQS directs the patient to rate the overall quality of sleep over a 7-day period (modified for our study to rate the overall quality of sleep the past night) on a scale of 1-10 considering how many hours of sleep they had, how easily they fell asleep, how often they woke up during the night (excluding bathroom trips), how often they woke up earlier than intended

Scores on a holistic measure of recoveryCollected at baseline and at 30-, 60-, and 90 days post-intake

Substance Use Recovery Evaluator (SURE): A 21-item patient reported outcome measure of recovery from substance use disorder that has good face and content validity, acceptability and usability for people in recovery and is psychometrically valid.

Frequency of negative urine drug screens through 90 days post-intakecollected through 90 days post-intake

Study team will have access to clinic drug screenings through 90 days post-intake

Trial Locations

Locations (1)

University of Maryland Addiction Programs and Affiliated Clinics

🇺🇸

Baltimore, Maryland, United States

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