Ketamine for the Treatment of Opioid Use Disorder
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Tonic craving (FORCAST) total scores
Study Overview
Brief Summary
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age 18 to 65 years old
- •Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid use disorder
- •Acceptance into methadone treatment for opioid use disorder at the time of screening.
- •Adherence to lifestyle requirements for participation.
- •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
- •Positive UDS for opioids or self-reported illicit opioid use in the past three months at time of screening
Exclusion Criteria
- •Pregnant and/or breastfeeding.
- •**Stage 2 Hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg or a diastolic blood pressure (DBP) > 90 mmHg.
- •Abnormal oxygen saturation or abnormal heart rate (i.e. O2 saturation <95%, or HR <60 or >100bpm
- •Clinically significant abnormal findings for which study participation is deemed unsafe.
- •Severe mental illness or psychiatric disorder for which study participation is deemed unsafe (except for depression, PTSD, and substance use disorder).
- •**ALT/AST > 3 x Upper Limit of Normal (ULN), ALP 2 x ULN, or total bilirubin > 1.5 x ULN.
- •History of hypersensitivity to ketamine.
- •Suicidal ideation with a plan or intent or suicidal behaviors as reflected in Columbia-Suicide Severity Rating Scale (C-SSRS).
- •Recent homicidal ideation or violent behaviors.
- •Concomitant daily use of medications with significant CYP2B6 and CYP3A4 inhibition or induction effects that can interfere with metabolism of ketamine.
- •Advanced cardiopulmonary disorders, including stroke, cardiac arrest, and myocardial infarction in the past year
- •History of aneurysmal vascular disease or dissection (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation.
- •**Clinically significant EKG abnormalities.
- •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.
Arms & Interventions
Treatment with Ketamine
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.
Intervention: Treatment with Ketamine (Drug)
Treatment with Very Low Dose Ketamine
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.
Intervention: Treatment with Very Low Dose Ketamine (Drug)
Outcomes
Primary Outcomes
Tonic craving (FORCAST) total scores
Time Frame: Collected 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
Tonic craving (FORCAST) total scores
Time Frame: Collected at 7 days pre- and post-ketamine, 30-, and 90-days post-final ketamine session
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 Outcomes
- Insomnia Symptoms(ISI collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake)
- Severity of depression symptoms(Completed at baseline, weekly, 30-, 60-, and 90 days post-intake)
- Cue-induced craving scores(Collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake)
- Chronic pain ratings(Collected at Baseline, weekly following intake, 30-, 60-, and 90 days post-intake)
- Number of methadone doses received at 90 days post-intake(Collected through 90 days post-intake)
- Sleep quality ratings(PSQI collected at Baseline and 30-, 60-, and 90 days post-intake)
- Sleep quality ratings on a Visual Analogue Scale (VAS)(SQS collected via daily optional EMAs through 90 days post-intake)
- Scores on a holistic measure of recovery(Collected at baseline and at 30-, 60-, and 90 days post-intake)
- Frequency of negative urine drug screens through 90 days post-intake(collected through 90 days post-intake)
- Severity of depression symptoms(Completed at 7 days pre- and post-ketamine, 30-, and 90-days post final ketamine session)
- Cue-induced craving scores(Collected at 7 days pre- and post-ketamine, 7 days pre- and post ketamine, ketamine administration days, 30-, and 90-days post-final ketamine session)
- Chronic pain ratings(Collected at 7 days pre- and post-ketamine, ketamine administration days, 30-, and 90-days post-final ketamine session)
- Number of methadone doses received at 90 days post final ketamine session(Collected through 90 days post final ketamine session)
- Sleep quality ratings(PSQI collected at 7 days pre- and post-ketamine, 30-, and 90 days post-final ketamine session)
- Insomnia Symptoms(Collected at 7 days pre- and post-ketamine, ketamine administration days, 30-, 90-days post-final ketamine session)
- Sleep quality ratings on a Visual Analogue Scale (VAS)(SQS collected via daily optional EMAs through 7 days post final ketamine session, then every other day until 90 days post final ketamine session)
- Scores on a holistic measure of recovery(Collected at 7 days pre- and post-ketamine, 30-, and 90 days post-final ketamine session)
- Frequency of negative urine drug screens through 90 days post final ketamine session(collected through 90 days post final ketamine session)
Investigators
Peter Manza
Assistant Professor
University of Maryland, Baltimore