Ketamine for Opioid Use Disorder

Phase 2RecruitingNCT06943859

University of Maryland, Baltimore50 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Opioid Use Disorder

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Tonic craving (FORCAST) total scores

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

Time frame: Collected at 7 days pre- and post-ketamine, 30-, and 90-days post-final ketamine session

Secondary Outcomes

Severity of depression symptoms

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.

Time frame: Completed at 7 days pre- and post-ketamine, 30-, and 90-days post final ketamine session

Cue-induced craving scores

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?"

Time frame: 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

Graded Chronic Pain Scale (GCPS): a six-item instrument that evaluates chronic pain severity (intensity and impact on life activities).

Time frame: 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

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

Time frame: Collected through 90 days post final ketamine session

Sleep quality ratings

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

Time frame: PSQI collected at 7 days pre- and post-ketamine, 30-, and 90 days post-final ketamine session

Insomnia Symptoms

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

Time frame: 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)

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

Time frame: 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

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.

Time frame: 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

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

Time frame: collected through 90 days post final ketamine session