Targeting Treatment-Resistant OUD With... — Clinical Trial Details

Targeting Treatment-Resistant OUD With Ketamine-Assisted Mindfulness Oriented Recovery Enhancement

This Phase II, randomised, double-blind trial (n=88) will evaluate the efficacy of Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy (KetaMORE) for individuals with opioid use disorder (OUD) receiving medication treatment. The primary aim is to determine whether participants receiving the KetaMORE intervention will show greater reductions in opioid use and craving compared to those receiving ketamine-assisted psychotherapy paired with a non-mindfulness support group. Participants will be randomly assigned to one of two conditions: the experimental group will receive ketamine-assisted psychotherapy alongside Mindfulness-Oriented Recovery Enhancement, while the control group will receive ketamine-assisted psychotherapy with a support group intervention that does not include mindfulness training. Both groups will undergo identical ketamine dosing and psychotherapy sessions, differing only in the adjunctive behavioural intervention. Key outcome measures will include the number of days of opioid use, time to first opioid use lapse, craving levels, and mood, assessed through ecological momentary assessments and standardised measures at various points throughout the study. The trial is set to begin in February 2026 and aims for completion by April 2028.

Detailed Description

The goal of this clinical trial is to examine the usefulness of Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy (KetaMORE) for individuals with opioid use disorder who are receiving medication treatment. The main question it aims to answer is whether individuals with opioid use disorder who receive Mindfulness-Oriented Recovery Enhancement in combination with Ketamine-Assisted Psychotherapy will demonstrate greater reductions in opioid use and craving than individuals who receive Ketamine-Assisted Psychotherapy with a non-mindfulness support group.

Participants will be randomly assigned to receive either Mindfulness-Oriented Recovery Enhancement combined with Ketamine-Assisted Psychotherapy or Ketamine-Assisted Psychotherapy combined with a support group control condition. Researchers will compare these groups on days of opioid use, time to first opioid use lapse, craving, and mood, assessed using ecological momentary assessments and standardized measures collected during treatment and follow-up.

Study Arms & Interventions

Ketamine-Assisted Psychotherapy Plus Mindfulness-Oriented Recovery Enhancement (KetaMORE)

experimental

Participants assigned to this arm will receive ketamine-assisted psychotherapy combined with Mindfulness-Oriented Recovery Enhancement (MORE). MORE is delivered as a structured, manualized behavioral intervention designed to reduce opioid use by targeting craving, negative affect, and maladaptive reward processing through mindfulness training, cognitive reappraisal, and savoring techniques.

Interventions

Ketamine

Participants

Ages

18 – ?

Sexes

All

BMI

Psychosis History

Inclusion Criteria

1. English-speaking .
2. DSM-5 criteria for Opioid Use Disorder (OUD).
3. Documented evidence (by urine toxicology) of current illicit drug use (upon screening) or by self-report on the Addiction Severity Index (ASI).
4. Men/Women \>/= 18
5. Current prescription of a buprenorphine-containing product.
6. Have a support person that would be able to escort the subject home on the evening of the ketamine dosing session. The use of ride services will not be permitted (e.g., Uber, Lift, taxi, etc.).
7. Agreement to adhere to Lifestyle Considerations

Exclusion Criteria

1\. A primary DSM-5 Axis I diagnosis of schizophrenia, schizoaffective disorder, dissociative identity disorder, or bipolar I/II disorder as determined by psychiatric evaluation.
2\. Has baseline hypertension (≥160 SBP or ≥100 DBP), after repeated measurements. Note: Participants with hypertension that has been controlled by medication down to \<160 Systolic blood pressure (SBP) and \<100 diastolic blood pressure (DBP) will be allowed participate.
3\. Has baseline abnormal resting heart rate (\>100 or \<60). 4. History of cardiovascular disease, including but not limited to clinically significant coronary artery disease, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, angina pectoris, coronary artery bypass graft or artificial heart valve, stroke, transient ischemic attack, or any clinically significant arrhythmia.
5\. Has QTcf \>450msec for men or women on EKG. Note: Participants may qualify for the study if QTc 450-480 msec on one EKG, but then \<=450 msec on repeat EKG. If QT-prolonging medications are started or increased in dose after enrollment and prior to ketamine administration, a repeat EKG must be done \>12-hours after this change in order to assure continued safe enrollment in the trial.
6\. Active suicidal intent or suicidal or non-suicidal self-injurious behaviors, as defined by a "yes" response to question 4 on C-SSRS within the past 6 months at screening or prior to dosing (Active Suicidal Ideation with Some Intent to Act, with or without Specific Plan).
7\. Suicidal behaviors within the last 6 month. 8. History of allergy or hypersensitivity reaction to ketamine. 9. History of ketamine use disorder. 10. History of intracranial bleeding or stroke. 11. Current intracranial mass. 12. Seizure within the last 6 months prior to screening visit. 13. Baseline oxygen saturation \<95%. 14. Current significant liver disease. 15. Meets the following laboratory parameters:
1. Any significant liver diseases or symptoms of liver disease regardless of liver enzyme levels.
2. Asymptomatic alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>=5x upper limit of normal (ULN).
3. Symptomatic ALT or AST \>= 2x ULN.
4. AST/ALT \>3 upper limit of normal (ULN)
5. Total bilirubin \> 1.5x ULN (Gilbert syndrome is allowed).
6. Alkaline phosphatase (ALP) \>2x ULN.
7. Renal insufficiency (i.e., estimated glomerular filtration rate (eGFR) \< 30 milliliter/minute (mL/min) /1.73 m\^2 (using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation), Creatinine Clearance (CrCl) \< 30 mL/min (using the Cockcroft-Gault Equation), or current dialysis)).
16\. Currently pregnant or breastfeeding. 17. Has uncontrolled insulin-dependent diabetes and has had a hospitalization for diabetes-related complication within 6 months of signing ICF.
18\. Diagnosed cognitive impairments, including dementia, mild cognitive impairment, traumatic brain injury, or developmental delays, that would prevent the participant from completing the study protocol, as identified by self-disclosure when asked in eligibility screening question.
19\. Individuals prescribed monoamine oxidase inhibitors.(see Appendix 1) 20. Individuals prescribed medications that are CYP2B6 inhibitors or inducers (see Appendix 1) 21. Patients taking \>2 mg of lorazepam-equivalents per day.

Company

Product

Legal

Targeting Treatment-Resistant OUD With Ketamine-Assisted Mindfulness Oriented Recovery Enhancement

Detailed Description

Study Arms & Interventions

Ketamine-Assisted Psychotherapy Plus Mindfulness-Oriented Recovery Enhancement (KetaMORE)

Interventions

Locations

Ketamine-Assisted Psychotherapy Plus Support Group

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators