Evaluation of Ketamine for Relapse Prevention in Opioid Use Disorder: A Clinical Trial Assessing Efficacy and Biomarker Identification

The primary objective of this study is to address two pivotal aspects in the treatment of **Opioid Use Disorder**. Firstly, the study aims to identify biomarkers that can predict the vulnerability of individuals to relapse into opioid use during periods of abstinence. Secondly, it seeks to evaluate the efficacy of **ketamine** as an adjunctive treatment to existing pharmacotherapies for opioid addiction. This includes investigating whether ketamine can extend periods of abstinence, diminish cravings, and reduce the likelihood of relapse following abstinence. These objectives are clinically relevant as they aim to enhance the understanding and management of relapse prevention in opioid addiction, potentially leading to improved treatment outcomes.

Secondary objectives include identifying biological markers that can: (i) predict increased craving for opioids, and (ii) predict the efficacy of ketamine in preventing relapse in opioid addicts. These objectives are crucial for tailoring personalized treatment strategies and improving the therapeutic efficacy of interventions for opioid addiction.

The clinical trial focuses on individuals diagnosed with **Opioid Use Disorder**, encompassing both male and female participants. The study population includes adults aged 18 to 65 years, who are currently engaged in maintenance care for the treatment of opioid or heroin use disorder. Participants are required to have a score of 10 or more on the PHQ-9, indicating the presence of depression symptoms, and must be retained in opioid use treatment. The trial does not specifically target a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or other habits are not specified in the available data.

The clinical trial is designed to evaluate the **efficacy** of **ketamine** in preventing relapse in patients with **Opioid Use Disorder** (OUD). This study is a **randomized, double-blind, controlled** trial, conducted over a period of approximately three years, with an estimated end date of December 31, 2025. The trial aims to assess the potential of ketamine as a complementary treatment to existing pharmacotherapies, focusing on prolonging abstinence, reducing cravings, and reversing comorbid negative affective behaviors. The primary endpoints include the maintenance of abstinence and reduction in cravings, while secondary endpoints involve the identification of predictive biomarkers and the association between ketamine-induced changes in brain activity and treatment outcomes.

Participants will be involved in the study for a maximum treatment period of six weeks, during which they will receive ketamine via **intravenous infusion**. The inclusion criteria require participants to be aged between 18 to 65 years, accepted into maintenance care for opioid or heroin use disorder, have a score of 10 or more on the PHQ-9 indicating depression symptoms, and be retained in opioid use treatment. The study begins with a screening visit to confirm eligibility, followed by baseline assessments. Subsequent study visits will occur at regular intervals to monitor the participants' response to treatment and collect data on primary and secondary endpoints. The end-of-study visit will involve final assessments and data collection.

Participants may be withdrawn from the study if they experience adverse effects, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The trial is categorized as a Phase IV study, exploring the efficacy of ketamine treatment in a non-low intervention setting. The study's main objective is to identify biomarkers predicting relapse vulnerability and evaluate ketamine's role in enhancing treatment outcomes for OUD patients.

The clinical trial involves the use of **ketamine** as the experimental medication. **Ketamine** is administered in the form of a **solution for injection**. The active substance, **ketamine**, is of chemical origin. The administration route for this trial is **intravenous infusion**. The dosing regimen specifies a maximum daily dose of 0.5 mg/kg and a maximum total dose of 3 mg/kg over the course of the treatment. The treatment period is limited to a maximum of 6 weeks. The trial aims to evaluate the efficacy of **ketamine** in preventing relapse in patients with opioid-use disorders by potentially prolonging abstinence periods, reducing cravings, and decreasing the likelihood of relapse.

In addition to the experimental treatment, participants may receive standard-of-care therapies for opioid addiction as part of their treatment regimen. These therapies are not specified in the trial data but typically include pharmacotherapies such as methadone, buprenorphine, or naltrexone. The trial does not include a placebo or comparator treatment group. Compliance with the dosing schedule and administration is monitored throughout the study to ensure adherence to the protocol and to assess the treatment's efficacy accurately.

The efficacy of ketamine in the prevention of relapse in patients with **Opioid-Use Disorders (OUD)** will be assessed through a series of primary and secondary endpoints. The primary endpoints include the reversal of comorbid negative affective behaviors, prolongation or maintenance of abstinence in OUD patients, and reduction in cravings. These endpoints will be measured using validated scales and patient-reported outcomes to ensure accuracy and reliability.

Secondary endpoints focus on the identification of predictive biomarkers, such as emotion regulation ability, stress response biomarkers, and changes in neural activity. Additionally, the association between ketamine-induced changes in brain activity and treatment outcomes will be evaluated. These assessments will involve laboratory tests and neuroimaging techniques to provide comprehensive data on the efficacy of ketamine as a complementary treatment for opioid addiction.