Imaging Biomarker for Addiction Treatment Outcome

Opioid-Related Disorders Clinical Trial

Official title: Imaging Biomarker for Addiction Treatment Outcome

Status Terminated

Clinical Trial Summary

Background:

Many people suffer from drug addiction. But currently, treatments are not very effective. One group of patients in this study are enrolled in addiction treatment through physician health programs (PHPs). About 70% of these patients are able to stop using drugs for extended periods of time. By studying this specific group of patients, researchers want to understand the difference between those who may or may not respond to treatment. They want to study the brain while people do thinking and feeling tasks and when they relax. They will study brain chemicals, a stress hormone, and certain genes. The results may help them understand the brain basis for addiction and recovery.

Objectives:

To use brain imaging to find differences between people with and without drug addiction. To see if these differences help predict addiction.

Eligibility:

Healthy, right-handed adults ages 21-65, enrolled in a physician health program or those with no history of addiction and with at least 16 years of education

Design:

Participants enrolled in a PHP will be screened under this study and participants with no history of addiction will be screened under another study.

At the study visit, participants will:

Have a routine check-up, including tests for pregnancy, drugs, and alcohol.

Give 11 blood samples.

Rate their cravings.

Test their frustration with stressful situations by responding to questions on a screen.

Practice the magnetic resonance imaging (MRI) tasks:

Shock task. Two electrodes placed on a foot will deliver brief, low-strength electrical shocks that get gradually stronger, but not painful. Participants will see drug or neutral images. They will rate their discomfort.

Thinking tasks. Participants will answer questions about pictures, numbers, and money. They will press buttons in response to things they see.

Do the MRI tasks in 2 sessions (morning and afternoon) in the scanner. Participants will lie in an MRI machine which will take pictures of the brain while doing these tasks.

Some participants will repeat the visit twice over a year at set intervals.

Meals will be provided, and visits will include meal breaks and smoking breaks for those who smoke.

Clinical Trial Description

Objective:

Despite recent advances in addiction neuroscience, achieving a breakthrough in predicting addiction treatment outcome has been difficult and long-term abstinence success unacceptably low. The aim of this study is to create a biomarker using various neuroimaging metrics that can predict treatment outcome in opioid, alcohol and dual opioid and alcohol use disorder patients.

Study Population:

Total study enrollment will include up to 650 participants. The main study population will include up to five hundred (500) participants to reach three hundred fifty (350) completers (50 per group) based on their addiction status (1) healthy, non-drug using control participants (CON) (2) Early-in-treatment, healthy prescription opioid use disorder participants currently enrolled in physician health program (PHP) within 3 months of starting treatment (POUD-E), (3) Long-term-in-treatment, healthy prescription opioid use disorder participants currently enrolled in or affiliated with a PHP more than 2 months (POUD-L), (4) Early-in-treatment, healthy alcohol use disorder participants currently enrolled in PHP within 3 months of starting treatment (AUD-E), (5) Long-term-in-treatment, healthy alcohol use disorder participants currently enrolled in or affiliated with a PHP more than 2 months (AUD-L), (6) Early-in-treatment, healthy dual prescription opioid and alcohol and use disorder participants currently enrolled in PHP within 3 months of starting treatment (POAUD-E), (7) Long-term-in-treatment, healthy dual prescription opioid and alcohol use disorder participants currently enrolled in or affiliated with a PHP more than 2 months (POAUD-L). The Addiction Phenotype Characterization arm will include up to 150 completers.

Design:

The main study includes two studies that will run simultaneously:

Cross-sectional study that will include participants who have been in treatment for more than 2 months and are either enrolled at a PHP if within the required monitoring period of 5 years or still affiliated with their PHP after successfully completing their 5-year monitoring period. Three target groups, in addition to the control group, will be included in this study [POUD-L, AUD-L, and POAUD-L]. Each participant will complete a screening evaluation session (approximately 3-4 hours) and a second session for study consent review (approximately 1-2 hours) at home or at the PHP through secure communication. These sessions will include the screening consent process, administration of a structured psychiatric interview and a semi-structured assessment, instructions for the completion of detailed self-administered questionnaires to characterize clinical phenotype and physical condition, and consent review for the study. Participants subsequently cleared for and enrolled in the cross-sectional study will be invited to come to NIDA IRP for one imaging visit that will take approximately 8-10 hours.

The aim of the cross-sectional study is to identify imaging based brain differences between control group and drug using groups and to examine correlations between brain imaging markers at different stages of recovery and (1) severity of drug use (duration and quantity), (2) duration of abstinence, and (3) number of relapses in drug using groups.

The primary outcome measure for the cross-sectional study will be differences in functional connectivity and BOLD signal activation in executive and impulsive neurobehavioral decision systems at various stages of sobriety in relation to controls.

Longitudinal study that will include participants who are enrolled at a PHP within about three months of starting treatment. Three groups, in addition to the control group, will be included in this study [POUD-E, AUD-E, and POAUD-E]. Each participant will complete the screening sessions as described in the cross-sectional study. Eligible participants will undergo three imaging visits at NIDA; 1) 1st (baseline) visit within about 2 months of eligibility determination, (2) 2nd (mid-year) visit within 4-8 months of baseline visit and (3) 3rd (one-year) visit within 10-14 months of baseline visit. Each imaging visit will take approximately 8-10 hours.

The aim of the longitudinal study is to measure brain imaging changes over time in abstinent and relapsing addicts and to identify brain imaging markers that differentiate between abstinent and relapsing participants at 6 months and at 1 year. The rationale behind the mid-year visit is that most relapses take place early (within the first 6 months) during treatment and, by one year, some of those who relapsed earlier achieve abstinence. We chose one year follow up in order to compare brain imaging changes between abstinent and relapsing participants after relatively long sobriety and to add clinical value to our prediction model. By including both of these visits, we will obtain three scans on both abstinent without early relapse and abstinent with early relapse in order to uncover salient brain differences between those who relapse early and those who maintain abstinence.

The primary outcome measure for the longitudinal study will be differences in baseline and changes over time in functional connectivity circuits and BOLD signal activation in executive and impulsive neurobehavioral decision systems between abstinent and relapsing addicts that can predict treatment response at 6 and 12 months. Most importantly, we will use imaging, behavioral and genetic measures at the onset of treatment in a machine-learning framework in an attempt to predict subsequent treatment success in this cohort of participants.

Secondary outcome measures for both studies will be phenotypic (performance on behavioral tasks, self-reported measures of cravings, impulsivity and personality traits), genotypic and imaging (structural, functional and spectroscopy) differences between different addiction groups.

The Addiction Phenotype Characterization arm will include participants who are ineligible for the main study due to imaging-related exclusions or other medical exclusions (e.g. medications, other SUD disorders). These participants will complete the characterization measures (structured psychiatric interview, a semi-structured drug use history assessment, and several self-administered questionnaires to characterize clinical phenotype and physical condition).

The aim of the Addiction Phenotype Characterization arm is to characterize addiction phenotype and physical condition in health professionals.

The primary outcome measures for the Addiction Phenotype Characterization arm are the characterization measures. ;

Related Conditions & MeSH terms

• Alcohol-Related Disorders
• Opioid-Related Disorders

• NCT number: NCT03427424
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Terminated
• Start date: July 10, 2019
• Completion date: April 29, 2024