Imaging Biomarker for Addiction Treatment Outcome

ID: NCT03427424
Status: Not yet recruiting
Phase: N/A
Start Date: March 01, 2018
First Submitted: February 08, 2018
Last Updated: February 23, 2018
Results: N/A
Sponsors & Collaborators: National Institute on Drug Abuse (NIDA)
Location: United States
Conditions: Opioid-Related Disorders, Alcohol-Related Disorders
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Study Description

Brief 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 25 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.

Detailed Description

Objective:

Despite recent advance 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 and alcohol use disorder patients.

Study Population:

The study population will include three hundred fifty (350) participants (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 2 month of starting treatment (POUD-E), (3) Long-term-in-treatment, healthy prescription opioid use disorder participants currently enrolled in PHP more than 2 months and less than 5 years (POUD-L), (4) Early-in-treatment, healthy alcohol use disorder participants currently enrolled in PHP within 2 month of starting treatment (AUD-E), (5) Long-term-in-treatment, healthy alcohol use disorder participants currently enrolled in PHP more than 2 months and less than 5 years (AUD-L), (6) Early-in-treatment, healthy dual prescription opioid and alcohol and use disorder participants currently enrolled in PHP within 2 month of starting treatment (POAUD-E), (7) Long-term-in-treatment, healthy dual prescription opioid and alcohol use disorder participants currently enrolled in PHP more than 2 months and less than 5 years (POAUD-L).

Design: Two studies will run simultaneously:

1. Cross-sectional study that will include all participants enrolled at a PHP over the past 5 years and have been in treatment for more than 2 months. 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) at the PHP through secure communication. The screening visit will include the consenting process and the administration of questionnaires to characterize clinical phenotype, and physical condition. Participants enrolled in the cross-sectional study will be invited to come to NIDA IRP for one imaging visit that will take approximately 6-8 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.

2. Longitudinal study that will include all participants enrolled at PHP within two months of starting treatment. Three groups, in addition to the control group, will be included in this study [POUD-E, AUDE, and POAUD-E]. Each participant will complete the screening evaluation session as described in the cross-sectional study and three imaging visits at NIDA; 1) baseline visit within 2 months from enrolling in the study, (2) mid-year visit within 4-8 months from baseline visit and (3) one-year visit within 10-14 months from baseline visit. Each imaging visit will take approximately 6-8 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 and by including this visit, we will preclude a contaminated sample of both abstinent without early relapse and abstinent with early relapse which could confound our results. The primary outcome measure for the longitudinal study will be differences in baseline and changes over time in functional connectivity circuits, 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.

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 and spectroscopy) differences between different addiction groups.
Condition or disease Intervention/treatment Phase

Alcohol-Related Disorders

Opioid-Related Disorders

N/A

Tracking Information

First Submitted DateFebruary 08, 2018
Last Update Posted DateFebruary 23, 2018
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateDecember 31, 2022
Anticipated Primary Completion DateDecember 31, 2022
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • For 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 control [Time Frame: 1 study visit]

  • For the longitudinal study will be differences in baseline and changes over time in functional connectivity circuits, BOLD signal activation in executive and impulsive neurobehavioral decision systems between abstinent and relapsing addicts that... [Time Frame: 6 & 12 mo f/u visits]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Phenotypic (performance on behavioral tasks, self-reported measures of cravings, impulsivity and personality traits), genotypic and imaging (structural and spectroscopy) differences between different addiction groups. [Time Frame: At each visit]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleImaging Biomarker for Addiction Treatment Outcome
Official TitleImaging Biomarker for Addiction Treatment Outcome
Brief 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 25 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.

Detailed Description

Objective:

Despite recent advance 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 and alcohol use disorder patients.

Study Population:

The study population will include three hundred fifty (350) participants (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 2 month of starting treatment (POUD-E), (3) Long-term-in-treatment, healthy prescription opioid use disorder participants currently enrolled in PHP more than 2 months and less than 5 years (POUD-L), (4) Early-in-treatment, healthy alcohol use disorder participants currently enrolled in PHP within 2 month of starting treatment (AUD-E), (5) Long-term-in-treatment, healthy alcohol use disorder participants currently enrolled in PHP more than 2 months and less than 5 years (AUD-L), (6) Early-in-treatment, healthy dual prescription opioid and alcohol and use disorder participants currently enrolled in PHP within 2 month of starting treatment (POAUD-E), (7) Long-term-in-treatment, healthy dual prescription opioid and alcohol use disorder participants currently enrolled in PHP more than 2 months and less than 5 years (POAUD-L).

Design: Two studies will run simultaneously:

1. Cross-sectional study that will include all participants enrolled at a PHP over the past 5 years and have been in treatment for more than 2 months. 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) at the PHP through secure communication. The screening visit will include the consenting process and the administration of questionnaires to characterize clinical phenotype, and physical condition. Participants enrolled in the cross-sectional study will be invited to come to NIDA IRP for one imaging visit that will take approximately 6-8 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.

2. Longitudinal study that will include all participants enrolled at PHP within two months of starting treatment. Three groups, in addition to the control group, will be included in this study [POUD-E, AUDE, and POAUD-E]. Each participant will complete the screening evaluation session as described in the cross-sectional study and three imaging visits at NIDA; 1) baseline visit within 2 months from enrolling in the study, (2) mid-year visit within 4-8 months from baseline visit and (3) one-year visit within 10-14 months from baseline visit. Each imaging visit will take approximately 6-8 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 and by including this visit, we will preclude a contaminated sample of both abstinent without early relapse and abstinent with early relapse which could confound our results. The primary outcome measure for the longitudinal study will be differences in baseline and changes over time in functional connectivity circuits, 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.

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 and spectroscopy) differences between different addiction groups.

Study TypeObservational
Study PhaseN/A
Estimated Enrollment
500
Allocation
Not Available
Interventional Model
Not Available
Masking
Not Available
Primary Purpose
Not Available
Conditions
Alcohol-Related Disorders
Opioid-Related Disorders
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodNon-Probability Sample
Study PopulationThe study population will include three hundred fifty (350) participants (50 per group) based on their addiction status. This study uses seven parallel groups - healthy subjects, subjects with alcohol use disorder in early in-treatment physician health programs (PHP), subjects with opioid use disorder in early in-treatment PHP, subjects with alcohol use disorder in longterm in-treatment PHP, subjects with opioid use disorder in longterm in-treatment PHP, subjects with alcohol and opioid use disorders in early in-treatment PHP and subjects with alcohol and opioid use disorders in long in-treatment PHP.
Intervention
Not Available
Study Groups/Cohorts
1-Healthy Participants
healthy, non-drug using control participants (CON)

6-Early-in-treatment with opioid and alcohol use disorder
(6) Early-in-treatment, healthy dual prescription opioid and alcohol use disorder participants currently enrolled in PHPs within 2 month of starting treatment (POAUD-E),

4-Early-in-treatment with alcohol use disorder
(4) Early-in-treatment, healthy alcohol use disorder participants currently enrolled in PHPs within about 2 month of starting treatment (AUD-E),

5-Long-term-in-treatment with alcohol use disorder
(5) Long-term-in-treatment, healthy alcohol use disorder participants currently enrolled in PHPs more than 2 months and less than 5 years (AUD-L),

3-Long-term-in-treatment with opioid use disorder
(3) Long-term-in-treatment, healthy prescription opioid use disorder participants currently enrolled in PHPs more than 2 months and less than 5 years (POUD-L),

7-Long-term-in-treatment with opioid and alcohol use disorder
(7) Long-term-in-treatment, healthy dual prescription opioid and alcohol use disorder participants currently enrolled in PHPs more than 2 months and less than 5 years (POAUD-L).

2-Early-in-treatment with opioid use disorder
Early-in-treatment, healthy prescription opioid use disorder participants currently enrolled in physician health programs (PHP) within about 2 month of starting treatment (POUD-E),

Study Arms
Not Available
Arm Intervention/Treatment

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment500
Completion DateDecember 31, 2022
Eligibility Criteria: - INCLUSION CRITERIA:
All participants: healthy, non-drug using control participants (CON), Early-in-treatment, healthy prescription opioid use disorder participants (POUD-E), Long-term-in-treatment, healthy prescription opioid use disorder participants (POUD-L), Early-in-treatment, healthy alcohol use disorder participants (AUD-E), Long-term-in-treatment, healthy alcohol use disorder participants (AUD-L), Early-in-treatment, healthy dual prescription opioid and alcohol and use disorder participants (POAUD-E), Long-term-intreatment, healthy dual prescription opioid and alcohol use disorder participants (POAUD-L).
1. Both males and females between 25-65 years of age will be enrolled in the study.
2. Able and willing to provide written informed consent.
3. Participants must be right-handed.
4. Participants must be in good health..
Healthy control participants (CON) in addition to all participant s inclusion criteria
5. Participants will be best matched in age, gender, race, and years of education.
6. Free of lifetime DSM-5 substance use disorders Assessment tool(s): The MINI-plus and clinical substance abuse/dependence assessment.
Early-in-treatment, prescription opioid use disorder (POUD-E) participants- in addition to all participant s inclusion criteria
7. Recently (within about 2 months) enrolled in a physician health program (PHP) or equivalent at time of enrollment in the study
8. Meet a minimum of 6/11 DSM-5 criteria for severe opioid use disorder for at least 2 years prior to enrollment and in full remission for at least 2 months at time of imaging. Assessment tool: DSM 5 Opioid Use Disorder Checklist.
Early-in-treatment, alcohol use disorder (AUD-E) participants- in addition to all participant s inclusion criteria
9. Recently (within about 2 months) enrolled in a physician health program (PHP) or equivalent at time of enrollment in the study
10. Meet a minimum of 6/11 DSM-5 criteria for severe alcohol use disorder for at least 2 years prior to enrollment and in full remission for at least 2 months at time of imaging. Assessment tool: DSM 5 Alcohol Use Disorder Checklist.
Early-in-treatment, dual prescription opioid and alcohol use disorder (POAUD-E) participants- in addition to all participant s inclusion criteria
11. Recently (within about 2 months) enrolled in a physician health program (PHP) or equivalent at time of enrollment in the study
12. Meet a minimum of 6/11 DSM-5 criteria for either severe opioid or severe alcohol use disorders and a minimum of 4/11 DSM-5 for either moderate opioid or moderate alcohol use disorder at least 2 years for each substance prior to enrollment and in full remission for at least 2 months at time of imaging. Assessment tool: DSM 5 Opioid Use Disorder and Alcohol Use Disorder Checklists.
Long-term-in-treatment, prescription opioid use disorder (POUD-L) participants- in addition to all participant s inclusion criteria
13. Enrolled in a physician health program (PHP) or equivalent for more than 2 months and less than 5 years at time of enrollment in the study
14. Meet a minimum of 6/11 DSM-5 criteria for severe opioid use disorder for at least 2 years prior to starting treatment and in full remission for at least 2 months at time of imaging. Assessment tool: DSM 5 Opioid Use Disorder Checklist.
Long-term-in-treatment, alcohol use disorder (AUD-L) participants- in addition to all participant s inclusion criteria
15. Enrolled in a physician health program (PHP) or equivalent for more than 2 months and less than 5 years at time of enrollment in the study
16. Meet a minimum of 6/11 DSM-5 criteria for severe alcohol use disorder for at least 2 years prior to starting treatment. Assessment tool: DSM 5 Alcohol Use Disorder Checklist and in full remission for at least 2 months at time of imaging.
Long-term-in-treatment, dual prescription opioid and alcohol use disorder (POAUD-E) participants
17. Enrolled in a physician health program (PHP) or equivalent for more than 2 months and less than 5 years at time of enrollment in the study
18. Meet a minimum of 6/11 DSM-5 criteria for either severe opioid or severe alcohol use disorders and a minimum of 4/11 DSM-5 for either moderate opioid or moderate alcohol use disorder at least 2 years for each substance prior to enrollment and in full remission for at least 2 months at time of imaging. Assessment tool: DSM 5 Opioid Use Disorder and Alcohol Use Disorder Checklists.
EXCLUSION CRITERIA:
1. All participants; healthy non-drug using control participants (CON), Early-in-treatment, healthy prescription opioid use disorder participants (POUD-E), Long-term-intreatment, healthy prescription opioid use disorder participants (POUD-L), Early-intreatment, healthy alcohol use disorder participants (AUD-E), Long-term-in-treatment, healthy alcohol use disorder participants (AUD-L), Early-in-treatment, healthy dual prescription opioid and alcohol and use disorder participants (POAUD-E), Long-term-in-treatment, healthy dual prescription opioid and alcohol use disorder participants (POAUD-L).
2. Females must not be pregnant. Assessment: negative urine pregnancy test prior to each study session. Please note that breast feeding per se is not an exclusion since there is no exposure to radiation and no administration of any pharmacological compounds will be done in the study.
3. Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (e.g. pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces. Assessment tool: MRI safety screening form.
4. Noise-induced hearing loss or tinnitus.
Assessment tool: MRI safety screening form.
5. Head trauma with loss of consciousness or significant sequelae for more than 30 minutes. Assessment tool: medical history and physical exam.
6. Current or past DSM-5 diagnosis of any psychiatric disorder other than nicotine use disorder (please note that nicotine smoking is not exclusionary), opioid use disorder in opioid use disorder participants and alcohol use disorder in alcohol use disorder participants and both opioid and alcohol use disorders in the dual opioid and alcohol use disorder group that required hospitalization other than detoxification (any length), or chronic medication management for more than three months, (except for stable doses of antidepressants) and that could impact brain function at the time of the study based on study MAI s discretion. Assessment tool: history and clinical exam.
7. Currently (at time of imaging sessions) using any medications that are known to alter BOLD signal such as stimulant or stimulant-like medications (amphetamine, methylphenidate, modafinil); anorexics (sibuteramine); antianginal agents; antiarrhythmics; antiasthma agents that are systemic corticosteroids; anticholinergics; anticonvulsants; antineoplastics; antiobesity; antipsychotics; hormones (exceptions: thyroid hormone replacement, oral contraceptives, and estrogen replacement therapy); insulin; lithium; herbal products with known psychotropic effects (e.g. Gingko biloba, or St johns wart) and other medications based on study MAI s discretion. Assessment tool: medical history
8. Currently (at time of imaging sessions) taking methadone opioid replacement therapy or buprenorphine. Please note that participants taking disulfiram, acamprosate, naltrexone, or long acting naltrexone treatment will be allowed to participate in the study Assessment tool: medical history.
9. Medical conditions that can impact brain function such as seizure disorder, diabetes mellitus, renal insufficiency (e.g. Creatinine > 2.5), uncontrolled hypertension (BP>160/100 on screening), uncontrolled or severe coronary artery disease, clinically significant heart disease, HIV, syphilis, or autoimmune disorders. Assessment tool: medical history.
10. Clinically significant laboratory results (e.g. random glucose > 200 mg/dL, LFT > 3-fold upper limit of normal, or Hemoglobin < 10 gm/dL) or other clinically significant lab abnormalities based on study MAI s discretion. Assessment tool: screening laboratory examination.
GenderAll
Age25 Years to 65 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT03427424
Other Study ID Numbers
999918053
18-DA-N053
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
National Institute on Drug Abuse (NIDA)
Collaborators
Not Available
Investigators
Principal Investigator
Elliot Stein, Ph.D.
National Institute on Drug Abuse (NIDA)