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Protocol Details

Brain Dopaminergic Signaling in Opioid use Disorders (OUD)

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

17-AA-0114

Sponsoring Institute

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 80

Referral Letter Required

No

Population Exclusion(s)

Pregnant Women and Fetuses;
Adults who are or may become unable to consent;
Children

Special Instructions

Currently Not Provided

Keywords

Raclopride;
[11C] NNC-112;
Functional Magnetic Resonance Imaging (fMRI);
Dopamine D1 Receptor;
D2 Receptors

Recruitment Keyword(s)

None

Condition(s)

Normal Physiology;
Opioid-Related Disorders

Investigational Drug(s)

[11C]raclopride
[11C]NNC-112

Investigational Device(s)

None

Intervention(s)

Drug: [11C]raclopride plus placebo
Drug: [11C]raclopride plus drug
Device: [11C]NNC-112

Supporting Site

National Institute on Alcohol Abuse and Alcoholism

Background:

The chemical messenger dopamine carries signals between brain cells. It may affect addiction. Heavy use of pain medicines called opioids may decrease the amount of dopamine available to the brain. Researchers want to study if decreased dopamine decreases self-control and increases impulsiveness.

Objective:

To learn more about how opiate use disorder affects dopamine in the brain.

Eligibility:

Adults 18-80 years old who are moderate or severe opiate users

Healthy volunteers the same age

Design:

Participants will first be screened under another protocol. They will:

-Have a physical exam

-Answer questions about their medical, psychiatric, and alcohol and drug use history

-Take an MRI screening questionnaire

-Give blood and urine samples

-Have their breath tested for alcohol

Participants will have up to 3 study visits.

They will have 2-3 positron emission tomography (PET) scans. A radioactive chemical will be injected for the scans. Participants will lie on a bed that slides in and out of the donut-shaped scanner. A cap or plastic mask may be placed on the head.

Vital signs will be taken before and after the PET scans.

Participants will get capsules of placebo or the study drug. They will rate how they feel before, during and after.

Participants will have their breath and urine tested each day.

Participants will have magnetic resonance imaging (MRI) scans. They will lie on a table that slides into a cylinder in a strong magnetic field. They may do tasks on a computer screen while inside the scanner.

Participants will have tests of memory, attention, and thinking.

Participants will wear an activity monitor for one week.

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Eligibility

INCLUSION CRITERIA:

Healthy Volunteer Participants

1. Males or females between 18 and 65 years of age.

2. Ability to provide written informed consent.

MAT- Opiate Use Disorder (OUD) Participants

1. Males or females between 18 and 65 years of age.

2. Ability to provide written informed consent.

3. DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam).

4. Active abuse of opiates (last use within one week of study as assessed by self-reports).

5. Minimum 3 year history of opiate abuse - self-report.

6. Must consume opiates at least 5 days per week as per self-report.

7. Currently not receiving medications for OUD (methadone, buprenorphine or naltrexone).

MAT+ OUD Participants

1. Males or females between 18 and 80 years of age.

2. Ability to provide written informed consent.

3. DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam).

4. Active or non-active abuse of opiates.

5. Minimum 3 year history of opiate abuse as per self-report.

6. Must have consumed at least 5 days per week (prior opiate use) as per self report.

7. Receiving opioid agonist therapy for OUD (e.g., methadone or buprenorphine) and must have taken for at least one week before imaging study

Naltrexone OUD Participants

1. Males or females between 18 and 65 years of age.

2. Ability to provide written informed consent.

3. DSM-5 diagnosis of a moderate or severe OUD (established through history and clinical exam).

4. Active or non-active abuse of opiates.

5. Minimum 3 year history of opiate abuse as per self-report.

6. Must have consumed at least 5 days per week (prior opiate use) as per self- report.

7. Receiving naltrexone treatment for their OUD and must have taken at least one week before imaging study.

For all groups of subjects regarding inclusion #1: OUD and HV subjects who are age 66-80 may be included in this study except they will not receive the methylphenidate and subsequent PET and MRI scans.

EXCLUSION CRITERIA:

-All Subjects

1. Current DSM-5 diagnosis of a psychiatric disorder (other than OUD or severe alcohol/substance use disorders in OUD participants and nicotine/caffeine use in all participants) that requires/required daily psychoactive medications (antidepressant, antipsychotics, stimulants, benzodiazepines or barbiturates) in the past two months and that could impact brain function at the time of the study as determined by history and clinical exam.

2. The following current chronically used (2 months) medications are exclusionary: stimulant or stimulant-like medications (amphetamine, methylphenidate, modafinil); opioid analgesics (for controls only); antianginal agents; antiarrhythmics; systemic corticosteroids; anticholinergics; anticoagulants; anticonvulsants; antidepressants; antihistamines (sedating); beta-blocker antihypertensives; antineoplastics; antiobesity; antipsychotics; anxiolytics (benzodiazepine or barbiturates); lithium; muscle relaxants; psychotropic drugs not otherwise specified (nos); sedatives/hypnotics, systemic steroids. Note that nicotine and/or caffeine is not exclusionary and that opiate drugs will not exclude participants with OUD. Subjects on stable antihypertensive medications (except for beta blockers) may be included provided they are clinically stable dose for at least a month [BP less than or equal to 140/90]. OUD subjects who have hypertension may still be included in this study except they will not receive the methylphenidate and subsequent PET and MRI scans.

3. Current continuous treatment (> 3 weeks) with methadone, buprenorphine or naltrexone for controls or MAT- OUD participants; or naltrexone for MAT+ OUD participants; or agonist treatment (methadone or buprenorphine) for OUD participants treated with Naltrexone.

4. Current major medical problems that can permanently impact brain function (e.g., CNS: including seizures, psychosis, stroke, severe depression, Alzheimer s, Parkinson s disease, Traumatic brain injury; Cardiovascular: including uncontrolled hypertension [BP > 140/90] and clinically significant arrhythmias except bradycardia; and HIV+) as determined by history. However, OUD subjects who have hypertension and/or certain EKG findings results may still be included in this study except they will not receive the methylphenidate and subsequent PET and/or MRI scans.

5. Clinically significant laboratory findings that could impact brain function or study procedures (e.g., active infections, arrhythmias, hepatic or renal failure) will be exclusionary.

6. Have had previous radiation exposure (from X-rays, PET scans, or other exposure) that, with the exposure from this study, would exceed NIH annual research limits as determined by medical history and physical exam.

7. Head trauma with loss of consciousness for more than 30 minutes as determined by medical history and physical exam.

8. Pregnant and/or currently breast-feeding. Females of childbearing potential (age 60 or less) will undergo a urine pregnancy test that must be negative to participate. Urine pregnancy tests will be repeated on subsequent days of study.

9. Presence of ferromagnetic objects in the body that are contraindicated for MRI (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 - self-report checklist. However, OUD subjects who are contraindicated for MRI participation, or the study team cannot access prior surgical records to confirm that a subject is cleared for MRI, may still participate in all aspects of the study except MRI. If it is discovered during the clinical brain MRI or after enrollment onto the study that the subject experiences anxiety or becomes claustrophobic, we will discontinue the MRI portion of the study and he/she can continue to participate in all other aspects of the study.

10. Personal or family history (parents or siblings) for cerebral aneurysm.

11. Past or present history of chest pain and trouble breathing with activity.

12. Glaucoma as assessed by medical history.

13. Cannot lie comfortably flat on their backs for up to 2 hours in the PET and MRI scanners self-report.

14. Weight > 400 pounds, which is the maximum weight the PET scanner can hold.

15. Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).

Additional exclusion criteria for MAT+ / MAT- / Naltrexone OUD participants:

16. Participation in a court ordered residential treatment program.

Additional exclusion criteria for MAT- OUD participants only:

17. Currently seeking treatment for OUD, for the MAT- group.

Note that subjects will not be excluded from enrollment onto this study if their urine test is positive for drugs on initial screening. The following guidelines will be followed for positive drug screens on study procedure days:

-If a Healthy Volunteer subject s urine drug screen test is positive on days involving imaging (MRI and/or PET) and NP testing, the procedures will be postponed and rescheduled. We will allow for up to 3 rescheduled study days resulting from positive urine drug screens. If urine drug screen is positive for THC-COOH, a saliva drug screen will be performed and subject may proceed with study day testing procedures if saliva results for THC are negative. If the urine/saliva drug test is positive on the third rescheduled visit, the participant will be withdrawn from the study.

-If an OUD subject s urine drug screen test is positive for drugs (other than opiates), the procedures will not be postponed. If urine drug screen is positive for THC-COOH, a saliva drug screen will be performed to verify if THC is present. Positive results for drugs other than opiates will be considered at the time of data analysis as a co-variate.

Also, note that at any time during participation in this study if any subject expresses that he/she wants to get treatment for their OUD, we will immediately refer him/her to a treatment program. The subject will be withdrawn from the study at that time. No medications will be stopped or held for participation in this protocol.


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

Gene-Jack Wang, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)



Gene-Jack Wang, M.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
BG 10 RM B2L124
10 CENTER DR
BETHESDA MD 20814
(301) 496-5012
gene-jack.wang@nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT03190954

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