Ignite Creation Date:
2024-05-06 @ 10:12 AM
Last Modification Date:
2024-10-26 @ 12:26 PM
Study NCT ID:
NCT03190954
Status:
RECRUITING
Last Update Posted:
2024-04-05
First Post:
2017-06-16
Brief Title:
Brain Dopaminergic Signaling in Opioid Use Disorders
Sponsor:
National Institute on Alcohol Abuse and Alcoholism NIAAA
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Brain Dopaminergic Signaling in Opioid Use Disorders OUD
Status:
RECRUITING
Status Verified Date:
2024-10-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
Detailed Description:
Objectives Primary objective is to assess whether the balance between dopamine D1 D1R and D2 receptors D2R signaling in striatum is disrupted in participants with an opioid use disorder OUD who are on opioid agonist medication MAT methadone or buprenorphine relative to OUD participants treated with the opioid antagonist medication naltrexone and OUD participants in recovery and not being treated with medications MAT- Secondary objectives are to assess how striatal D1R to D2R availability assessed with PET influences 1 striatal dopamine DA release 2 the function of brain reward and self-control networks assessed with task fMRI activation and with resting functional connectivity RFC and 3 behavior locomotor activity and neuropsychological tests 4 to assess if DA increases as induced by oral methylphenidate MP improve the function of brain reward and control networks in OUD and 5 to assess if there is recovery after protracted treatment comparing treated and non-treated by repeating fMRI at 6 month follow-up
Study population We will complete studies in 180 n180 subjects N60 healthy control adults and N120 OUD participants 60 MAT 30 naltrexone-treated and 30 MAT- aged 18-80 malefemale will be included
Design Single-blind Participants will undergo three scans with positron emission tomography PET one with 11CNNC-112 to assess baseline D1R another with 11Craclopride after placebo to assess baseline D2R and a third one with 11Craclopride after MP administration 60mg oral to assess striatal DA release assessed as the difference in specific binding of 11Craclopride between baseline and MP In addition participants will undergo two imaging sessions with MRI to assess functional reactivity to drug-cues and to a measure of self-control delayed discounting task to assess RFC and to obtain structural brain measures including diffusion tensor imaging DTI One of the sessions will be done under baseline conditions no drug administered and the other after MP about one hour after the 11Craclopride MP scan is completed Neuropsychological tests NP and accelerometers will be used to assess cognitive performance and locomotor activity respectively
Outcome Measures Main outcome 1 Differences in D1R to D2R striatal ratio between participants with an OUD and controls and between MAT naltrexone and MAT- groups Secondary outcomes Correlations between striatal D1R to D2R and 1 striatal DA release 2 fMRI activation in reward and controls networks assessed with cue-reactivity and delay discounting tasks and with RFC and 3 NP performance and locomotor activity 4 Differences in fMRI activation and RFC after MP when compared with baseline measures
Study population We will complete studies in 180 n180 subjects N60 healthy control adults and N120 OUD participants 60 MAT 30 naltrexone-treated and 30 MAT- aged 18-80 malefemale will be included
Design Single-blind Participants will undergo three scans with positron emission tomography PET one with 11CNNC-112 to assess baseline D1R another with 11Craclopride after placebo to assess baseline D2R and a third one with 11Craclopride after MP administration 60mg oral to assess striatal DA release assessed as the difference in specific binding of 11Craclopride between baseline and MP In addition participants will undergo two imaging sessions with MRI to assess functional reactivity to drug-cues and to a measure of self-control delayed discounting task to assess RFC and to obtain structural brain measures including diffusion tensor imaging DTI One of the sessions will be done under baseline conditions no drug administered and the other after MP about one hour after the 11Craclopride MP scan is completed Neuropsychological tests NP and accelerometers will be used to assess cognitive performance and locomotor activity respectively
Outcome Measures Main outcome 1 Differences in D1R to D2R striatal ratio between participants with an OUD and controls and between MAT naltrexone and MAT- groups Secondary outcomes Correlations between striatal D1R to D2R and 1 striatal DA release 2 fMRI activation in reward and controls networks assessed with cue-reactivity and delay discounting tasks and with RFC and 3 NP performance and locomotor activity 4 Differences in fMRI activation and RFC after MP when compared with baseline measures
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 17-AA-0114 | None | None | None |