Multi-System Analysis of Opioid Receptor Binding
- Conditions
- Opioid Use DisorderHealthy
- Interventions
- Registration Number
- NCT05528848
- Lead Sponsor
- University of Pennsylvania
- Brief Summary
This study will enroll up to 60 adults (including 30 females and 30 males) in three cohorts of up to 20 subjects each. In all three groups, \[11C\]carfentanil whole-body PET imaging will be used to examine the central nervous system (CNS) and broader systemic opioid binding in an initial scan session. In the two groups not receiving standard of care medication assisted treatment (MAT) for opioid use disorder (OUD) the effects on \[11C\]carfentanil binding potential of the blockade of opioid binding by the non-selective opioid antagonist naloxone administered parenterally in a second scan session will also be examined. If two scans are completed they can be done on the same day or on different days.
- Detailed Description
This study will enroll up to 60 adults (including 30 females and 30 males) in three cohorts \[Opioid Use Disorder (OUD) + medication-assisted treatment (MAT), OUD - MAT, or Healthy Controls\] up to 20 subjects each. In all three groups, \[11C\]carfentanil whole-body PET imaging will be used to examine the central nervous system (CNS) and broader systemic opioid binding in an initial scan session. In the two groups not receiving standard of care medication assisted treatment (MAT) for opioid used disorder (OUD), the effects on \[11C\]carfentanil binding potential of the blockade of opioid binding by the non-selective opioid antagonist naloxone administered parenterally in a second scan session will also be examined. If two scans are completed they can be done on the same day or on different days.
Findings from this study will demonstrate the distribution of opioid effects in brain and other organs in healthy controls and individuals with opioid use disorder (OUD), including those treated with the opioid agonists buprenorphine or methadone. Thus, this project will inform clinically relevant questions related to OUD.
In all three groups we would also like to collect a blood sample to be used for future testing, including genome-wide micro-array testing that may be used for genome-wide association studies (GWAS). Approximately 13 mL of blood will be drawn and stored for future testing. This blood draw will occur once but could be done at any visit. Participants who have already completed the imaging study may be recontacted and reconsented to complete this blood draw, if they agree.
PET/CT imaging will be used to evaluate the distribution of opioid effects in the brain and other organs using the investigational radiotracer \[11C\]carfentanil. Each subject will have an initial \[11C\]carfentanil positron emission tomography/computed tomography (PET/CT) scan. Subjects not receiving MAT for OUD may undergo a second scan that includes pretreatment with parenteral naloxone. For subjects participating in the HC cohort who agree to undergo a 3rd PET scan, the scan may be done up to 2 years after their original PET scans. However, depending on the length of time since initial enrollment subjects may be undergo repeat screening or baseline assessments (including screening labs or psychological assessments) at the discretion of an investigator prior to undergoing the 3rd scan to confirm that no eligibility criteria have changed in the period since initial scanning. We will do an interval baseline/screening assessment in which we take a history and complete a physical exam informed by the prior history and physical, and update them. We will repeat labs and query concomitant meds (also as warranted by the history). We will not repeat cognitive testing. We will repeat the work-up with anyone whose prior assessment occurred longer than a 1 year from re-contact.
Analyses will compare the binding potential (BPND) in the brain and other body parts across the three cohorts (OUD+/MAT+, OUD+/MAT-, HC). In the two groups not receiving MAT (OUD+/MAT- and HC), binding potential and distribution will be compared between subjects by contrasting the \[11C\]carfentanil-only scan with the \[11C\]carfentanil scan preceded by naloxone treatment. A structural MRI scan of the brain and spinal cord will be conducted before the PET scan to permit co-registration and the identification of specific brain regions on PET scan.
During each PET scan, participants will undergo approximately 90 minutes of dynamic scanning of the brain and body in a whole-body PET/CT scanner. PET/CT imaging sessions will include an injection of ≤ 15 mCi (approximate range for most studies is anticipated to be 5-15 mCi) of \[11C\]carfentanil. In the non-MAT groups, a dose of naloxone will be injected intravenously approximately 10-15 minutes before the \[11C\]carfentanil injection. Data will be collected to evaluate the uptake of \[11C\]carfentanil in the brain and other organs with and without naloxone blockade. Venous blood samples will be taken during the scan session to measure radioactive counts and/or bio-metabolites. For participants in Cohort 1 who are on MAT an additional approximately 5 mL of blood will be drawn prior to injection of \[11C\]carfentanil to measure MAT levels.
HC subjects who undergo a 3rd scan, on the day of the scan, will be given an oral dose of loperamide hydrochloride (IMODIUM®) 45-75 minutes prior to the \[11C\]carfentanil injection and the start of the scan.
Subjects are required to have had a brain MRI performed within 1 year prior to study enrollment (subjects participating in the HC cohort and undergoing a 3rd scan will not have to repeat the MRI if they previously completed an MRI), or if the subject has not had a brain MRI deemed acceptable for use for this study, they will be asked to undergo a research brain MRI after they have consented for this study.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Opioid Use Disorder and Medication Assisted Treatment (OUD+/MAT-) Naloxone Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the first study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the second study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the second scan session and there will be a break between the two scan sessions of approximately 3 hours. Opioid Use Disorder Only (OUD+/MAT-) Naloxone Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the first study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the second study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the second scan session and there will be a break between the two scan sessions of approximately 3 hours. Healthy Controls (OUD-) Naloxone Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the 1st study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the 2nd study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the 2nd scan and there will be a break between the two scans of approximately 3 hours. For the optional 3rd study scan 4 mg capsule or 30 mL solution standard adult dose of loperamide hydrochloride will be given orally 45-75 minutes prior to the\[11C\]carfentanil injection. Healthy Controls (OUD-) Loperamide Hydrochloride Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the 1st study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the 2nd study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the 2nd scan and there will be a break between the two scans of approximately 3 hours. For the optional 3rd study scan 4 mg capsule or 30 mL solution standard adult dose of loperamide hydrochloride will be given orally 45-75 minutes prior to the\[11C\]carfentanil injection. Opioid Use Disorder and Medication Assisted Treatment (OUD+/MAT-) Carfentanil, C-11 Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the first study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the second study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the second scan session and there will be a break between the two scan sessions of approximately 3 hours. Opioid Use Disorder Only (OUD+/MAT-) Carfentanil, C-11 Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the first study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the second study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the second scan session and there will be a break between the two scan sessions of approximately 3 hours. Healthy Controls (OUD-) Carfentanil, C-11 Study imaging will be performed using a whole-body PET/CT scanner. Each participant will receive ≤ 10 mCi of \[11C\]carfentanil intravenously (approximate range for most studies is anticipated to be 2-10 mCi ). Participants will undergo dynamic PET/CT imaging of the brain and body. The scan will take approximately 90 minutes for each scan session. Study imaging will be performed using a whole-body PET/CT scanner. For the 1st study scan, participants will receive \[11C\]carfentanil radiotracer alone. For the 2nd study scan approximately 13 mcg/kg of naloxone will be administered by IV prior to the \[11C\]carfentanil injection. If both scans are done the same day, then the naloxone injection will be given before the 2nd scan and there will be a break between the two scans of approximately 3 hours. For the optional 3rd study scan 4 mg capsule or 30 mL solution standard adult dose of loperamide hydrochloride will be given orally 45-75 minutes prior to the\[11C\]carfentanil injection.
- Primary Outcome Measures
Name Time Method MOR BPND measurement - [11C]carfentanil Baseline Measure MOR BPND following the administration of \[11C\]carfentanil alone in 5 brain regions of interest (ROIs) relevant to addiction (the subgenual anterior cingulate, ventral pallidum, amygdala, nucleus accumbens, and dorsal striatum), spinal cord (key role in transmitting pain signals) and organs outside the central nervous system (CNS) that contain mu-opioid receptors (e.g., the gastrointestinal tract, heart).
MOR BPND measurement - naloxone and [11C]carfentanil Follow up - 1 day to 6 weeks Measure MOR BPND following the administration of both naloxone and \[11C\]carfentanil in 5 brain regions of interest (ROIs) relevant to addiction (the subgenual anterior cingulate, ventral pallidum, amygdala, nucleus accumbens, and dorsal striatum), spinal cord (key role in transmitting pain signals) and organs outside the central nervous system (CNS) that contain mu-opioid receptors (e.g., the gastrointestinal tract, heart).
- Secondary Outcome Measures
Name Time Method MOR BPND measurement - loperamide and [11C]carfentanil Follow up - 1 day to 6 weeks Measure MOR BPND following the administration of both oral loperamide hydrochloride (pre-injection) and \[11C\]carfentanil to help develop imaging methods to characterize differential mu-opioid receptor availability in the brain and gut.
Trial Locations
- Locations (1)
University of Pennsylvania, Perelman School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States