Multi-System Analysis of Opioid Receptor Binding

Healthy Clinical Trial

Official title:

Pilot Study of a Multi-System Analysis of Opioid Receptor Binding

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05528848
• Other study ID #: 851051
• Status: Recruiting
• Phase: Phase 1
• Start date: September 20, 2022
• Est. completion date: September 2025

Study information

• Verified date: August 2023
• Source: University of Pennsylvania
• Contact: Erin Schubert
• Phone: 215-573-6569
• Email: erinshu[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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 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.

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.

Subjects are required to have had a brain MRI performed within 1 year prior to study enrollment, 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 information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria

Cohort 1 (OUD+/MAT+):

1. 18-50 years of age

2. Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

3. Fluent in English and able to provide written informed consent in English.

4. OUD positive (+): Participants will meet DSM-5 criteria for a lifetime diagnosis of OUD and will be on a stable dosage of buprenorphine or methadone treatment for at least four weeks prior to the screening visit.

Cohort 2 (OUD+/MAT-):

1. 18-50 years of age

2. Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

3. Fluent in English and able to provide written informed consent in English.

4. OUD positive (+): Participants will meet DSM-5 criteria for a lifetime diagnosis of OUD, but cannot meet criteria for OUD in the 2 months prior to screening, has not used an opioid for any reason in the 30 days prior to screening as evidenced by self-report, medical record review, and urine drug testing at screening and and on the day of the PET scan, and has not received MAT for OUD during the 12 months prior to screening.

Cohort 3 (OUD-, Healthy Controls):

1. Healthy males and females, 18-50 years of age

2. Informed of the investigational nature of this study and able to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

3. Fluent in English and able to provide written informed consent in English.

4. OUD negative (-): Must never have met criteria for OUD (as per DSM-5) and cannot have used an opioid for any reason in the past 30 days prior to screening as evidenced by self-report, medical record review, and urine drug testing at screening.

Exclusion Criteria

Cohort 1 (OUD+/MAT+):

1. Women who are pregnant or breast feeding will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.

2. Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.

3. Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.

4. Current major DSM-5 Axis 1 psychiatric diagnosis that requires treatment with a medication that interferes with opioid receptor binding, as identified during psychiatric interview or mental status examination at screening/baseline.

5. History of epilepsy or seizure disorder, head trauma or brain (CNS) tumor as assessed by medical record review and/or self-report

6. Current severe substance use disorder (SUD) other than OUD and /or current pharmacological treatment for an SUD other than OUD, including nicotine dependence, that would interfere with study procedures and outcome.

7. A breath alcohol concentration (BAC) reading > 0.01 or a urine toxicology test positive for prohibited drugs.

8. Current use or recent discontinuation (within 14 days of screening) of medications that interfere with radiotracer binding. Participants will be instructed to refrain from using any study-prohibited drugs, though participants will be allowed to take prescription medicines that are not exclusionary throughout their participation in the study.

9. Allergic reaction to any opioid or naloxone

10. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician

11. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-report that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study or interfere with distribution of the radiotracer.

Cohort 2 (OUD+/MAT-):

1. Women who are pregnant or breast feeding are not eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.

2. Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.

3. Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.

4. Current major DSM-5 Axis 1 psychiatric diagnosis requiring medications that interfere with radiotracer binding, as identified during a psychiatric interview or mental status examination at screening/baseline.

5. History of epilepsy or seizure disorder, head trauma or brain (CNS) tumor as assessed by medical record review and/or self-report

6. Current severe substance use disorder (SUD) other than OUD and /or current treatment for an SUD other than OUD, including nicotine dependence, that would interfere with study procedures and outcome.

7. A breath alcohol concentration (BAC) reading > 0.01, a urine toxicology test positive for prohibited drugs.

8. Current use or use within the past 12 months of any medications containing naltrexone or other MOR ligands (e.g., buprenorphine, methadone)

9. Use within the month prior to screening of any antipsychotic, anticonvulsant, or stimulant medication or any other medication that is deemed by a physician investigator to potentially interfere with carfentanil binding at the MOR.

10. Allergic reaction to any opioid or naloxone

11. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician

12. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-report that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study or interfere with distribution of the radiotracer.

Cohort 3 (Healthy Controls):

1. Women who are pregnant or breast feeding will not be eligible for this study; a urine pregnancy test will be performed in women of child-bearing potential at screening and on the day of each of the PET/CT scans.

2. Subjects who report claustrophobia, which in the opinion of an investigator would interfere with acquisition of the structural MRI required for PET co-registration, and/or the PET scan itself.

3. Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible). An MRI screening form will be completed during screening.

4. History of or current major DSM-5 Axis 1 psychiatric diagnosis, as identified during psychiatric interview or mental status examination at screening/baseline.

5. History of epilepsy or seizure disorder, head trauma or brain (CNS) tumor as assessed by medical record review and/or self-report

6. A history of substance use disorder (SUD) and /or current treatment for a SUD, including nicotine dependence.

7. Self-reported current alcohol consumption that exceeds 14 standard drinks/week for men and 7 standard drinks/week for women.

8. A breath alcohol concentration (BAC) reading > 0.01 or a urine toxicology test positive for prohibited drugs.

9. Current use or use within the past 12 months of any medications containing naltrexone or other MOR ligands (e.g., buprenorphine, methadone)

10. Current use or use within the past 12 months of medications that could interfere with radiotracer binding. (Participants will be instructed to refrain from using any study-prohibited drugs, though participants will be allowed to take prescription medicines that are not exclusionary throughout their participation in the study.)

11. Any form of smoking cessation medication

12. Any medication prescribed to treat alcohol use disorder or heavy drinking

13. Use within the past 12 months of psychotropic medications (antipsychotics, antidepressants, anti-anxiety medications, stimulants or opioid-containing medications for pain for longer than one week).

14. Allergic reaction to any opioid or naloxone

15. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician

16. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-report that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study or interfere with distribution of the radiotracer.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Carfentanil, C-11
Investigational radiotracer to be injected by IV as s a bolus during both study PET/CT scans.
• Naloxone
Non-selective opioid antagonist injected by IV parenterally during the second study PET/CT scan only.

Locations

Country	Name	City	State
United States	University of Pennsylvania, Perelman School of Medicine	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MOR BPND measurement - [11C]carfentanil	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).	Baseline
Primary	MOR BPND measurement - naloxone and [11C]carfentanil	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).	Follow up - 1 day to 6 weeks