Back to resultsBrain Mechanisms of Pharmacotherapy in Opioid Use Disorder
Primary Purpose
Opioid Dependence
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Brixadi
Vivitrol
Sponsored by
About this trial
This is an interventional basic science trial for Opioid Dependence focused on measuring naltrexone, buprenorphine, neuroimaging
Eligibility Criteria
Inclusion Criteria:
- Males and Females
- 18-65 Years old
- OUD by DSM5 Criteria, confirmed by history and physical examination including urine toxicology, medical records and self-report
- Opioids are the drug of choice
- Interested in injectable extended release agonist or antagonist treatment
- Have a stable address, working command of English language, and telephone access.
- Women of childbearing age must use an effective contraceptive
Exclusion Criteria:
Psychiatric Co-morbidities:
- Lifetime diagnoses of any psychotic disorder, e.g. schizophrenia, schizoaffective disorder, bipolar disorder type 1.
- Psychiatric Co-morbidities: Psychiatric disorders requiring current medication treatment, e.g. moderate to severe depression. Mild to moderate Depressive and Anxiety disorders and Attention Deficit Hyperactivity Disorder that do not require prescription stimulants and DSM5 Cluster B and C personality disorders are also allowed.
- Polysubstance users whose drug of choice is not opioids.
- Contraindications for XRNTX or XRBUP e.g. active liver disease.
- Medical and surgical conditions such as malignancy that may affect patients' ability to receive XRNTX or XRBUP treatment because it may interfere with opioid analgesia
- Contraindications for MRI, e.g. claustrophobia, indwelling foreign magnetic agents.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Buprenorphine
Naltrexone
Arm Description
Participants assigned to treatment with extended-release buprenorphine
Participants assigned to treatment with extended-release naltrexone
Outcomes
Primary Outcome Measures
Functional Magnetic Resonance Imaging (fMRI) signal
Brain fMRI response to neurocognitive probes
Urine Toxicology: opioid
Rapid semi-quantitative ELISA urine drug screen test for morphine, oxycodone and methadone, followed by (cut off levels):
Methadone (MTD) Methadone 300 ng/mL Opiates (OPI 300) Morphine Morphine **300 ng/mL Oxycodone (OXY) Oxycodone 100 ng/mL
Secondary Outcome Measures
Anxiety
Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1967). The HAM-A is a 15-minute, 14-item, clinician-administered instrument that measures current anxiety and changes in anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Depression
Hamilton Depression Rating Scale (HAM-D) (Hamilton, 1959 #2497). The HAM-D is a 20-minute, 24-item interview that measures the severity of depression and changes in depressive symptoms. HAM-D form includes 21 items, however the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. The HAM-D score level corresponds to the clinical severity of depression as follows: 10 - 13 mild; 14-17 mild to moderate; >17 moderate to severe.
Non-opioid Urine Toxicology
Rapid semi-quantitative ELISA urine drug screen test for amphetamine/methamphetamine, benzodiazepines, cocaine, phencyclidine, cannabinoids and cotinine, with cut off levels:
Amphetamine/Methamphetamine 500/1000ng/ml Benzodiazepines Enzyme Immunoassay (EIA) 200 ng/mL Cocaine Metabolite (Benzoylecgonine) EIA 150/300 ng/mL Cotinine EIA 250 ng/mL Phencyclidine EIA 25 ng/mL THC (Cannabinoids) EIA 20/50 ng/mL*
Full Information
NCT ID
NCT04454411
First Posted
June 18, 2020
Last Updated
October 9, 2023
Sponsor
University of Pennsylvania
1. Study Identification
Unique Protocol Identification Number
NCT04454411
Brief Title
Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder
Official Title
Brain Mechanisms of Cognitive Response to Pharmacotherapy in Opioid Use Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
February 1, 2025 (Anticipated)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
January 1, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will investigate the mechanisms of cognitive-behavioral response to medications used for relapse prevention in opioid use disorder (opioid addiction, OUD), through investigation of the neural circuits underlying key cognition functions. The study will use previously validated cognitive probes, functional Magnetic Resonance Imaging (fMRI), and novel extended-release injectable preparations of opioid partial agonist buprenorphine and antagonist naltrexone, in OUD patients to explain the individual heterogeneity of OUD treatment response.
Detailed Description
This proposal seeks to identify the neural circuits underlying the cognitive effects of medication assisted therapy (MAT) for OUD. The study will examine the neurocognitive effects of MAT by comparing two preparations with different pharmacodynamic properties (extended release buprenorphine and naltrexone, XRBUP, XRNTX) in three key domains (incentive salience, executive functioning, and emotion processing) using task functional Magnetic Resonance Imaging (MRI). In the 1st phase of the study, forty treatment-seeking OUD patients will be randomized to XRNTX or XRBUP groups after detoxification. Participants will undergo medication induction followed by monthly injections and urine toxicology monitoring for 120 days. Neuroimaging will follow completion of detoxification (pre-treatment) and 15 days after the second injection (on-treatment). The second study phase will extend the paradigm to an independent sample of 160 additional participants and test the explanatory value of MAT-induced changes in the neuroimaging signal in the classification of OUD treatment outcomes.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Dependence
Keywords
naltrexone, buprenorphine, neuroimaging
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Buprenorphine
Arm Type
Experimental
Arm Description
Participants assigned to treatment with extended-release buprenorphine
Arm Title
Naltrexone
Arm Type
Active Comparator
Arm Description
Participants assigned to treatment with extended-release naltrexone
Intervention Type
Drug
Intervention Name(s)
Brixadi
Other Intervention Name(s)
Buprenorphine Injectable Product
Intervention Description
Extended release injectable Buprenorphine
Intervention Type
Drug
Intervention Name(s)
Vivitrol
Other Intervention Name(s)
Naltrexone Injectable Product
Intervention Description
Extended release injectable Naltrexone
Primary Outcome Measure Information:
Title
Functional Magnetic Resonance Imaging (fMRI) signal
Description
Brain fMRI response to neurocognitive probes
Time Frame
up to 90 days
Title
Urine Toxicology: opioid
Description
Rapid semi-quantitative ELISA urine drug screen test for morphine, oxycodone and methadone, followed by (cut off levels):
Methadone (MTD) Methadone 300 ng/mL Opiates (OPI 300) Morphine Morphine **300 ng/mL Oxycodone (OXY) Oxycodone 100 ng/mL
Time Frame
Through the study completion, up to 120 days
Secondary Outcome Measure Information:
Title
Anxiety
Description
Hamilton Anxiety Rating Scale (HAM-A) (Hamilton, 1967). The HAM-A is a 15-minute, 14-item, clinician-administered instrument that measures current anxiety and changes in anxiety symptoms. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Time Frame
Through the study completion, up to 120 days
Title
Depression
Description
Hamilton Depression Rating Scale (HAM-D) (Hamilton, 1959 #2497). The HAM-D is a 20-minute, 24-item interview that measures the severity of depression and changes in depressive symptoms. HAM-D form includes 21 items, however the scoring is based on the first 17. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. The HAM-D score level corresponds to the clinical severity of depression as follows: 10 - 13 mild; 14-17 mild to moderate; >17 moderate to severe.
Time Frame
Through the study completion, up to 120 days
Title
Non-opioid Urine Toxicology
Description
Rapid semi-quantitative ELISA urine drug screen test for amphetamine/methamphetamine, benzodiazepines, cocaine, phencyclidine, cannabinoids and cotinine, with cut off levels:
Amphetamine/Methamphetamine 500/1000ng/ml Benzodiazepines Enzyme Immunoassay (EIA) 200 ng/mL Cocaine Metabolite (Benzoylecgonine) EIA 150/300 ng/mL Cotinine EIA 250 ng/mL Phencyclidine EIA 25 ng/mL THC (Cannabinoids) EIA 20/50 ng/mL*
Time Frame
Through the study completion, up to 120 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Males and Females
18-65 Years old
OUD by DSM5 Criteria, confirmed by history and physical examination including urine toxicology, medical records and self-report
Opioids are the drug of choice
Interested in injectable extended release agonist or antagonist treatment
Have a stable address, working command of English language, and telephone access.
Women of childbearing age must use an effective contraceptive
Exclusion Criteria:
Psychiatric Co-morbidities:
Lifetime diagnoses of any psychotic disorder, e.g. schizophrenia, schizoaffective disorder, bipolar disorder type 1.
Psychiatric Co-morbidities: Psychiatric disorders requiring current medication treatment, e.g. moderate to severe depression. Mild to moderate Depressive and Anxiety disorders and Attention Deficit Hyperactivity Disorder that do not require prescription stimulants and DSM5 Cluster B and C personality disorders are also allowed.
Polysubstance users whose drug of choice is not opioids.
Contraindications for XRNTX or XRBUP e.g. active liver disease.
Medical and surgical conditions such as malignancy that may affect patients' ability to receive XRNTX or XRBUP treatment because it may interfere with opioid analgesia
Contraindications for MRI, e.g. claustrophobia, indwelling foreign magnetic agents.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Langleben, M.D.
Phone
215-746-0107
Email
langlebe@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
James Padley
Phone
847-209-9619
Email
jamespadley5@gmail.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder
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