Clinical trial NCT04454411: Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder
Official title: Brain Mechanisms of Cognitive Response to Pharmacotherapy in Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Opioid Dependence
Keywords: naltrexone
buprenorphine
neuroimaging
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2020-07-01
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

1. Males and Females
2. 18-65 Years old
3. OUD by DSM5 Criteria, confirmed by history and physical examination including urine toxicology, medical records and self-report
4. Opioids are the drug of choice
5. Interested in injectable extended release agonist or antagonist treatment
6. Have a stable address, working command of English language, and telephone access.
7. Women of childbearing age must use an effective contraceptive

Exclusion Criteria:

1. Psychiatric Co-morbidities:

   1. Lifetime diagnoses of any psychotic disorder, e.g. schizophrenia, schizoaffective disorder, bipolar disorder type 1.
   2. 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.
   3. Polysubstance users whose drug of choice is not opioids.
2. Contraindications for XRNTX or XRBUP e.g. active liver disease.
3. 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
4. Contraindications for MRI, e.g. claustrophobia, indwelling foreign magnetic agents.

Primary outcomes:
measure: Functional Magnetic Resonance Imaging (fMRI) signal
timeFrame: up to 90 days
measure: Urine Toxicology: opioid
timeFrame: Through the study completion, up to 120 days
Secondary outcomes:
measure: Anxiety
timeFrame: Through the study completion, up to 120 days
measure: Depression
timeFrame: Through the study completion, up to 120 days
measure: Non-opioid Urine Toxicology
timeFrame: Through the study completion, up to 120 days
Other outcomes:
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