<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04454411</url>
  </required_header>
  <id_info>
    <nct_id>NCT04454411</nct_id>
  </id_info>
  <brief_title>Brain Mechanisms of Pharmacotherapy in Opioid Use Disorder</brief_title>
  <official_title>Brain Mechanisms of Cognitive Response to Pharmacotherapy in Opioid Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Pennsylvania</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate the mechanisms of cognitive-behavioral response to medications&#xD;
      used for relapse prevention in opioid use disorder (opioid addiction, OUD), through&#xD;
      investigation of the neural circuits underlying key cognition functions. The study will use&#xD;
      previously validated cognitive probes, functional Magnetic Resonance Imaging (fMRI), and&#xD;
      novel extended-release injectable preparations of opioid partial agonist buprenorphine and&#xD;
      antagonist naltrexone, in OUD patients to explain the individual heterogeneity of OUD&#xD;
      treatment response.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This proposal seeks to identify the neural circuits underlying the cognitive effects of&#xD;
      medication assisted therapy (MAT) for OUD. The study will examine the neurocognitive effects&#xD;
      of MAT by comparing two preparations with different pharmacodynamic properties (extended&#xD;
      release buprenorphine and naltrexone, XRBUP, XRNTX) in three key domains (incentive salience,&#xD;
      executive functioning, and emotion processing) using task functional Magnetic Resonance&#xD;
      Imaging (MRI). In the 1st phase of the study, forty treatment-seeking OUD patients will be&#xD;
      randomized to XRNTX or XRBUP groups after detoxification. Participants will undergo&#xD;
      medication induction followed by monthly injections and urine toxicology monitoring for 120&#xD;
      days. Neuroimaging will follow completion of detoxification (pre-treatment) and 15 days after&#xD;
      the second injection (on-treatment). The second study phase will extend the paradigm to an&#xD;
      independent sample of 160 additional participants and test the explanatory value of&#xD;
      MAT-induced changes in the neuroimaging signal in the classification of OUD treatment&#xD;
      outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">February 1, 2023</start_date>
  <completion_date type="Anticipated">January 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2026</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Functional Magnetic Resonance Imaging (fMRI) signal</measure>
    <time_frame>up to 90 days</time_frame>
    <description>Brain fMRI response to neurocognitive probes</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Urine Toxicology: opioid</measure>
    <time_frame>Through the study completion, up to 120 days</time_frame>
    <description>Rapid semi-quantitative ELISA urine drug screen test for morphine, oxycodone and methadone, followed by (cut off levels):&#xD;
Methadone (MTD) Methadone 300 ng/mL Opiates (OPI 300) Morphine Morphine **300 ng/mL Oxycodone (OXY) Oxycodone 100 ng/mL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anxiety</measure>
    <time_frame>Through the study completion, up to 120 days</time_frame>
    <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 &lt;17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Depression</measure>
    <time_frame>Through the study completion, up to 120 days</time_frame>
    <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; &gt;17 moderate to severe.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Non-opioid Urine Toxicology</measure>
    <time_frame>Through the study completion, up to 120 days</time_frame>
    <description>Rapid semi-quantitative ELISA urine drug screen test for amphetamine/methamphetamine, benzodiazepines, cocaine, phencyclidine, cannabinoids and cotinine, with cut off levels:&#xD;
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*</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Opioid Dependence</condition>
  <arm_group>
    <arm_group_label>Buprenorphine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants assigned to treatment with extended-release buprenorphine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Naltrexone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants assigned to treatment with extended-release naltrexone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Brixadi</intervention_name>
    <description>Extended release injectable Buprenorphine</description>
    <arm_group_label>Buprenorphine</arm_group_label>
    <other_name>Buprenorphine Injectable Product</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vivitrol</intervention_name>
    <description>Extended release injectable Naltrexone</description>
    <arm_group_label>Naltrexone</arm_group_label>
    <other_name>Naltrexone Injectable Product</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and Females&#xD;
&#xD;
          2. 18-65 Years old&#xD;
&#xD;
          3. OUD by DSM5 Criteria, confirmed by history and physical examination including urine&#xD;
             toxicology, medical records and self-report&#xD;
&#xD;
          4. Opioids are the drug of choice&#xD;
&#xD;
          5. Interested in injectable extended release agonist or antagonist treatment&#xD;
&#xD;
          6. Have a stable address, working command of English language, and telephone access.&#xD;
&#xD;
          7. Women of childbearing age must use an effective contraceptive&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Psychiatric Co-morbidities:&#xD;
&#xD;
               1. Lifetime diagnoses of any psychotic disorder, e.g. schizophrenia, schizoaffective&#xD;
                  disorder, bipolar disorder type 1.&#xD;
&#xD;
               2. Psychiatric Co-morbidities: Psychiatric disorders requiring current medication&#xD;
                  treatment, e.g. moderate to severe depression. Mild to moderate Depressive and&#xD;
                  Anxiety disorders and Attention Deficit Hyperactivity Disorder that do not&#xD;
                  require prescription stimulants and DSM5 Cluster B and C personality disorders&#xD;
                  are also allowed.&#xD;
&#xD;
               3. Polysubstance users whose drug of choice is not opioids.&#xD;
&#xD;
          2. Contraindications for XRNTX or XRBUP e.g. active liver disease.&#xD;
&#xD;
          3. Medical and surgical conditions such as malignancy that may affect patients' ability&#xD;
             to receive XRNTX or XRBUP treatment because it may interfere with opioid analgesia&#xD;
&#xD;
          4. Contraindications for MRI, e.g. claustrophobia, indwelling foreign magnetic agents.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Daniel Langleben, M.D.</last_name>
    <phone>215-746-0107</phone>
    <email>langlebe@pennmedicine.upenn.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>James Padley</last_name>
    <phone>847-209-9619</phone>
    <email>jamespadley5@gmail.com</email>
  </overall_contact_backup>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>naltrexone</keyword>
  <keyword>buprenorphine</keyword>
  <keyword>neuroimaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naltrexone</mesh_term>
    <mesh_term>Buprenorphine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04454411
nct id: NCT04454411
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Functional Magnetic Resonance Imaging (fMRI) signal
time frame: up to 90 days
description: Brain fMRI response to neurocognitive probes
measure: Urine Toxicology: opioid
time frame: Through the study completion, up to 120 days
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
measure: Anxiety
time frame: Through the study completion, up to 120 days
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.
measure: Depression
time frame: Through the study completion, up to 120 days
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.
measure: Non-opioid Urine Toxicology
time frame: Through the study completion, up to 120 days
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*
arm group label: Buprenorphine
arm group type: Experimental
description: Participants assigned to treatment with extended-release buprenorphine
arm group label: Naltrexone
arm group type: Active Comparator
description: Participants assigned to treatment with extended-release naltrexone
intervention type: Drug
intervention name: Brixadi
description: Extended release injectable Buprenorphine
arm group label: Buprenorphine
other name: Buprenorphine Injectable Product
intervention type: Drug
intervention name: Vivitrol
description: Extended release injectable Naltrexone
arm group label: Naltrexone
other name: Naltrexone Injectable Product
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Daniel Langleben, M.D.
phone: 215-746-0107
email: langlebe@pennmedicine.upenn.edu
last name: James Padley
phone: 847-209-9619
email: jamespadley5@gmail.com
responsible party type: Sponsor
mesh term: Opioid-Related Disorders
mesh term: Naltrexone
mesh term: Buprenorphine
sharing ipd: No