<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/NCT01733693</url>
  </required_header>
  <id_info>
    <org_study_id>2012-433</org_study_id>
    <secondary_id>1R01DA032552-01A1</secondary_id>
    <nct_id>NCT01733693</nct_id>
  </id_info>
  <brief_title>Neurocognitive Effects of Opiate Agonist Treatment</brief_title>
  <acronym>NEO</acronym>
  <official_title>Neurocognitive Effects of Opiate Agonist Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Albert Einstein College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Drug Abuse (NIDA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Montefiore Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fordham University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Albert Einstein College of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to (1) compare the effects of buprenorphine and methadone, two&#xD;
      types of opioid addiction treatment, on the ability to think and reason among people addicted&#xD;
      to opiates, and who are either HIV negative or HIV positive; and (2) investigate whether HIV&#xD;
      infection changes the way opioid treatment affects the ability to think and reason. The&#xD;
      investigators hypothesize that there will be (1) significant improvement in thinking and&#xD;
      reasoning ability after starting buprenorphine treatment compared to methadone treatment,&#xD;
      among participants with and without HIV at 2 and 4 months compared to baseline; and (2) HIV&#xD;
      positive participants will demonstrate significant improvement in thinking and reasoning&#xD;
      ability at 2 and 4 months compared to baseline, but that their thinking and reasoning ability&#xD;
      will still be lower than HIV negative participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After randomization, each medication will be prescribed and administered by one of these&#xD;
      experienced clinicians, according to well- established national protocols. Participants will&#xD;
      be randomized in a 1:1 ratio in variable size blocks of 4-8 via central, computer-generated&#xD;
      randomization. Given the relatively small sample size, we will randomize in blocks to ensure&#xD;
      comparison groups of approximately equal size. Because medication type will not be blinded,&#xD;
      we will vary block size to prevent anticipation of treatment arm assignment. We will also&#xD;
      stratify randomization by HIV status to ensure equal numbers of HIV-infected persons in each&#xD;
      arm.&#xD;
&#xD;
      INTERVENTION DOSE. Doses of buprenorphine and methadone will be adjusted within pre-specified&#xD;
      ranges to ensure that comparisons between the two treatments are based on individually&#xD;
      optimized doses.&#xD;
&#xD;
      Buprenorphine (we will use the buprenorphine/naloxone combination exclusively) will be&#xD;
      administered at a dose of 8 to 32 mg per day, though we expect most subjects not to exceed 24&#xD;
      mg per day. These doses approximate methadone doses of 60 to 100 mg daily, which are in the&#xD;
      upper range of doses generally used in clinical practice, but are well-known to be most&#xD;
      efficacious and are also most prevalent in DoSA. Since study clinicians will be experienced&#xD;
      substance abuse treatment providers, some flexibility will be allowed within these&#xD;
      parameters. Both buprenorphine and methadone will be administered daily as oral medications.&#xD;
&#xD;
      The study will have two phases: induction/stabilization (weeks 1 - 3) and maintenance (weeks&#xD;
      4 - 24).&#xD;
&#xD;
      During dose induction/stabilization, subjects will attend daily visits (Sx/week) with a study&#xD;
      clinician and receive gradually increasing doses of medication (see below). The first week of&#xD;
      induction/stabilization will be considered a run-in period; at the conclusion of this week&#xD;
      participants will complete enrollment in the trial and also complete their first NP research&#xD;
      visit. The purpose of the run-in period is to ensure that we enroll persons who are able to&#xD;
      comply with all trial requirements.&#xD;
&#xD;
      MAINTENANCE PHASE. The maintenance stage of opioid pharmacotherapy begins when a patient is&#xD;
      responding optimally to medication treatment and routine dosage adjustments are no longer&#xD;
      needed. Patients at this stage have stopped abusing opioids and many remain on the same&#xD;
      dosage of treatment medication for many months, whereas others require frequent or occasional&#xD;
      adjustments. During maintenance (starting on day 22, week 4),subjects in both arms will&#xD;
      attend the clinic three times per week, on Monday, Wednesday, and Friday, and will receive&#xD;
      bottles of medication to take home for the other four days of the week. Subjects will receive&#xD;
      increases in their doses starting in week 4 if they meet pre-established criteria, up to 100&#xD;
      mg of methadone, and up to 32 mg of buprenorphine.&#xD;
&#xD;
      Our proposed research plan includes two follow-up visits, three and six months after the&#xD;
      baseline visit. We anticipate that subjects will still be in the maintenance phase at the&#xD;
      time of both these visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Global Neurocognitive Function</measure>
    <time_frame>2 and 4 months</time_frame>
    <description>Metrics:&#xD;
A Global Deficit Score (GDS) is computed by adding deficit ratings of the component test measures, and dividing by total number of measures. (Please see list of component test measures under the Domain-Specific Neurocognitive Function outcome).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Domain-Specific Neurocognitive Function (i.e. in the domains of executive functioning, learning, memory, attention/working memory, processing speed, motor, and verbal functioning).</measure>
    <time_frame>2 and 4 months</time_frame>
    <description>Metrics:&#xD;
Domain Deficit Scores (DDS) are created for each of the 7 cognitive ability domains. Deficit Scores can be analyzed as dichotomous variables to classify individual subjects as impaired or normal, or continuously.&#xD;
Executive Functioning -- Wisconsin Card Sorting Task-64 Item Version; Trail Making Test (Part B)&#xD;
Learning -- Hopkins Verbal Learning Test-Revised (Total Recall); Brief Visuospatial Memory Test-Revised (Total Recall)&#xD;
Memory -- Hopkins Verbal Learning Test (Delayed Recall Trial); Brief Visuospatial Memory Test-Revised (Delayed Recall Trial)&#xD;
Attention/Working Memory -- WAIS-III Letter Number Sequencing; PASAT Total Correct&#xD;
Processing Speed -- WAIS-III Digit Symbol; WAIS-III Symbol Search; Trail Making Test (Part A)&#xD;
Motor -- Grooved Pegboard Time (dominant hand); Grooved Pegboard Time (non-dominant hand)]&#xD;
Verbal Functioning -- Controlled Oral Word Association Test (F-A-S); Semantic (Animal) Fluency</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">135</enrollment>
  <condition>Opioid-Related Disorders</condition>
  <condition>HIV</condition>
  <condition>HIV Infections</condition>
  <arm_group>
    <arm_group_label>Buprenorphine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral sublingual tablet, 8-32 mg per day, administered daily for duration of 4 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methadone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral sublingual tablet, 60-100 mg per day, administered daily for duration of 4 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Buprenorphine</intervention_name>
    <description>Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.</description>
    <arm_group_label>Buprenorphine</arm_group_label>
    <other_name>Buprenorphine HCl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methadone</intervention_name>
    <description>Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.</description>
    <arm_group_label>Methadone</arm_group_label>
    <other_name>Methadone Hydrochloride</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 - 68&#xD;
&#xD;
          -  English or Spanish speaking&#xD;
&#xD;
          -  Documentation of HIV Status&#xD;
&#xD;
          -  Opioid-dependent without having received medication treatment for opioid dependence&#xD;
             within the previous 90 days&#xD;
&#xD;
          -  Negative pregnancy test, for women&#xD;
&#xD;
          -  No &quot;street&quot; use of methadone or buprenorphine&#xD;
&#xD;
          -  Willing to participate in all study components&#xD;
&#xD;
          -  Able to provide informed consent&#xD;
&#xD;
          -  Education &gt; 6 years&#xD;
&#xD;
          -  Not acutely intoxicated&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Serious or unstable medical disease: liver disease (AST or ALT ≥ 3x ULN, elevated&#xD;
             PT/INR, albumin &lt;3.0 g/dl or evidence of decompensated cirrhosis);&#xD;
&#xD;
          -  Severe cardiovascular disease (MI, PTCA, unstable angina, CABG, and/or serious&#xD;
             arrhythmia in the previous 6 months);&#xD;
&#xD;
          -  COPD (requiring supplemental oxygen or hospitalization in past 6 months);&#xD;
&#xD;
          -  End stage renal disease or creatinine clearance &lt;30 mL/min&#xD;
&#xD;
          -  Neurological disease: head injury with LOC&gt;24 hour, previous penetrating skull wound,&#xD;
             focal brain lesion, history of neurosurgery, seizure disorder (not ETOH-related),&#xD;
             non-HIV CNS opportunistic infection&#xD;
&#xD;
          -  Psychiatric disorders (schizophrenia or bipolar)&#xD;
&#xD;
          -  Benzodiazepine or alcohol dependence&#xD;
&#xD;
          -  Chronic pain conditions requiring opioid analgesics&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>68 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Julia Arnsten, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Montefiore Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fordham University</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albert Einstein College of Medicine of Yeshiva University</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>November 14, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 27, 2012</study_first_posted>
  <last_update_submitted>January 28, 2022</last_update_submitted>
  <last_update_submitted_qc>January 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Albert Einstein College of Medicine</investigator_affiliation>
    <investigator_full_name>Julia H. Arnsten</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Buprenorphine</keyword>
  <keyword>Methadone</keyword>
  <keyword>Cognition</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>Buprenorphine</mesh_term>
    <mesh_term>Methadone</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01733693
org study id: 2012-433
secondary id: 1R01DA032552-01A1
nct id: NCT01733693
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to (1) compare the effects of buprenorphine and methadone, two
      types of opioid addiction treatment, on the ability to think and reason among people addicted
      to opiates, and who are either HIV negative or HIV positive; and (2) investigate whether HIV
      infection changes the way opioid treatment affects the ability to think and reason. The
      investigators hypothesize that there will be (1) significant improvement in thinking and
      reasoning ability after starting buprenorphine treatment compared to methadone treatment,
      among participants with and without HIV at 2 and 4 months compared to baseline; and (2) HIV
      positive participants will demonstrate significant improvement in thinking and reasoning
      ability at 2 and 4 months compared to baseline, but that their thinking and reasoning ability
      will still be lower than HIV negative participants.
After randomization, each medication will be prescribed and administered by one of these
      experienced clinicians, according to well- established national protocols. Participants will
      be randomized in a 1:1 ratio in variable size blocks of 4-8 via central, computer-generated
      randomization. Given the relatively small sample size, we will randomize in blocks to ensure
      comparison groups of approximately equal size. Because medication type will not be blinded,
      we will vary block size to prevent anticipation of treatment arm assignment. We will also
      stratify randomization by HIV status to ensure equal numbers of HIV-infected persons in each
      arm.

      INTERVENTION DOSE. Doses of buprenorphine and methadone will be adjusted within pre-specified
      ranges to ensure that comparisons between the two treatments are based on individually
      optimized doses.

      Buprenorphine (we will use the buprenorphine/naloxone combination exclusively) will be
      administered at a dose of 8 to 32 mg per day, though we expect most subjects not to exceed 24
      mg per day. These doses approximate methadone doses of 60 to 100 mg daily, which are in the
      upper range of doses generally used in clinical practice, but are well-known to be most
      efficacious and are also most prevalent in DoSA. Since study clinicians will be experienced
      substance abuse treatment providers, some flexibility will be allowed within these
      parameters. Both buprenorphine and methadone will be administered daily as oral medications.

      The study will have two phases: induction/stabilization (weeks 1 - 3) and maintenance (weeks
      4 - 24).

      During dose induction/stabilization, subjects will attend daily visits (Sx/week) with a study
      clinician and receive gradually increasing doses of medication (see below). The first week of
      induction/stabilization will be considered a run-in period; at the conclusion of this week
      participants will complete enrollment in the trial and also complete their first NP research
      visit. The purpose of the run-in period is to ensure that we enroll persons who are able to
      comply with all trial requirements.

      MAINTENANCE PHASE. The maintenance stage of opioid pharmacotherapy begins when a patient is
      responding optimally to medication treatment and routine dosage adjustments are no longer
      needed. Patients at this stage have stopped abusing opioids and many remain on the same
      dosage of treatment medication for many months, whereas others require frequent or occasional
      adjustments. During maintenance (starting on day 22, week 4),subjects in both arms will
      attend the clinic three times per week, on Monday, Wednesday, and Friday, and will receive
      bottles of medication to take home for the other four days of the week. Subjects will receive
      increases in their doses starting in week 4 if they meet pre-established criteria, up to 100
      mg of methadone, and up to 32 mg of buprenorphine.

      Our proposed research plan includes two follow-up visits, three and six months after the
      baseline visit. We anticipate that subjects will still be in the maintenance phase at the
      time of both these visits.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Global Neurocognitive Function
time frame: 2 and 4 months
description: Metrics:
A Global Deficit Score (GDS) is computed by adding deficit ratings of the component test measures, and dividing by total number of measures. (Please see list of component test measures under the Domain-Specific Neurocognitive Function outcome).
measure: Domain-Specific Neurocognitive Function (i.e. in the domains of executive functioning, learning, memory, attention/working memory, processing speed, motor, and verbal functioning).
time frame: 2 and 4 months
description: Metrics:
Domain Deficit Scores (DDS) are created for each of the 7 cognitive ability domains. Deficit Scores can be analyzed as dichotomous variables to classify individual subjects as impaired or normal, or continuously.
Executive Functioning -- Wisconsin Card Sorting Task-64 Item Version; Trail Making Test (Part B)
Learning -- Hopkins Verbal Learning Test-Revised (Total Recall); Brief Visuospatial Memory Test-Revised (Total Recall)
Memory -- Hopkins Verbal Learning Test (Delayed Recall Trial); Brief Visuospatial Memory Test-Revised (Delayed Recall Trial)
Attention/Working Memory -- WAIS-III Letter Number Sequencing; PASAT Total Correct
Processing Speed -- WAIS-III Digit Symbol; WAIS-III Symbol Search; Trail Making Test (Part A)
Motor -- Grooved Pegboard Time (dominant hand); Grooved Pegboard Time (non-dominant hand)]
Verbal Functioning -- Controlled Oral Word Association Test (F-A-S); Semantic (Animal) Fluency
arm group label: Buprenorphine
arm group type: Experimental
description: Oral sublingual tablet, 8-32 mg per day, administered daily for duration of 4 months
arm group label: Methadone
arm group type: Active Comparator
description: Oral sublingual tablet, 60-100 mg per day, administered daily for duration of 4 months
intervention type: Drug
intervention name: Buprenorphine
description: Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.
arm group label: Buprenorphine
other name: Buprenorphine HCl
intervention type: Drug
intervention name: Methadone
description: Study participants will be randomly assigned 1:1 to buprenorphine (experimental/intervention) or methadone (active comparator). We will stratify by HIV status to ensure an equal number of HIV-infected participants in each group.
arm group label: Methadone
other name: Methadone Hydrochloride
criteria: 
gender: All
minimum age: 18 Years
maximum age: 68 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Julia Arnsten, MD, MPH
role: Principal Investigator
affiliation: Montefiore Medical Center
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Albert Einstein College of Medicine
investigator full name: Julia H. Arnsten
investigator title: Principal Investigator
mesh term: Opioid-Related Disorders
mesh term: Buprenorphine
mesh term: Methadone