xml: <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/NCT06005662</url>
    </required_header>
    <id_info>
      <org_study_id>IRB00344281</org_study_id>
      <nct_id>NCT06005662</nct_id>
    </id_info>
    <brief_title>Inpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder</brief_title>
    <acronym>BIPOD-In</acronym>
    <official_title>Inpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder: a Randomized Double-blind Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Johns Hopkins University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Johns Hopkins University</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study will examine the effect of a single high dose of psilocybin therapy (30 mg) versus&#xD;
        a very low dose (1 mg) as an adjunctive therapy to individuals undergoing standard-of-care&#xD;
        buprenorphine treatment for Opioid use disorder (OUD). Effects of adjunctive psilocybin will&#xD;
        be determined for longitudinal outcomes of opioid abstinence, compliance with buprenorphine&#xD;
        maintenance, quality of life, and mood.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose&#xD;
        psilocybin (30 mg) session compared to a very low dose session (1 mg) following&#xD;
        standard-of-care buprenorphine induction on drug abstinence, quality of life, craving,&#xD;
        tobacco use, and treatment retention in healthy participants with an active OUD diagnosis.&#xD;
        Use of buprenorphine follow standard of care, and the investigators are investigating the&#xD;
        additive power of adjunctive psilocybin to enhance opioid abstinence, treatment adherence,&#xD;
        quality of life, and mood.&#xD;
  &#xD;
        The study will consist of a brief (6-8 day) inpatient phase for standard buprenorphine&#xD;
        induction as well as experimental psilocybin administration, an 8-week outpatient phase&#xD;
        involving standard buprenorphine maintenance and experimental follow-up meetings, and&#xD;
        long-term follow-up sessions for 4 months after. During the inpatient phase, participants&#xD;
        will be inducted onto sublingual (SL) buprenorphine (using a buprenorphine/naloxone&#xD;
        combination product) while admitted to the Bayview Clinical Research Unit. During this time,&#xD;
        participants will also undergo 2-3 preparatory sessions, and will undergo an experimental&#xD;
        drug administration session under supportive conditions, during which the participants will&#xD;
        receive either a very low dose (1 mg) or a single high (30mg) oral dose of psilocybin under&#xD;
        double-blind conditions. At the end of the inpatient phase, participants will be discharged&#xD;
        to complete the 8-week outpatient phase, during which participants will undergo visits at 1,&#xD;
        2, 3, 4, 6, and 8 weeks post-dosing session for monitoring of adverse events, clinical&#xD;
        status, treatment adherence, and to receive a weekly supply of buprenorphine. All&#xD;
        buprenorphine procedures will be open label and will follow standard-of-care practices.&#xD;
  &#xD;
        This trial utilizes a Bayesian sequential methodology, employing a maximum sample size of 90&#xD;
        participants and calculating Bayes factors (starting at 20 participants and assessed after&#xD;
        each 10) to assess evidence for the null and experimental hypotheses, enabling potential&#xD;
        early stopping for efficacy or futility based on predetermined thresholds (Bayes factor of 6&#xD;
        and 1/6). This will be calculated for the primary outcome of opioid abstinence at 8-weeks&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">July 2025</completion_date>
    <primary_completion_date type="Anticipated">July 2025</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>
      <intervention_model_description>The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Participants and study team will be masked/blinded to intervention.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Opioid Abstinence</measure>
      <time_frame>up to 8 weeks</time_frame>
      <description>Non-buprenorphine opioid abstinence as verified by urine toxicology at each visit and Timeline Follow Back (TLFB). These will be combined to assess opioid abstinence for each participant. These will be assessed at the 8-week timepoint for the previous 3-weeks. Missing values will be presumed positive.&#xD;
  Timeline Follow Back (TLFB) for Opioids: This is a self-report of drug use per day. This procedure asks participants to retrospectively quantitate their use of drugs. Greater numbers indicate more days using a substance, smaller numbers or zeros mean less or no days using a substance&#xD;
  Urine toxicology: Urine samples will be collected at each study visit and screened broadly for illicit drug use including opioids via an outside medical laboratory. Quantitative buprenorphine levels will also be collected following induction to gauge whether buprenorphine is being taken.&#xD;
  These measurements will be combined to report the number of participants who were abstinent from opioids.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Treatment Retention</measure>
      <time_frame>8 weeks</time_frame>
      <description>Treatment retention at 8 weeks, as indicated by participants making all follow-up visits, indicating they are taking buprenorphine and with urine toxicology positive for buprenorphine.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Days Illicit Opioids Used</measure>
      <time_frame>8 weeks</time_frame>
      <description>Number of Days Illicit Opioids Used, as indicated by participant self-report and urine toxicology results</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of Negative Urine Toxicologies</measure>
      <time_frame>weekly up to 8 weeks</time_frame>
      <description>Number of Negative Urine Toxicologies, as indicated by results from weekly urine toxicologies collected for eight weeks</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Quality of Life as assessed by the World Health Organization Quality of Life-BREF (WHOQOL-BREF)</measure>
      <time_frame>8 weeks</time_frame>
      <description>World Health Organization Quality of Life-BREF. The WHOQOL produces a multi-dimensional profile of scores across six domains and 24 sub-domains of quality of life, with higher scores representing a greater reported quality of life.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Depression as assessed by the Beck Depression Inventory II (BDII)</measure>
      <time_frame>8 weeks</time_frame>
      <description>The Beck Depression Inventory is a multi-item assessment for depression. Scores of 0-10 are considered within normal range, with higher scores representing worsening reported depression.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anxiety as assessed by the State-Trait Anxiety Inventory (STAI)</measure>
      <time_frame>8 weeks</time_frame>
      <description>The State-Trait Anxiety Inventory is a 40-item assessment of state and trait characteristics, with higher scores (more positive items) representing greater severity of mental states such as apprehension, tension, nervousness, and worry.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of Participants Abstinent from Other Drug Substances</measure>
      <time_frame>8 weeks</time_frame>
      <description>Abstinence from other substances will be measured by combining TLFB and urine toxicology results to report the number of participants who were abstinent from other drug substances</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Opioid Use Disorder</condition>
    <arm_group>
      <arm_group_label>High-dose psilocybin + buprenorphine</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>High-dose psilocybin (30 mg) session following standard-of-care buprenorphine induction</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Very low-dose psilocybin + buprenorphine</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Very low dose psilocybin session (1 mg) following standard-of-care buprenorphine induction</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Psilocybin</intervention_name>
      <description>The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis</description>
      <arm_group_label>High-dose psilocybin + buprenorphine</arm_group_label>
      <arm_group_label>Very low-dose psilocybin + buprenorphine</arm_group_label>
      <other_name>Buprenorphine</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age 21-70 years&#xD;
  &#xD;
            -  Have given written informed consent&#xD;
  &#xD;
            -  Meet diagnostic criteria for OUD&#xD;
  &#xD;
            -  No antidepressant medications for approximately 5 half-lives prior to enrollment&#xD;
  &#xD;
            -  Not currently taking methadone, buprenorphine or naltrexone&#xD;
  &#xD;
            -  Urine toxicology positive for an opioid&#xD;
  &#xD;
            -  Has access to stable housing&#xD;
  &#xD;
            -  Can read, write, and speak English fluently&#xD;
  &#xD;
            -  Be judged by study team clinicians to be at low risk for suicidality&#xD;
  &#xD;
            -  Have limited recent use of classic psychedelics (no use in the past year).&#xD;
  &#xD;
            -  Expresses a desire for sustained recovery from disordered opioid use.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          General medical exclusion criteria:&#xD;
  &#xD;
            -  Women who are pregnant, nursing, or not practicing an effective means of birth control&#xD;
  &#xD;
            -  Cardiovascular conditions: hypertension with resting blood pressure systolic &gt;139 or&#xD;
               diastolic &gt;89, angina, heart rate &gt; 99, a clinically significant electrocardiogram&#xD;
               abnormality (e.g., atrial fibrillation), Transient Ischemic Attack or Stroke in the&#xD;
               last 6 months, peripheral or pulmonary vascular disease, cardiac valvuopathy&#xD;
  &#xD;
            -  Epilepsy&#xD;
  &#xD;
            -  Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of&#xD;
               hypoglycemia&#xD;
  &#xD;
            -  Currently taking on a daily basis any medications (including herbal substances and&#xD;
               supplements) with a central nervous system effect on serotonin, including&#xD;
               serotonin-reuptake inhibitors and monoamine oxidase inhibitors.&#xD;
  &#xD;
               o For individuals who have intermittent or as needed use of such medications,&#xD;
               psilocybin sessions will not be conducted until at least 5 half-lives of the agent&#xD;
               have elapsed after the last dose.&#xD;
  &#xD;
            -  Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram&#xD;
               (Antabuse), Alcohol dehydrogenase inhibitors, or medicines such as phenytoin,&#xD;
               regorafenib, eltrombopag.&#xD;
  &#xD;
            -  Currently taking buprenorphine, methadone, or naltrexone.&#xD;
  &#xD;
            -  Unable or unwilling to discontinue acid-reducing agents or major metabolizing enzyme&#xD;
               inhibitors for 5-half lives prior to the experimental dosing session.&#xD;
  &#xD;
            -  Have a seizure disorder, multiple sclerosis, history of significant head trauma,&#xD;
               nervous system tumor, movement disorders or any neurodegenerative condition.&#xD;
  &#xD;
            -  Morbidly obese (&gt;100 pounds above ideal body weight, or Body Mass Index (BMI) &gt;=40, or&#xD;
               BMI &gt;=35 with high blood pressure or diabetes)&#xD;
  &#xD;
            -  Body weight &lt; 45 kilograms&#xD;
  &#xD;
            -  Be judged by a study team clinician to be at risk for moderate or severe alcohol or&#xD;
               benzodiazepine withdrawal.&#xD;
  &#xD;
            -  Allergic to buprenorphine or hydromorphone&#xD;
  &#xD;
            -  For blood samples, the following lab values will be exclusionary: transaminases&#xD;
               greater than x2 the upper limit of normal lab reference range, hemoglobin less than 11&#xD;
               g/d, and creatinine clearance &lt; 40 ml/min.&#xD;
  &#xD;
          Psychiatric Exclusion Criteria:&#xD;
  &#xD;
            -  Current or past history of meeting diagnostic criteria for Schizophrenia, Psychotic&#xD;
               Disorder (unless substance-induced or due to a medical condition), Bipolar I or II&#xD;
               Disorder or Major Depression with psychotic features.&#xD;
  &#xD;
            -  Have a first or second degree relative with schizophrenia, psychotic disorder (unless&#xD;
               substance induced or due to a medical condition), or bipolar I or II disorder.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>21 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Sandeep Nayak, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Johns Hopkins School of Medicine</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Andrew L Gaddis, MD</last_name>
      <phone>410-550-0048</phone>
      <email>gaddis@jhmi.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sandeep Nayak, MD</last_name>
      <phone>410-550-0048</phone>
      <email>smn@jhmi.edu</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Opioid-Related Disorders</mesh_term>
      <mesh_term>Substance-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>Psilocybin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06005662
  org study id: IRB00344281
  nct id: NCT06005662
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  This study will examine the effect of a single high dose of psilocybin therapy (30 mg) versus
        a very low dose (1 mg) as an adjunctive therapy to individuals undergoing standard-of-care
        buprenorphine treatment for Opioid use disorder (OUD). Effects of adjunctive psilocybin will
        be determined for longitudinal outcomes of opioid abstinence, compliance with buprenorphine
        maintenance, quality of life, and mood.
  The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose
        psilocybin (30 mg) session compared to a very low dose session (1 mg) following
        standard-of-care buprenorphine induction on drug abstinence, quality of life, craving,
        tobacco use, and treatment retention in healthy participants with an active OUD diagnosis.
        Use of buprenorphine follow standard of care, and the investigators are investigating the
        additive power of adjunctive psilocybin to enhance opioid abstinence, treatment adherence,
        quality of life, and mood.
  
        The study will consist of a brief (6-8 day) inpatient phase for standard buprenorphine
        induction as well as experimental psilocybin administration, an 8-week outpatient phase
        involving standard buprenorphine maintenance and experimental follow-up meetings, and
        long-term follow-up sessions for 4 months after. During the inpatient phase, participants
        will be inducted onto sublingual (SL) buprenorphine (using a buprenorphine/naloxone
        combination product) while admitted to the Bayview Clinical Research Unit. During this time,
        participants will also undergo 2-3 preparatory sessions, and will undergo an experimental
        drug administration session under supportive conditions, during which the participants will
        receive either a very low dose (1 mg) or a single high (30mg) oral dose of psilocybin under
        double-blind conditions. At the end of the inpatient phase, participants will be discharged
        to complete the 8-week outpatient phase, during which participants will undergo visits at 1,
        2, 3, 4, 6, and 8 weeks post-dosing session for monitoring of adverse events, clinical
        status, treatment adherence, and to receive a weekly supply of buprenorphine. All
        buprenorphine procedures will be open label and will follow standard-of-care practices.
  
        This trial utilizes a Bayesian sequential methodology, employing a maximum sample size of 90
        participants and calculating Bayes factors (starting at 20 participants and assessed after
        each 10) to assess evidence for the null and experimental hypotheses, enabling potential
        early stopping for efficacy or futility based on predetermined thresholds (Bayes factor of 6
        and 1/6). This will be calculated for the primary outcome of opioid abstinence at 8-weeks
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Participants and study team will be masked/blinded to intervention.
  measure: Opioid Abstinence
  time frame: up to 8 weeks
  description: Non-buprenorphine opioid abstinence as verified by urine toxicology at each visit and Timeline Follow Back (TLFB). These will be combined to assess opioid abstinence for each participant. These will be assessed at the 8-week timepoint for the previous 3-weeks. Missing values will be presumed positive.
  Timeline Follow Back (TLFB) for Opioids: This is a self-report of drug use per day. This procedure asks participants to retrospectively quantitate their use of drugs. Greater numbers indicate more days using a substance, smaller numbers or zeros mean less or no days using a substance
  Urine toxicology: Urine samples will be collected at each study visit and screened broadly for illicit drug use including opioids via an outside medical laboratory. Quantitative buprenorphine levels will also be collected following induction to gauge whether buprenorphine is being taken.
  These measurements will be combined to report the number of participants who were abstinent from opioids.
  measure: Treatment Retention
  time frame: 8 weeks
  description: Treatment retention at 8 weeks, as indicated by participants making all follow-up visits, indicating they are taking buprenorphine and with urine toxicology positive for buprenorphine.
  measure: Number of Days Illicit Opioids Used
  time frame: 8 weeks
  description: Number of Days Illicit Opioids Used, as indicated by participant self-report and urine toxicology results
  measure: Number of Negative Urine Toxicologies
  time frame: weekly up to 8 weeks
  description: Number of Negative Urine Toxicologies, as indicated by results from weekly urine toxicologies collected for eight weeks
  measure: Quality of Life as assessed by the World Health Organization Quality of Life-BREF (WHOQOL-BREF)
  time frame: 8 weeks
  description: World Health Organization Quality of Life-BREF. The WHOQOL produces a multi-dimensional profile of scores across six domains and 24 sub-domains of quality of life, with higher scores representing a greater reported quality of life.
  measure: Depression as assessed by the Beck Depression Inventory II (BDII)
  time frame: 8 weeks
  description: The Beck Depression Inventory is a multi-item assessment for depression. Scores of 0-10 are considered within normal range, with higher scores representing worsening reported depression.
  measure: Anxiety as assessed by the State-Trait Anxiety Inventory (STAI)
  time frame: 8 weeks
  description: The State-Trait Anxiety Inventory is a 40-item assessment of state and trait characteristics, with higher scores (more positive items) representing greater severity of mental states such as apprehension, tension, nervousness, and worry.
  measure: Number of Participants Abstinent from Other Drug Substances
  time frame: 8 weeks
  description: Abstinence from other substances will be measured by combining TLFB and urine toxicology results to report the number of participants who were abstinent from other drug substances
  arm group label: High-dose psilocybin + buprenorphine
  arm group type: Experimental
  description: High-dose psilocybin (30 mg) session following standard-of-care buprenorphine induction
  arm group label: Very low-dose psilocybin + buprenorphine
  arm group type: Active Comparator
  description: Very low dose psilocybin session (1 mg) following standard-of-care buprenorphine induction
  intervention type: Drug
  intervention name: Psilocybin
  description: The proposed study is a double-blind, controlled investigation of the effect of 1 high-dose psilocybin (30 mg) session compared to a very low dose session (1 mg) following standard-of-care buprenorphine induction on drug abstinence, quality of life, craving, tobacco use, and treatment retention in healthy participants with an active OUD diagnosis
  arm group label: High-dose psilocybin + buprenorphine
  arm group label: Very low-dose psilocybin + buprenorphine
  other name: Buprenorphine
  criteria: 
  gender: All
  minimum age: 21 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Sandeep Nayak, MD
  role: Principal Investigator
  affiliation: Johns Hopkins School of Medicine
  last name: Andrew L Gaddis, MD
  phone: 410-550-0048
  email: gaddis@jhmi.edu
  last name: Sandeep Nayak, MD
  phone: 410-550-0048
  email: smn@jhmi.edu
  responsible party type: Sponsor
  mesh term: Opioid-Related Disorders
  mesh term: Substance-Related Disorders
  mesh term: Buprenorphine
  mesh term: Psilocybin
  sharing ipd: No