<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/NCT04421105</url>
  </required_header>
  <id_info>
    <org_study_id>CAS-50-37-3-01</org_study_id>
    <nct_id>NCT04421105</nct_id>
  </id_info>
  <brief_title>A Double-blind, Placebo-controlled Study to Evaluate Very Low Dose LSD in Healthy Volunteers Aged 55-75 Years</brief_title>
  <official_title>A Phase 1,Single-centre, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Very Low Dose LSD (5 µg, 10 µg, 20 µg) in Healthy Volunteers Aged 55-75 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eleusis Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eleusis Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study was a Phase 1, double-blind, placebo-controlled, randomised study of very low dose&#xD;
      LSD. Healthy volunteers aged 55 to 75 years with no use of LSD in the past 5 years were&#xD;
      screened within 28 days of randomization. Subjects who met all inclusion and no exclusion&#xD;
      criteria and provided written informed consent were randomised a 1:1:1:1 ratio to receive 6&#xD;
      doses of 5 µg, 10 µg, or 20 µg LSD or placebo, at 4-day intervals for 21 days (on Study Days&#xD;
      1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the&#xD;
      last dose of LSD. A total of 48 subjects were enrolled.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The magnitude of the effect of LSD was explored across specific PD measures.&#xD;
&#xD;
      These included:&#xD;
&#xD;
        -  Cognition and affect, including evaluation of memory, temporal perception, executive&#xD;
           function, and learning&#xD;
&#xD;
        -  Subjective effects&#xD;
&#xD;
        -  Proprioception and balance&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 29, 2015</start_date>
  <completion_date type="Actual">November 5, 2015</completion_date>
  <primary_completion_date type="Actual">October 30, 2015</primary_completion_date>
  <phase>Phase 1</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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the safety and tolerability of very low dose LSD</measure>
    <time_frame>2.5 weeks</time_frame>
    <description>Assessment of Adverse Events by % frequency</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To evaluate the pharmacokinetics of very low dose LSD - Variation of plasma concentration over time</measure>
    <time_frame>12 hours</time_frame>
    <description>AUC 0-12h ( pg/mL*h): area under the plasma concentration-time curve profiles from time zero to the 12 hour sample determined using the linear trapezoidal rule.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To evaluate the pharmacokinetics of very low dose LSD - Maximum Peak concentration of drug</measure>
    <time_frame>12 hours</time_frame>
    <description>Cmax (pg/mL): maximum drug plasma concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To evaluate the pharmacokinetics of very low dose LSD - Half life of drug</measure>
    <time_frame>12 hours</time_frame>
    <description>Tmax (h): time to reach maximum plasma concentration Tlag (h): time for drug to appear in plasma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on cognition.</measure>
    <time_frame>2.5 weeks</time_frame>
    <description>The CANTAB (Cambridge Neuropsychological Test Automated Battery ) included four test that measured cognitive function. These were Reaction Time (RTI) for reaction times, Paired Associates Learning (PAL) for visual memory and learning, Rapid Visual Information Processing (RVP) for sustained memory, Spatial Working Memory (SWM) for retention of visuospatial information.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on Acute subjective effects.</measure>
    <time_frame>2.5 weeks</time_frame>
    <description>Assessed by the Visual Analog Scale (VAS). Items assess acute subjective drug effects (e.g. intensity, liking) Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on the characteristics of altered states of consciousness assessed by questionnaire</measure>
    <time_frame>2.5 weeks</time_frame>
    <description>5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The scale ranges from no, not more than usual (on the left) to yes, very much more than usual (on the right). Items retrospectively assess subjective drug effects. Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects associated with a different state of consciousness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on Balance tracking</measure>
    <time_frame>2.5 weeks</time_frame>
    <description>Static balance as assessed by center of pressure (COP) using a portable force plate (Balance Tracking Systems, BTrackS™)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on Proprioception</measure>
    <time_frame>2.5 weeks</time_frame>
    <description>The ability to sense stimuli arising within the body regarding position and motion will be measured in 15 trials during which the participant will have their arm rotated to set angles and asked to reproduce the angle while blindfolded. Performance is measured as the absolute error between the target and matching angle.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Exploratory Objective To evaluate the pharmacokinetic (PK)/PD relationship between very low dose LSD concentration and cognitive changes.</measure>
    <time_frame>2.5 weeks</time_frame>
    <description>The relationship between LSD plasma concentration, selected PK parameters and cumulative effects of repeated LSD administration was evaluated using correlation and/or linear regression methods to evaluate possible associations with changes in cognition or affect.</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Group 1 N=12</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 doses at 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 N=12</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 doses at 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3 N=12</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 doses at 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4 N=12</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>6 doses 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lysergic acid diethylamide (LSD) 5µg</intervention_name>
    <arm_group_label>Group 1 N=12</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lysergic acid diethylamide (LSD) 10µg</intervention_name>
    <arm_group_label>Group 2 N=12</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lysergic acid diethylamide (LSD)20 µg</intervention_name>
    <arm_group_label>Group 3 N=12</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Group 4 N=12</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Healthy male or female subjects aged 55 to 75 years, inclusive (site staff&#xD;
             endeavoured to achieve a median age of 65 years across all subjects).&#xD;
&#xD;
             2. Subject has not been previously exposed to LSD within the past 5 years. 3. Subject&#xD;
             is able and willing to give written informed consent, adhere to the compliance terms&#xD;
             during participation in the study, undergo the examinations and testing set forth in&#xD;
             the study protocol, and clearly and reliably communicate their subjective symptoms to&#xD;
             the Investigator.&#xD;
&#xD;
             4. A female subject is eligible to participate if she is postmenopausal (has&#xD;
             experienced 12 consecutive months without menstruation).&#xD;
&#xD;
             5. A male subject with a female partner is eligible to participate if he agrees to use&#xD;
             a double barrier method of contraception. This criterion must be followed from the&#xD;
             time of the first dose of study medication until 3 months post-last dose. Male&#xD;
             subjects must not donate sperm for 3 months following the last dose of study&#xD;
             medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  General Health&#xD;
&#xD;
               1. Subject has a history or evidence of clinically relevant psychiatric,&#xD;
                  respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic,&#xD;
                  neurological, cardiovascular, musculoskeletal, genitourinary, immunological,&#xD;
                  dermatological, connective tissue diseases or disorders, as judged by the&#xD;
                  investigator.&#xD;
&#xD;
               2. Subject has resting BP exceeding 160 mmHg (systolic) and 90 mmHg (diastolic),&#xD;
                  averaged across 4 assessments taken on the same day. BP measurements were taken&#xD;
                  at least 1 min apart&#xD;
&#xD;
               3. Subject has a presence or relevant history of organic brain disorders (e.g.&#xD;
                  intracranial hypertension, impaired consciousness, lethargy, and brain tumour).&#xD;
&#xD;
               4. Subject has a relevant history of atopy, hypersensitivity, skin allergies or&#xD;
                  allergic reactions to drugs.&#xD;
&#xD;
               5. Subject has a clinical laboratory test result outside the reference ranges of the&#xD;
                  testing laboratory and considered clinically significant by the investigator.&#xD;
&#xD;
               6. Subject is positive for hepatitis B surface antigen (HBsAg), hepatitis C virus&#xD;
                  (HCV) antibody or human immunodeficiency virus I and II at screening.&#xD;
&#xD;
               7. Subject is a current smoker. (Has not smoked for at least 1 month prior to the&#xD;
                  screening visit).&#xD;
&#xD;
               8. Subject has a history of drug abuse/dependence in the last 12 months or has a&#xD;
                  current drug abuse/dependence, and/or is positive for drugs of abuse and alcohol&#xD;
                  tests at screening and/or baseline.&#xD;
&#xD;
               9. Subject has a medical history that would affect the subject's safety or the study&#xD;
                  endpoints.&#xD;
&#xD;
              10. Subject has used prescription drugs or therapy within 7 days of first dosing,&#xD;
                  unless agreed as non clinically relevant by the investigator and the Medical&#xD;
                  Monitor.&#xD;
&#xD;
              11. Subject has used over the counter (OTC) medication or therapy, including&#xD;
                  mega-dose vitamin therapy (but excluding routine vitamins) within 7 days of first&#xD;
                  dosing, unless agreed as non clinically relevant by the investigator and the&#xD;
                  Medical Monitor.&#xD;
&#xD;
              12. Subject has donated or received any blood or blood products within the previous 3&#xD;
                  months prior to first dosing.&#xD;
&#xD;
              13. Subject cannot use a computer at the required minimum level.&#xD;
&#xD;
              14. Subject has used any investigational drug or participated in any clinical trial&#xD;
                  within 3 months of their first dosing.&#xD;
&#xD;
              15. Subject has a current sleep disorder.&#xD;
&#xD;
              16. Subject has a history of cataracts, active glaucoma or any other ophthalmic&#xD;
                  condition that could interfere with the eye blink assessment.&#xD;
&#xD;
              17. Subject has a hearing loss of more than 40 dB. Subjects with &gt; 40dB hearing loss&#xD;
                  at less than 1500Hz were excluded Subjects with &gt; 40dB hearing loss at 1500Hz or&#xD;
                  higher can be included in the study. The hearing result from the ear with the&#xD;
                  best hearing. Provided one ear can hear at the above levels then the patient can&#xD;
                  be included.&#xD;
&#xD;
              18. Subject has veins unsuitable for venipuncture and/or cannulation.&#xD;
&#xD;
              19. Subject has a corrected QT interval using Fridericia's correction &gt;450&#xD;
                  milliseconds at any single reading.&#xD;
&#xD;
              20. Subject is unlikely to co-operate with the requirements of the study, in the&#xD;
                  opinion of the Principal Investigator (PI) or designee.&#xD;
&#xD;
        B. Psychiatric health&#xD;
&#xD;
          1. Based on the modified SCID-CT, a subject with the lifetime presence of any of the&#xD;
             following is excluded: psychotic symptoms that are not substance-induced or due to a&#xD;
             medical condition or has a first- or second-degree relative with these disorders; any&#xD;
             manic or hypomanic episode; lifetime presence of any major depressive episode;&#xD;
             lifetime presence of substance abuse, or dependence on any substance in the past 5&#xD;
             years; current diagnosis of obsessive-compulsive disorder (OCD), dysthymic disorder,&#xD;
             panic disorder, anorexia, and bulimia.&#xD;
&#xD;
          2. Subject is receiving chronic administration of tricyclic antidepressants or lithium or&#xD;
             acute administration of selective serotonin reuptake inhibitors (SSRIs) or&#xD;
             haloperidol, or serotonin-norepinephrine reuptake inhibitors (SNRIs) or monoamine&#xD;
             oxidase inhibitors.&#xD;
&#xD;
          3. Subject is taking OTC doses of 5-HT or St John's Wort or Ayahuasca (which contains&#xD;
             monoamine oxidase inhibitors in addition to dimethyltryptamine [DMT]).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Research and Development Director</last_name>
    <role>Study Director</role>
    <affiliation>Eleusis Therapeutics</affiliation>
  </overall_official>
  <link>
    <url>http://link.springer.com/article/10.1007/s00213-019-05417-7</url>
    <description>Study publication</description>
  </link>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 7, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 4, 2020</last_update_submitted>
  <last_update_submitted_qc>June 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lysergic Acid Diethylamide</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/NCT04421105
org study id: CAS-50-37-3-01
nct id: NCT04421105
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study was a Phase 1, double-blind, placebo-controlled, randomised study of very low dose
      LSD. Healthy volunteers aged 55 to 75 years with no use of LSD in the past 5 years were
      screened within 28 days of randomization. Subjects who met all inclusion and no exclusion
      criteria and provided written informed consent were randomised a 1:1:1:1 ratio to receive 6
      doses of 5 µg, 10 µg, or 20 µg LSD or placebo, at 4-day intervals for 21 days (on Study Days
      1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the
      last dose of LSD. A total of 48 subjects were enrolled.
The magnitude of the effect of LSD was explored across specific PD measures.

      These included:

        -  Cognition and affect, including evaluation of memory, temporal perception, executive
           function, and learning

        -  Subjective effects

        -  Proprioception and balance
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: To evaluate the safety and tolerability of very low dose LSD
time frame: 2.5 weeks
description: Assessment of Adverse Events by % frequency
measure: To evaluate the pharmacokinetics of very low dose LSD - Variation of plasma concentration over time
time frame: 12 hours
description: AUC 0-12h ( pg/mL*h): area under the plasma concentration-time curve profiles from time zero to the 12 hour sample determined using the linear trapezoidal rule.
measure: To evaluate the pharmacokinetics of very low dose LSD - Maximum Peak concentration of drug
time frame: 12 hours
description: Cmax (pg/mL): maximum drug plasma concentration
measure: To evaluate the pharmacokinetics of very low dose LSD - Half life of drug
time frame: 12 hours
description: Tmax (h): time to reach maximum plasma concentration Tlag (h): time for drug to appear in plasma
measure: To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on cognition.
time frame: 2.5 weeks
description: The CANTAB (Cambridge Neuropsychological Test Automated Battery ) included four test that measured cognitive function. These were Reaction Time (RTI) for reaction times, Paired Associates Learning (PAL) for visual memory and learning, Rapid Visual Information Processing (RVP) for sustained memory, Spatial Working Memory (SWM) for retention of visuospatial information.
measure: To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on Acute subjective effects.
time frame: 2.5 weeks
description: Assessed by the Visual Analog Scale (VAS). Items assess acute subjective drug effects (e.g. intensity, liking) Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects
measure: To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on the characteristics of altered states of consciousness assessed by questionnaire
time frame: 2.5 weeks
description: 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The scale ranges from no, not more than usual (on the left) to yes, very much more than usual (on the right). Items retrospectively assess subjective drug effects. Item scores are assessed on a visual scale ranging from 1% to 100%. Higher scores indicate greater subjective effects associated with a different state of consciousness
measure: To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on Balance tracking
time frame: 2.5 weeks
description: Static balance as assessed by center of pressure (COP) using a portable force plate (Balance Tracking Systems, BTrackS™)
measure: To evaluate the pharmacodynamic (PD) and cumulative effect of very low dose LSD on Proprioception
time frame: 2.5 weeks
description: The ability to sense stimuli arising within the body regarding position and motion will be measured in 15 trials during which the participant will have their arm rotated to set angles and asked to reproduce the angle while blindfolded. Performance is measured as the absolute error between the target and matching angle.
measure: Exploratory Objective To evaluate the pharmacokinetic (PK)/PD relationship between very low dose LSD concentration and cognitive changes.
time frame: 2.5 weeks
description: The relationship between LSD plasma concentration, selected PK parameters and cumulative effects of repeated LSD administration was evaluated using correlation and/or linear regression methods to evaluate possible associations with changes in cognition or affect.
arm group label: Group 1 N=12
arm group type: Experimental
description: 6 doses at 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.
arm group label: Group 2 N=12
arm group type: Experimental
description: 6 doses at 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.
arm group label: Group 3 N=12
arm group type: Experimental
description: 6 doses at 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.
arm group label: Group 4 N=12
arm group type: Placebo Comparator
description: 6 doses 4-day intervals for 21 days (on Study Days 1, 5, 9, 13, 17, and 21). A follow-up visit was conducted approximately 4 weeks after the last dose.
intervention type: Drug
intervention name: Lysergic acid diethylamide (LSD) 5µg
arm group label: Group 1 N=12
intervention type: Drug
intervention name: Lysergic acid diethylamide (LSD) 10µg
arm group label: Group 2 N=12
intervention type: Drug
intervention name: Lysergic acid diethylamide (LSD)20 µg
arm group label: Group 3 N=12
intervention type: Drug
intervention name: Placebo
arm group label: Group 4 N=12
criteria: 
gender: All
minimum age: 55 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Research and Development Director
role: Study Director
affiliation: Eleusis Therapeutics
url: http://link.springer.com/article/10.1007/s00213-019-05417-7
description: Study publication
responsible party type: Sponsor
mesh term: Lysergic Acid Diethylamide
sharing ipd: No