<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/NCT04488601</url>
  </required_header>
  <id_info>
    <org_study_id>ALRx001</org_study_id>
    <nct_id>NCT04488601</nct_id>
  </id_info>
  <brief_title>Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study</brief_title>
  <acronym>PEARL</acronym>
  <official_title>Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study (PEARL): A Prospective, Double-Blind, Placebo-Controlled Trial for Rapamycin in Healthy Individuals Assessing Safety and Efficacy in Reducing Aging Effects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AgelessRx</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>AgelessRx</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 is a randomized, placebo-controlled trial into the safety and efficacy in reducing&#xD;
      clinical measures of aging in an older adult population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A randomized, double-blind, placebo-controlled trial assessing the effects of low and high&#xD;
      doses of intermittent Rapamycin on a weekly schedule. The researchers aim to establish a&#xD;
      long-term safety profile, determine the long-term efficacy of Rapamycin in reducing clinical&#xD;
      aging measures, and biochemical and physiological endpoints associated with declining health&#xD;
      and aging in healthy older adults.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 1, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Prospective, Double-Blind, Placebo-Controlled Trial</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in visceral fat as measured by dual-energy x-ray absorptiometry (DXA) scan</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Visceral fat changes from baseline as determined by DXA scan.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>bone density</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Changes in bone density from baseline as determined by DXA scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>lean body mass</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Changes in lean body mass from baseline as determined by DXA scan</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>adverse events</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Number of patients with adverse events using standard AE reporting (FDA regulations 21CFR314.80 and 1CFR213.32(s))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>complete blood count (CBC)</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>changes in CBC from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of blood electrolytes（serum potassium, sodium, chloride, and carbon dioxide in mmol/L）measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of blood electrolytes（serum potassium, sodium, chloride, and carbon dioxide in mmol/L) compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of liver function as measured by serum globulin in g/dL, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of liver function as measured by serum globulin in g/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of liver function as measured by serum bilirubin in mg/dL, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of liver function as measured by serum bilirubin in mg/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of liver function as measured by serum alkaline phosphatase, AST, and ALT in IU/L, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of liver function as measured by serum alkaline phosphatase, AST, and ALT in IU/L compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of renal function as measured by serum albumin in g/dL, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of renal function as measured by serum albumin in g/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of renal function as measured by serum creatinine and uric acid in mg/dL, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of renal function as measured by serum creatinine and uric acid in mg/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lipids (serum total cholesterol, triglycerides, HDL, and LDL cholesterol in mg/dL) measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of lipids（serum total cholesterol, triglycerides, HDL and LDL cholesterol in mg/dL) compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting serum glucose in mg/dL, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of fasting serum glucose in mg/dL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in insulin in uIU/mL, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of fasting serum insulin in uIU/mL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fasting serum IGF-1 in ng/mL, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of fasting serum IGF-1 in ng/mL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum Hemoglobin A1c in % of total hemoglobin, measured at baseline and after 6 and 12 months.</measure>
    <time_frame>6 month interim analysis of the data, 12 month safety profile will be established</time_frame>
    <description>Difference in the change of serum Hemoglobin A1c in % of total hemoglobin compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>Rapamycin 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rapamycin 5 mg/week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rapamycin 10</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rapamycin 10 mg/week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo 1</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo once per week</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rapamycin</intervention_name>
    <description>Rapamycin in 2 different dosage forms.</description>
    <arm_group_label>Rapamycin 10</arm_group_label>
    <arm_group_label>Rapamycin 5</arm_group_label>
    <other_name>Sirolimus</other_name>
    <other_name>Rapamune</other_name>
    <other_name>Rapacan</other_name>
    <other_name>Siromus</other_name>
    <other_name>Raparen</other_name>
    <other_name>Rapasim</other_name>
    <other_name>Sirova</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo capsules</description>
    <arm_group_label>Placebo 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 50-85&#xD;
&#xD;
          -  Any sex&#xD;
&#xD;
          -  Any ethnicity&#xD;
&#xD;
          -  Interest in taking Rapamycin off-label&#xD;
&#xD;
          -  Willing to undergo tests&#xD;
&#xD;
          -  Relatively good health with only well-managed chronic diseases (hypertension, coronary&#xD;
             artery disease, type II diabetes, etc.) clinically stable&#xD;
&#xD;
          -  Adequate cognitive function to be able to give informed consent&#xD;
&#xD;
          -  Technologically competent to complete web forms and perform video calls with the PI&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anemia - Hg &lt; 9.0 g/dl, Leukopenia - white blood cells (WBC) &lt; 3,500/mm3 , Neutropenia&#xD;
             - absolute neutrophil count &lt; 2,000/mm3 , or Platelet count - platelet count &lt;&#xD;
             125,000/mm3&#xD;
&#xD;
          -  Premenopausal females (due to menstruation-induced anemia, etc.)&#xD;
&#xD;
          -  Patients scheduled to undergo major surgery in the next 12 months&#xD;
&#xD;
          -  Patients undergoing or scheduled to undergo chemotherapy or any other treatment for&#xD;
             malignancy&#xD;
&#xD;
          -  Patients scheduled for immunosuppressant therapy for transplant&#xD;
&#xD;
          -  Patients with impaired wound healing or history of a chronic open wound&#xD;
&#xD;
          -  Untreated dyslipidemia with LDL-c &gt; 190 and family history of dyslipidemia, Total&#xD;
             cholesterol &gt; 350 mg/dl, or triglycerides &gt; 880 mg/dl.&#xD;
&#xD;
          -  Impaired hepatic function, including elevated alkaline Phosphatase levels, aspartate&#xD;
             aminotransferase (AST), alanine aminotransferase (ALT), Albumin, or T. Bili.&#xD;
&#xD;
          -  HIV/AIDS, chronic Lyme, Babesia, Ehrlichiosis, Anaplasmosis, or other chronic&#xD;
             infections that require ongoing treatment or monitoring&#xD;
&#xD;
          -  Allergy to Rapamycin&#xD;
&#xD;
          -  Any form of clinically relevant primary or secondary immune dysfunction or deficiency&#xD;
             (e.g. X-linked agammaglobulinemia (XLA), common variable immunodeficiency (CVID))&#xD;
&#xD;
          -  Chronic oral corticosteroid or immunosuppressive medication use (e.g. Enbrel, Humira,&#xD;
             methotrexate).&#xD;
&#xD;
          -  Fibromyalgia or Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Breast Implant&#xD;
             Illness,&#xD;
&#xD;
          -  Congestive heart failure: self-assessed functional status of heart failure New York&#xD;
             Heart Association (NYHA) classification III or IV&#xD;
&#xD;
          -  Impaired renal function, as defined as glomerular filtration rate (GFR) &lt; 30&#xD;
&#xD;
          -  Poorly controlled diabetes, as defined as HbA1c &gt; 7%&#xD;
&#xD;
          -  Type I Diabetes, or Insulin-dependent Type II diabetes&#xD;
&#xD;
          -  Substance abuse disorder either untreated or if treated within the last 5 years&#xD;
&#xD;
          -  PTSD, Bipolar disorder, Schizophrenia, or any other untreated or poorly controlled&#xD;
             mental health or mood disorder, or history of hospitalization due to mental health&#xD;
             condition&#xD;
&#xD;
          -  Those who have taken metformin, rapamycin, or rapalogs in the past 6 months&#xD;
&#xD;
               -  (volunteers who were on metformin for aging can participate, provided they agree&#xD;
                  to stop taking metformin before and during the trial)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James Watson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sajad Zalzala, MD</last_name>
    <role>Study Director</role>
    <affiliation>AgelessRx</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AgelessRx</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>October 3, 2022</last_update_submitted>
  <last_update_submitted_qc>October 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>rapamycin</keyword>
  <keyword>aging</keyword>
  <keyword>longevity</keyword>
  <keyword>sirolimus</keyword>
  <keyword>healthy aging</keyword>
  <keyword>age-related conditions</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>as soon as available</ipd_time_frame>
    <ipd_access_criteria>Institutional review board (IRB) approval or at the discretion of PI/sponsor</ipd_access_criteria>
  </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/NCT04488601
org study id: ALRx001
nct id: NCT04488601
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a randomized, placebo-controlled trial into the safety and efficacy in reducing
      clinical measures of aging in an older adult population.
A randomized, double-blind, placebo-controlled trial assessing the effects of low and high
      doses of intermittent Rapamycin on a weekly schedule. The researchers aim to establish a
      long-term safety profile, determine the long-term efficacy of Rapamycin in reducing clinical
      aging measures, and biochemical and physiological endpoints associated with declining health
      and aging in healthy older adults.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, Double-Blind, Placebo-Controlled Trial
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in visceral fat as measured by dual-energy x-ray absorptiometry (DXA) scan
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Visceral fat changes from baseline as determined by DXA scan.
measure: bone density
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Changes in bone density from baseline as determined by DXA scan
measure: lean body mass
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Changes in lean body mass from baseline as determined by DXA scan
measure: adverse events
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Number of patients with adverse events using standard AE reporting (FDA regulations 21CFR314.80 and 1CFR213.32(s))
measure: complete blood count (CBC)
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: changes in CBC from baseline
measure: Change of blood electrolytes（serum potassium, sodium, chloride, and carbon dioxide in mmol/L）measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of blood electrolytes（serum potassium, sodium, chloride, and carbon dioxide in mmol/L) compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change of liver function as measured by serum globulin in g/dL, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of liver function as measured by serum globulin in g/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change of liver function as measured by serum bilirubin in mg/dL, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of liver function as measured by serum bilirubin in mg/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change of liver function as measured by serum alkaline phosphatase, AST, and ALT in IU/L, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of liver function as measured by serum alkaline phosphatase, AST, and ALT in IU/L compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change of renal function as measured by serum albumin in g/dL, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of renal function as measured by serum albumin in g/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change of renal function as measured by serum creatinine and uric acid in mg/dL, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of renal function as measured by serum creatinine and uric acid in mg/dL compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change in lipids (serum total cholesterol, triglycerides, HDL, and LDL cholesterol in mg/dL) measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of lipids（serum total cholesterol, triglycerides, HDL and LDL cholesterol in mg/dL) compared with the baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change in fasting serum glucose in mg/dL, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of fasting serum glucose in mg/dL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change in insulin in uIU/mL, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of fasting serum insulin in uIU/mL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change in fasting serum IGF-1 in ng/mL, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of fasting serum IGF-1 in ng/mL compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.
measure: Change in serum Hemoglobin A1c in % of total hemoglobin, measured at baseline and after 6 and 12 months.
time frame: 6 month interim analysis of the data, 12 month safety profile will be established
description: Difference in the change of serum Hemoglobin A1c in % of total hemoglobin compared with baseline at 6 and 12 months between the intervention and control group is to be analyzed.
arm group label: Rapamycin 5
arm group type: Experimental
description: Rapamycin 5 mg/week
arm group label: Rapamycin 10
arm group type: Experimental
description: Rapamycin 10 mg/week
arm group label: Placebo 1
arm group type: Placebo Comparator
description: Placebo once per week
intervention type: Drug
intervention name: Rapamycin
description: Rapamycin in 2 different dosage forms.
arm group label: Rapamycin 10
arm group label: Rapamycin 5
other name: Sirolimus
other name: Rapamune
other name: Rapacan
other name: Siromus
other name: Raparen
other name: Rapasim
other name: Sirova
intervention type: Drug
intervention name: Placebo
description: Placebo capsules
arm group label: Placebo 1
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: James Watson, MD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Sajad Zalzala, MD
role: Study Director
affiliation: AgelessRx
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sirolimus
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: as soon as available
ipd access criteria: Institutional review board (IRB) approval or at the discretion of PI/sponsor