<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/NCT02981329</url>
  </required_header>
  <id_info>
    <org_study_id>H-38457 Metformin</org_study_id>
    <nct_id>NCT02981329</nct_id>
  </id_info>
  <brief_title>Fetal Hemoglobin Induction Treatment Metformin</brief_title>
  <acronym>FITMet</acronym>
  <official_title>Use of Metformin as a Fetal Hemoglobin Inducer in Patients With Hemoglobinopathies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Baylor College of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether metformin is effective in the treatment for&#xD;
      sickle cell anemia (SCA).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a dose escalation, pilot study for subjects with sickle cell anemia (SCA) disease to&#xD;
      determine if metformin has a beneficial effect on the treatment and quality of life of SCA&#xD;
      patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2, 2017</start_date>
  <completion_date type="Actual">July 20, 2020</completion_date>
  <primary_completion_date type="Actual">July 20, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Fetal Hemoglobin (HbF) Percentage (SCA) or Change in Total Hemoglobin (Hb)</measure>
    <time_frame>1 Year</time_frame>
    <description>Change in HbF percentage (%) or total Hb will be assessed by comparing baseline values to on treatment values per subject and will be summarized.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Laboratory Values</measure>
    <time_frame>1 Year</time_frame>
    <description>Evaluation and percentage of change in numeric values of total blood count, liver function, HbF levels, whole blood viscosity, and percent dense red blood cells will be evaluated per subject over the duration of the study and summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact on Quality of Life</measure>
    <time_frame>1 Year</time_frame>
    <description>Evaluation of subject's change in quality of life will be assessed per subject per study questionnaire(s) over the duration of the study and summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Variability of Hemoglobin Response</measure>
    <time_frame>1 Year</time_frame>
    <description>Evaluation of hematological variability of fetal hemoglobin induction will be assessed per subject per genetic analysis and summarized.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of RNA Sequencing</measure>
    <time_frame>1 Year</time_frame>
    <description>Evaluate expression changes in paired samples collected before and on metformin through RNA sequencing.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Sickle Cell Anemia</condition>
  <condition>Sickle Cell Disease</condition>
  <condition>Hemoglobin Disorder</condition>
  <arm_group>
    <arm_group_label>Group A: Hydroxyurea + Metformin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who are currently taking Hydroxyurea as part of standard of care and have sickle cell anemia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: Metformin (Group B has closed to enrollment)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects who are not taking Hydroxyurea as part of standard of care and have sickle cell anemia.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metfomin will be taken daily. The metformin dose will be increased during two time points per subject if protocol dose escalation criteria is met.</description>
    <arm_group_label>Group A: Hydroxyurea + Metformin</arm_group_label>
    <arm_group_label>Group B: Metformin (Group B has closed to enrollment)</arm_group_label>
    <other_name>Glucophage</other_name>
    <other_name>Riomet,</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <description>Questionnaires will be completed to assess the impact quality of life</description>
    <arm_group_label>Group A: Hydroxyurea + Metformin</arm_group_label>
    <arm_group_label>Group B: Metformin (Group B has closed to enrollment)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Confirmed diagnosis of sickle cell anemia&#xD;
&#xD;
          2. Age greater than or equal to 10 and less than or equal to 60 years of age.&#xD;
&#xD;
          3. If on hydroxyurea, fetal hemoglobin less than 20% at a stable dose (mg/kg) determined&#xD;
             by the primary hematology provider over at least four months.&#xD;
&#xD;
          4. Creatinine less than or equal to 1.4 mg/dL and estimated glomerular filtration rate&#xD;
             greater than 45 ml/min/1.73 m2&#xD;
&#xD;
          5. Liver function tests (specifically ALT and conjugated bilirubin) less than or equal to&#xD;
             4 times upper limits of normal.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Failure to meet inclusion criteria&#xD;
&#xD;
          2. Simple or chronic red blood cell transfusion therapy in the last 3 months OR a HbA&#xD;
             level greater than 5% in SCA patients&#xD;
&#xD;
          3. Refusal to use medically effective birth control if female and sexually active.&#xD;
&#xD;
          4. If on hydroxyurea, not at stable dose of hydroxyurea for a minimum of 4 months&#xD;
             (temporary exclusion).&#xD;
&#xD;
          5. Creatinine greater than 1.4mg/dL&#xD;
&#xD;
          6. Liver function tests (ALT and conjugated bilirubin) greater than 4 times upper limits&#xD;
             of normal.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Titilope Fasipe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center at Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 2, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>February 20, 2023</last_update_submitted>
  <last_update_submitted_qc>February 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Baylor College of Medicine</investigator_affiliation>
    <investigator_full_name>Titilope Fasipe</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Metformin</keyword>
  <keyword>Sickle Cell Anemia</keyword>
  <keyword>Sickle Cell Disease</keyword>
  <keyword>Hemoglobinopathies</keyword>
  <keyword>Hemoglobin Disorder</keyword>
  <keyword>Blood Disease</keyword>
  <keyword>Hemoglobin Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anemia, Sickle Cell</mesh_term>
    <mesh_term>Hemoglobinopathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The leftover blood samples for genetic analysis will be banked indefinitely for future ancillary studies. Investigator who desires access to these samples must present their research idea prior to receiving access to the samples. The samples will be shared with researchers affiliated with Texas Children's Hospital, Baylor College of Medicine and/or other hematology collaborators for future studies associated with hematologic diseases and drugs used to treat such diseases. The recipient investigators are required to provide proof of IRB approval or exemption as per local IRB guidelines before the sample can be released for research purposes. After receipt of IRB approval, coded samples will be distributed to the recipient investigator.</ipd_description>
  </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/NCT02981329
org study id: H-38457 Metformin
nct id: NCT02981329
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine whether metformin is effective in the treatment for
      sickle cell anemia (SCA).
This is a dose escalation, pilot study for subjects with sickle cell anemia (SCA) disease to
      determine if metformin has a beneficial effect on the treatment and quality of life of SCA
      patients.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Fetal Hemoglobin (HbF) Percentage (SCA) or Change in Total Hemoglobin (Hb)
time frame: 1 Year
description: Change in HbF percentage (%) or total Hb will be assessed by comparing baseline values to on treatment values per subject and will be summarized.
measure: Change in Laboratory Values
time frame: 1 Year
description: Evaluation and percentage of change in numeric values of total blood count, liver function, HbF levels, whole blood viscosity, and percent dense red blood cells will be evaluated per subject over the duration of the study and summarized.
measure: Impact on Quality of Life
time frame: 1 Year
description: Evaluation of subject's change in quality of life will be assessed per subject per study questionnaire(s) over the duration of the study and summarized.
measure: Variability of Hemoglobin Response
time frame: 1 Year
description: Evaluation of hematological variability of fetal hemoglobin induction will be assessed per subject per genetic analysis and summarized.
measure: Evaluation of RNA Sequencing
time frame: 1 Year
description: Evaluate expression changes in paired samples collected before and on metformin through RNA sequencing.
arm group label: Group A: Hydroxyurea + Metformin
arm group type: Experimental
description: Subjects who are currently taking Hydroxyurea as part of standard of care and have sickle cell anemia.
arm group label: Group B: Metformin (Group B has closed to enrollment)
arm group type: Experimental
description: Subjects who are not taking Hydroxyurea as part of standard of care and have sickle cell anemia.
intervention type: Drug
intervention name: Metformin
description: Metfomin will be taken daily. The metformin dose will be increased during two time points per subject if protocol dose escalation criteria is met.
arm group label: Group A: Hydroxyurea + Metformin
arm group label: Group B: Metformin (Group B has closed to enrollment)
other name: Glucophage
other name: Riomet,
intervention type: Behavioral
intervention name: Questionnaires
description: Questionnaires will be completed to assess the impact quality of life
arm group label: Group A: Hydroxyurea + Metformin
arm group label: Group B: Metformin (Group B has closed to enrollment)
criteria: 
gender: All
minimum age: 10 Years
maximum age: 60 Years
healthy volunteers: No
last name: Titilope Fasipe, MD
role: Principal Investigator
affiliation: Baylor College of Medicine
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Baylor College of Medicine
investigator full name: Titilope Fasipe
investigator title: Assistant Professor
mesh term: Anemia, Sickle Cell
mesh term: Hemoglobinopathies
mesh term: Metformin
sharing ipd: Yes
ipd description: The leftover blood samples for genetic analysis will be banked indefinitely for future ancillary studies. Investigator who desires access to these samples must present their research idea prior to receiving access to the samples. The samples will be shared with researchers affiliated with Texas Children's Hospital, Baylor College of Medicine and/or other hematology collaborators for future studies associated with hematologic diseases and drugs used to treat such diseases. The recipient investigators are required to provide proof of IRB approval or exemption as per local IRB guidelines before the sample can be released for research purposes. After receipt of IRB approval, coded samples will be distributed to the recipient investigator.