<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/NCT01683825</url>
  </required_header>
  <id_info>
    <org_study_id>2012P001322</org_study_id>
    <nct_id>NCT01683825</nct_id>
  </id_info>
  <brief_title>Imaging Cardiac Amyloidosis: A Pilot Study Using F-18 Florbetapir Positron Emission Tomography</brief_title>
  <official_title>Imaging Cardiac Amyloidosis: A Pilot Study Using F-18 Florbetapir Positron Emission Tomography</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim of this pilot study is to determine whether amyloid deposits in the heart can&#xD;
      be measured non-invasively by F-18 florbetapir (Trade Name: Amyvid) positron emission&#xD;
      tomography (PET) in 30 individuals with documented cardiac amyloidosis. We will also enroll&#xD;
      15 individuals without cardiac amyloidosis to undergo the F-18 florbetapir imaging as a&#xD;
      control group.&#xD;
&#xD;
      The primary hypothesis of this study is that a specific amyloid binding radiotracer will bind&#xD;
      to the myocardial amyloid deposits and help quantify cardiac amyloid burden.&#xD;
&#xD;
      A secondary aim of this study is to determine reproducibility of F-18 florbetapir imaging of&#xD;
      the myocardium.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      F-18 florbetapir has been studied in multiple clinical trials to image beta-amyloid&#xD;
      deposition in the brain of subjects with Alzheimers' disease. Florbetapir F-18 has been well&#xD;
      tolerated in studies of more than 2000 human subjects. Biodistribution studies in humans&#xD;
      revealed predominantly hepatobiliary excretion. The tracer clears rapidly from the blood pool&#xD;
      in about 20 minutes. This radiotracer has been recently approved for clinical imaging of&#xD;
      brain amyloid in subjects with suspected Alzheimers disease. The investigators propose to&#xD;
      test this FDA approved radiotracer for an off label indication in a pilot study to evaluate&#xD;
      its potential utility, if any, to image cardiac amyloidosis.&#xD;
&#xD;
      Amyloid related heart disease is associated with LV wall thickening due to infiltration;&#xD;
      however, this myocardial wall thickening is not definitively distinguishable from left&#xD;
      ventricular myocyte hypertrophy from increased afterload to the heart from hypertension or&#xD;
      aortic stenosis. Typically myocardial or other tissue biopsy with typical echo features of&#xD;
      amyloidosis is required for confirmation of amyloidosis. This pilot study is designed to&#xD;
      understand whether cardiac amyloid burden can be measured using a specific radiotracer&#xD;
      targeted against amyloid protein (F-18 Florbetapir). At this point it is unknown of F-18&#xD;
      Florbetapir will bind to either AL or TTR amyloid protein or to both of them or to neither of&#xD;
      them. The investigators would like to study 15 patients with AL and 15 patients with TTR&#xD;
      amyloidosis to understand these differences if any. The investigators also seek to understand&#xD;
      if the signal to noise ratio of the circulating amyloid protein in the blood pool (AL amyloid&#xD;
      disease) allows for good differentiation of myocardial amyloid uptake. 15 individuals without&#xD;
      cardiac amyloidosis will also be enrolled as controls for this study.&#xD;
&#xD;
      The purpose of the proposed research study is to examine in detail, using quantitative PET,&#xD;
      myocardial F-18 Florbetapir uptake in cardiac amyloidosis in order to better understand&#xD;
      mechanisms of heart damage in this disease. A secondary aim of this study is to determine&#xD;
      reproducibility of F-18 florbetapir imaging of the myocardium in a subset of patients with&#xD;
      amyloidosis who return for a second F-18 florbetapir scan within 30 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow recruitment into the study due to competing study protocols&#xD;
  </why_stopped>
  <start_date type="Actual">March 23, 2013</start_date>
  <completion_date type="Actual">October 4, 2018</completion_date>
  <primary_completion_date type="Actual">January 3, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean</measure>
    <time_frame>1 day</time_frame>
    <description>Standardized uptake value (SUV) mean is defined as the mean F-18 florbetapir activity concentration [kBq/ml] measured within the left ventricular myocardial region of interest multiplied by the decay-corrected amount of injected F-18 florbetapir [kBq] normalized to patient weight [g]. In this study we will measure mean left ventricular global myocardial F-18 Florbetapir SUVmean on static images between 4 minutes to 30 minutes post injection of F-18 florbetapir.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Global Left Ventricular F-18 Florbetapir SUVmean From Scan 1 to Scan 2</measure>
    <time_frame>Repeat scan was performed a median of 7 days after baseline study (range 1-46 days)</time_frame>
    <description>We evaluated change in F-18 florbetapir SUVmean from scan 1 to scan 2 as a percentage value [(SUVmean1 minus SUVmean 2)/(SUVmean 1)*100]. In the 7 participants with cardiac amyloidosis who underwent two studies (median of 7 days apart), the percentage change in F-18 florbetapir SUVmean from scan 1 to scan 2 ranged from -38.5% to +20.8% with a median value of +2.24%.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Cardiac Amyloidosis</condition>
  <arm_group>
    <arm_group_label>F-18 florbetapir PET-Amyloid Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F-18 florbetapir PET-Healthy Controls</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individuals without documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>F-18 florbetapir PET-Amyloid Reproducibility Subjects</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Some of the individuals with documented cardiac amyloidosis from arm 1 will undergo a second F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET) within 30 days to measure reproducibility</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>F-18 florbetapir PET</intervention_name>
    <description>Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
    <arm_group_label>F-18 florbetapir PET-Amyloid Reproducibility Subjects</arm_group_label>
    <arm_group_label>F-18 florbetapir PET-Amyloid Subjects</arm_group_label>
    <arm_group_label>F-18 florbetapir PET-Healthy Controls</arm_group_label>
    <other_name>F-18 labeled Florbetapir (Trade Name: Amyvid)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria for amyloid subjects:&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Biopsy proven amyloidosis outside the heart with typical echocardiographic appearance&#xD;
             of cardiac involvement, or a positive cardiac biopsy.&#xD;
&#xD;
          -  Diagnosis of AL amyloidosis by standard criteria (evidence of plasma cell dyscrasia&#xD;
             with appropriate tissue staining for AL) OR&#xD;
&#xD;
          -  Diagnosis of TTR amyloidosis (no evidence of plasma call dyscrasia and positive TTR&#xD;
             staining of amyloid in tissue biopsy)&#xD;
&#xD;
          -  Able and willing to provide informed consent to participate in the study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Serious non-cardiac medical illness which will preclude research study participation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sharmila Dorbala, MBBS, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Dorbala S, Vangala D, Semer J, Strader C, Bruyere JR Jr, Di Carli MF, Moore SC, Falk RH. Imaging cardiac amyloidosis: a pilot study using (1)(8)F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. 2014 Sep;41(9):1652-62. doi: 10.1007/s00259-014-2787-6. Epub 2014 May 20.</citation>
    <PMID>24841414</PMID>
  </results_reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>September 4, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2012</study_first_posted>
  <results_first_submitted>January 22, 2022</results_first_submitted>
  <results_first_submitted_qc>March 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 13, 2022</results_first_posted>
  <last_update_submitted>March 20, 2022</last_update_submitted>
  <last_update_submitted_qc>March 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Sharmila Dorbala</investigator_full_name>
    <investigator_title>Director of Nuclear Cardiology</investigator_title>
  </responsible_party>
  <keyword>Amyloidosis</keyword>
  <keyword>Cardiac</keyword>
  <keyword>Heart</keyword>
  <keyword>Imaging</keyword>
  <keyword>Diagnosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amyloidosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>January 9, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT01683825/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 9, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT01683825/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>F-18 Florbetapir PET-Cardiac Amyloidosis Subjects</title>
          <description>Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
        <group group_id="P2">
          <title>F-18 Florbetapir PET-Healthy Controls</title>
          <description>Individuals without documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
        <group group_id="P3">
          <title>F-18 Florbetapir PET Cardiac Amyloidosis Reproducibility Arm</title>
          <description>Individuals with documented cardiac amyloidosis will undergo two F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET) scans within 30 days.&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>This table includes baseline data for all 17 amyloidosis subjects including the 7 subjects who underwent a repeat F-18 florbetapir PET/CT scan for reproducibility as baseline characteristics did not change in the short time interval.</population>
      <group_list>
        <group group_id="B1">
          <title>F-18 Florbetapir PET- Subjects With Cardiac Amyloidosis</title>
          <description>Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
        <group group_id="B2">
          <title>F-18 Florbetapir PET- Controls Without Cardiac Amyloidosis</title>
          <description>Individuals without documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
        <group group_id="B3">
          <title>F-18 Florbetapir PET- Subjects With Cardiac Amyloidosis Reproducibility Arm</title>
          <description>Individuals with documented cardiac amyloidosis will undergo two F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET) scans.&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="7"/>
            <count group_id="B4" value="23"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66.8" spread="13.9"/>
                    <measurement group_id="B2" value="57.5" spread="12.2"/>
                    <measurement group_id="B3" value="68.1" spread="5.8"/>
                    <measurement group_id="B4" value="64.8" spread="12.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Type of amyloidosis</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Light chain cardiac amyloidosis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Transthyretin cardiac amyloidosis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Controls without cardiac amyloidosis</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean</title>
        <description>Standardized uptake value (SUV) mean is defined as the mean F-18 florbetapir activity concentration [kBq/ml] measured within the left ventricular myocardial region of interest multiplied by the decay-corrected amount of injected F-18 florbetapir [kBq] normalized to patient weight [g]. In this study we will measure mean left ventricular global myocardial F-18 Florbetapir SUVmean on static images between 4 minutes to 30 minutes post injection of F-18 florbetapir.</description>
        <time_frame>1 day</time_frame>
        <population>10 cardiac amyloidosis subjects, 6 control subjects without cardiac amyloidosis, and 7 subjects with cardiac amyloidosis were included.</population>
        <group_list>
          <group group_id="O1">
            <title>F-18 Florbetapir PET-Cardiac Amyloidosis Subjects</title>
            <description>Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
          </group>
          <group group_id="O2">
            <title>F-18 Florbetapir PET- Controls Without Cardiac Amyloidosis</title>
            <description>Control subjects without documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
          </group>
          <group group_id="O3">
            <title>F-18 Florbetapir PET-Cardiac Amyloidosis Subjects in Reproducibility Arm</title>
            <description>Individuals with documented cardiac amyloidosis will undergo two F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean</title>
          <description>Standardized uptake value (SUV) mean is defined as the mean F-18 florbetapir activity concentration [kBq/ml] measured within the left ventricular myocardial region of interest multiplied by the decay-corrected amount of injected F-18 florbetapir [kBq] normalized to patient weight [g]. In this study we will measure mean left ventricular global myocardial F-18 Florbetapir SUVmean on static images between 4 minutes to 30 minutes post injection of F-18 florbetapir.</description>
          <population>10 cardiac amyloidosis subjects, 6 control subjects without cardiac amyloidosis, and 7 subjects with cardiac amyloidosis were included.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" spread="1.6"/>
                    <measurement group_id="O2" value="1.7" spread="0.9"/>
                    <measurement group_id="O3" value="5.0" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Global Left Ventricular F-18 Florbetapir SUVmean From Scan 1 to Scan 2</title>
        <description>We evaluated change in F-18 florbetapir SUVmean from scan 1 to scan 2 as a percentage value [(SUVmean1 minus SUVmean 2)/(SUVmean 1)*100]. In the 7 participants with cardiac amyloidosis who underwent two studies (median of 7 days apart), the percentage change in F-18 florbetapir SUVmean from scan 1 to scan 2 ranged from -38.5% to +20.8% with a median value of +2.24%.</description>
        <time_frame>Repeat scan was performed a median of 7 days after baseline study (range 1-46 days)</time_frame>
        <population>Subjects with cardiac amyloidosis who underwent two F-18 florbetapir PET/CT scans.</population>
        <group_list>
          <group group_id="O1">
            <title>F-18 Florbetapir PET-Cardiac Amyloidosis Subjects in Reproducibility Arm</title>
            <description>Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Global Left Ventricular F-18 Florbetapir SUVmean From Scan 1 to Scan 2</title>
          <description>We evaluated change in F-18 florbetapir SUVmean from scan 1 to scan 2 as a percentage value [(SUVmean1 minus SUVmean 2)/(SUVmean 1)*100]. In the 7 participants with cardiac amyloidosis who underwent two studies (median of 7 days apart), the percentage change in F-18 florbetapir SUVmean from scan 1 to scan 2 ranged from -38.5% to +20.8% with a median value of +2.24%.</description>
          <population>Subjects with cardiac amyloidosis who underwent two F-18 florbetapir PET/CT scans.</population>
          <units>% change in SUVmean and SD</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.65" spread="19.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 day</time_frame>
      <group_list>
        <group group_id="E1">
          <title>F-18 Florbetapir PET-Cardiac Amyloidosis Subjects</title>
          <description>Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
        <group group_id="E2">
          <title>F-18 Florbetapir PET-Healthy Controls</title>
          <description>Individuals without documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
        <group group_id="E3">
          <title>F-18 Florbetapir PET-Cardiac Amyloidosis Subjects Reproducibility Arm</title>
          <description>Individuals with documented cardiac amyloidosis will undergo two F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET) scans within 30 days.&#xD;
F-18 florbetapir PET: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The sample size is small. But, cardiac amyloidosis is a rare and under diagnosed disease, it is challenging to enroll more subjects. Also, due to urgency for treatment for AL amyloidosis and changes in heart failure therapy, it was challenging to perform 2 scans without changes in therapy for reproducibility assessment. There is an ongoing competing longitudinal study and most subjects chose to participate in that study, limiting recruitment to this study.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Sharmila Dorbala, Director Nuclear Cardiology</name_or_title>
      <organization>Brigham and Women's Hospital</organization>
      <phone>617-732-6290</phone>
      <email>sdorbala@bwh.harvard.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01683825
org study id: 2012P001322
nct id: NCT01683825
lead sponsor: 
has dmc: No
The primary aim of this pilot study is to determine whether amyloid deposits in the heart can
      be measured non-invasively by F-18 florbetapir (Trade Name: Amyvid) positron emission
      tomography (PET) in 30 individuals with documented cardiac amyloidosis. We will also enroll
      15 individuals without cardiac amyloidosis to undergo the F-18 florbetapir imaging as a
      control group.

      The primary hypothesis of this study is that a specific amyloid binding radiotracer will bind
      to the myocardial amyloid deposits and help quantify cardiac amyloid burden.

      A secondary aim of this study is to determine reproducibility of F-18 florbetapir imaging of
      the myocardium.
F-18 florbetapir has been studied in multiple clinical trials to image beta-amyloid
      deposition in the brain of subjects with Alzheimers' disease. Florbetapir F-18 has been well
      tolerated in studies of more than 2000 human subjects. Biodistribution studies in humans
      revealed predominantly hepatobiliary excretion. The tracer clears rapidly from the blood pool
      in about 20 minutes. This radiotracer has been recently approved for clinical imaging of
      brain amyloid in subjects with suspected Alzheimers disease. The investigators propose to
      test this FDA approved radiotracer for an off label indication in a pilot study to evaluate
      its potential utility, if any, to image cardiac amyloidosis.

      Amyloid related heart disease is associated with LV wall thickening due to infiltration;
      however, this myocardial wall thickening is not definitively distinguishable from left
      ventricular myocyte hypertrophy from increased afterload to the heart from hypertension or
      aortic stenosis. Typically myocardial or other tissue biopsy with typical echo features of
      amyloidosis is required for confirmation of amyloidosis. This pilot study is designed to
      understand whether cardiac amyloid burden can be measured using a specific radiotracer
      targeted against amyloid protein (F-18 Florbetapir). At this point it is unknown of F-18
      Florbetapir will bind to either AL or TTR amyloid protein or to both of them or to neither of
      them. The investigators would like to study 15 patients with AL and 15 patients with TTR
      amyloidosis to understand these differences if any. The investigators also seek to understand
      if the signal to noise ratio of the circulating amyloid protein in the blood pool (AL amyloid
      disease) allows for good differentiation of myocardial amyloid uptake. 15 individuals without
      cardiac amyloidosis will also be enrolled as controls for this study.

      The purpose of the proposed research study is to examine in detail, using quantitative PET,
      myocardial F-18 Florbetapir uptake in cardiac amyloidosis in order to better understand
      mechanisms of heart damage in this disease. A secondary aim of this study is to determine
      reproducibility of F-18 florbetapir imaging of the myocardium in a subset of patients with
      amyloidosis who return for a second F-18 florbetapir scan within 30 days.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Mean Left Ventricular Myocardial F-18 Florbetapir SUVmean
time frame: 1 day
description: Standardized uptake value (SUV) mean is defined as the mean F-18 florbetapir activity concentration [kBq/ml] measured within the left ventricular myocardial region of interest multiplied by the decay-corrected amount of injected F-18 florbetapir [kBq] normalized to patient weight [g]. In this study we will measure mean left ventricular global myocardial F-18 Florbetapir SUVmean on static images between 4 minutes to 30 minutes post injection of F-18 florbetapir.
measure: Percent Change in Global Left Ventricular F-18 Florbetapir SUVmean From Scan 1 to Scan 2
time frame: Repeat scan was performed a median of 7 days after baseline study (range 1-46 days)
description: We evaluated change in F-18 florbetapir SUVmean from scan 1 to scan 2 as a percentage value [(SUVmean1 minus SUVmean 2)/(SUVmean 1)*100]. In the 7 participants with cardiac amyloidosis who underwent two studies (median of 7 days apart), the percentage change in F-18 florbetapir SUVmean from scan 1 to scan 2 ranged from -38.5% to +20.8% with a median value of +2.24%.
arm group label: F-18 florbetapir PET-Amyloid Subjects
arm group type: Experimental
description: Individuals with documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).
arm group label: F-18 florbetapir PET-Healthy Controls
arm group type: Other
description: Individuals without documented cardiac amyloidosis will undergo F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET).
arm group label: F-18 florbetapir PET-Amyloid Reproducibility Subjects
arm group type: Experimental
description: Some of the individuals with documented cardiac amyloidosis from arm 1 will undergo a second F-18 florbetapir (Trade Name: Amyvid) positron emission tomography (PET) within 30 days to measure reproducibility
intervention type: Drug
intervention name: F-18 florbetapir PET
description: Cardiac PET images will be obtained following injection of F-18 labeled Florbetapir (Trade Name: Amyvid)
arm group label: F-18 florbetapir PET-Amyloid Reproducibility Subjects
arm group label: F-18 florbetapir PET-Amyloid Subjects
arm group label: F-18 florbetapir PET-Healthy Controls
other name: F-18 labeled Florbetapir (Trade Name: Amyvid)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Sharmila Dorbala, MBBS, MPH
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
citation: Dorbala S, Vangala D, Semer J, Strader C, Bruyere JR Jr, Di Carli MF, Moore SC, Falk RH. Imaging cardiac amyloidosis: a pilot study using (1)(8)F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. 2014 Sep;41(9):1652-62. doi: 10.1007/s00259-014-2787-6. Epub 2014 May 20.
PMID: 24841414
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Sharmila Dorbala
investigator title: Director of Nuclear Cardiology
mesh term: Amyloidosis
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The sample size is small. But, cardiac amyloidosis is a rare and under diagnosed disease, it is challenging to enroll more subjects. Also, due to urgency for treatment for AL amyloidosis and changes in heart failure therapy, it was challenging to perform 2 scans without changes in therapy for reproducibility assessment. There is an ongoing competing longitudinal study and most subjects chose to participate in that study, limiting recruitment to this study.
point of contact: 