<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/NCT01688895</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 08-0959-04</org_study_id>
    <secondary_id>HSM12-00307</secondary_id>
    <secondary_id>U54DK083909</secondary_id>
    <nct_id>NCT01688895</nct_id>
  </id_info>
  <brief_title>Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact</brief_title>
  <official_title>Erythropoietic Protoporphyrias: Studies of the Natural History, Genotype-Phenotype Correlations, and Psychosocial Impact</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Icahn School of Medicine at Mount Sinai</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rare Diseases Clinical Research Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Office of Rare Diseases (ORD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The initial objective of this protocol is to assemble a well-documented group of patients&#xD;
      with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive&#xD;
      Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical,&#xD;
      biochemical, and genetic studies. The long-term objectives are (1) to conduct a longitudinal&#xD;
      investigation of the natural history, complications, and therapeutic outcomes in people with&#xD;
      erythropoietic protoporphyria, (2) to systematically investigate the psychological effects of&#xD;
      the erythropoietic protoporphyrias on children and adults, and (3) to investigate the&#xD;
      correlation between the identified genotypes and the resulting clinical presentation, also&#xD;
      determining the possible interaction of other genetic markers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The porphyrias are a group of rare metabolic diseases that may present in childhood or adult&#xD;
      life and are due to deficiencies of enzymes in the heme biosynthetic pathway. The most common&#xD;
      manifestations are related to accumulation of intermediates in the pathway and usually occur&#xD;
      as acute neurological attacks (as in the acute or hepatic porphyrias), or cutaneous&#xD;
      photosensitivity (as in the cutaneous porphyrias, including the erythropoietic&#xD;
      protoporphyrias). Multiple mutations have been identified in each of the porphyrias. The risk&#xD;
      of disability or death from these disorders is significant, in part because diagnosis is&#xD;
      often delayed due to lack of adoption of diagnostic testing in clinical practice. Moreover,&#xD;
      the natural history of these disorders is not well described and it is not known what&#xD;
      determines differences in outcomes. New therapies are needed. For existing therapies,&#xD;
      high-quality evidence on short and long term efficacy and safety is generally lacking.&#xD;
      Therefore, the purpose of this study of a large group of patients with EPP and XLP is to&#xD;
      provide a better understanding of the natural history of these disorders, as affected by&#xD;
      available therapies, and to aid in developing new forms of treatment. Much of the data&#xD;
      collected on subjects as participants in the Longitudinal Study of the Porphyrias will be&#xD;
      accessed for this study specific to the investigation of the erythropoietic protoporphyrias.&#xD;
      To maximize the information that can be informative in our objectives, additional data will&#xD;
      be collected, including additional biochemical findings and EPP-specific psychosocial&#xD;
      parameters.&#xD;
&#xD;
      The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a&#xD;
      Rare Diseases Clinical Research Network (RDCRN) in collaboration with other NIH Institutes&#xD;
      and currently has funded 19 rare diseases clinical research consortia and one Data Management&#xD;
      and Coordinating Center. The Porphyrias Consortium was created as part of the RDCRN, to study&#xD;
      the human porphyrias. The Porphyrias Consortium is a consortium of the academic institutions&#xD;
      listed in the participating institutions table. All Centers in the Porphyrias Consortium are&#xD;
      participating in this study. Additional centers may be added if funding is available.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">July 1, 2019</completion_date>
  <primary_completion_date type="Actual">July 1, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The Hospital Anxiety and Depression Scale (HADS)</measure>
    <time_frame>1 weeks</time_frame>
    <description>Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, subscales 0-21, with full range from 0 to 42, with higher score indicating more severe anxiety or depression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Illness Perception Questionnaire Revised (IPQR)</measure>
    <time_frame>1 week</time_frame>
    <description>Each item is scored on a likert scale from 1 (strongly disagree) to 5 (strongly agree). Items within each domain were totaled for final domain scores.&#xD;
Seven domains - Timeline (score 5-25), Consequences (score 6-30), Personal Control (score 6-30), Treatment Control (score 3-15), Illness Coherence (score 5-25), Timeline-Cyclical (score 4-20), and Emotional Representations (score 6-30). A modified version without the identity component was used as it was not applicable in EPP.&#xD;
Higher scores domains indicate overall strong beliefs that the disease is chronic and has a negative impact.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>EPP-Specific Tool</measure>
    <time_frame>1 week</time_frame>
    <description>Each item was scored from 0-3 on a Likert scale. There are 2 domains: S=disease severity and Q=QoL. Total scale for each domain transferred to 0-100 scale. Higher scores for the S domain reflect lower severity, and higher satisfaction/QoL for the Q domain. Total Score from 0-100, with higher score indicating higher quality of life.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sleep Disturbance PROMIS Scores</measure>
    <time_frame>baseline</time_frame>
    <description>Sleep Subscales: Pain Interference, Depression, Physical Function, Fatigue, Anxiety, Sleep Disturbance, Satisfaction with Social Roles, each subscale scored from 0-100 with higher score indicating more symptoms affecting sleep.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">150</enrollment>
  <condition>Erythropoietic Protoporphyria</condition>
  <condition>EPP</condition>
  <condition>X-Linked Protoporphyria</condition>
  <condition>XLP</condition>
  <condition>XLPP</condition>
  <condition>X-Linked Dominant Erythropoietic Protoporphyria</condition>
  <condition>XLEPP</condition>
  <condition>XLDP</condition>
  <arm_group>
    <arm_group_label>Participants with Protoporphyrias</arm_group_label>
    <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      DNA extracted from peripheral blood sample or buccal (inside cheek) sampling for DNA&#xD;
      analysis; whole blood in ACD anti-coagulant to establish a lymphoid cell line, red blood&#xD;
      cells and plasma for biochemical assays.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Subjects will be recruited from the following resources:&#xD;
&#xD;
          1. Patients followed by one of the Investigators&#xD;
&#xD;
          2. The American Porphyria Foundation (APF)&#xD;
&#xD;
          3. The Rare Diseases Clinical Research Network (RDCRN) Contact Registry&#xD;
&#xD;
          4. Non-study Physician referrals&#xD;
&#xD;
          5. Self-referrals, including family members of individuals diagnosed with Porphyria&#xD;
             (proband) and other individuals who may have heard about the study from other subjects&#xD;
             or prospective subjects.&#xD;
&#xD;
          6. Medical Records Review&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All subjects must also be enrolled in the Longitudinal Study of the Porphyrias.&#xD;
&#xD;
          -  Willing to sign informed consent form&#xD;
&#xD;
          -  Biochemical findings - A marked increase in erythrocyte protoporphyrin [total&#xD;
             erythrocyte protoporphyrin &gt;200 ug/dL, or more than 1.5-fold increase (relative to ULN&#xD;
             of 80 ug/dL)], with a predominance of free protoporphyrin (85-100% in EPP and 50-85%&#xD;
             in XLP).&#xD;
&#xD;
          -  Molecular findings - one of the following:&#xD;
&#xD;
               1. A disease causing FECH mutation trans to the IVS3-48C&gt;T low expression FECH&#xD;
                  allele&#xD;
&#xD;
               2. Two disease-causing FECH mutations&#xD;
&#xD;
               3. A gain-of-function ALAS-2 C-terminal deletion/exon 11 mutation (in XLP). If no&#xD;
                  mutation is found and subjects fulfill criteria 1-3 they are eligible for&#xD;
                  enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  cases with elevations of porphyrins in urine, plasma or erythrocytes due to other&#xD;
             diseases (i.e. secondary porphyrinuria or porphyrinemia), such as liver and bone&#xD;
             marrow diseases [Gibson 2000].&#xD;
&#xD;
          -  patients with a prior diagnosis of porphyria that cannot be documented by review of&#xD;
             existing medical records or repeat biochemical or DNA testing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Manisha Balwani, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama, Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-0012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wake Forest University Health Sciences</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.rarediseasesnetwork.org/cms/porphyrias</url>
    <description>Website for the Rare Diseases Clinical Research Network (RDCRN) Porphyrias Consortium (PC)</description>
  </link>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>September 14, 2012</study_first_submitted>
  <study_first_submitted_qc>September 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <results_first_submitted>March 5, 2020</results_first_submitted>
  <results_first_submitted_qc>April 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 17, 2020</results_first_posted>
  <last_update_submitted>April 13, 2020</last_update_submitted>
  <last_update_submitted_qc>April 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>erythropoietic</keyword>
  <keyword>protoporphyria</keyword>
  <keyword>cutaneous</keyword>
  <keyword>porphyria</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Protoporphyria, Erythropoietic</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 26, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/95/NCT01688895/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Adult Patients With EPP/XLP</title>
          <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="150"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="150"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Adult Patients With EPP/XLP</title>
          <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="150"/>
          </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="40.9" spread="14.5"/>
                  </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="66"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="144"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Protoporphyria Type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Erythropoietic Protoporphyria - EPP</title>
                  <measurement_list>
                    <measurement group_id="B1" value="143"/>
                  </measurement_list>
                </category>
                <category>
                  <title>X-Linked Protoporphyria - XLP</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown type</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age at Onset of Symptoms</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.2" spread="4.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Hospital Anxiety and Depression Scale (HADS)</title>
        <description>Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, subscales 0-21, with full range from 0 to 42, with higher score indicating more severe anxiety or depression.</description>
        <time_frame>1 weeks</time_frame>
        <population>Data only for those who completed instrument included. A protocol modification to add the HADS tool was done after study initiation, therefore not all subjects received all tools.</population>
        <group_list>
          <group group_id="O1">
            <title>Adult Patients With EPP/XLP</title>
            <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</description>
          </group>
        </group_list>
        <measure>
          <title>The Hospital Anxiety and Depression Scale (HADS)</title>
          <description>Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, subscales 0-21, with full range from 0 to 42, with higher score indicating more severe anxiety or depression.</description>
          <population>Data only for those who completed instrument included. A protocol modification to add the HADS tool was done after study initiation, therefore not all subjects received all tools.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="103"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anxiety</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.6" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Illness Perception Questionnaire Revised (IPQR)</title>
        <description>Each item is scored on a likert scale from 1 (strongly disagree) to 5 (strongly agree). Items within each domain were totaled for final domain scores.&#xD;
Seven domains - Timeline (score 5-25), Consequences (score 6-30), Personal Control (score 6-30), Treatment Control (score 3-15), Illness Coherence (score 5-25), Timeline-Cyclical (score 4-20), and Emotional Representations (score 6-30). A modified version without the identity component was used as it was not applicable in EPP.&#xD;
Higher scores domains indicate overall strong beliefs that the disease is chronic and has a negative impact.</description>
        <time_frame>1 week</time_frame>
        <population>Data only for those who completed instrument included. A protocol modification to add the IPQR tool was done after study initiation, therefore not all subjects received all tools.</population>
        <group_list>
          <group group_id="O1">
            <title>Adult Patients With EPP/XLP</title>
            <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</description>
          </group>
        </group_list>
        <measure>
          <title>Illness Perception Questionnaire Revised (IPQR)</title>
          <description>Each item is scored on a likert scale from 1 (strongly disagree) to 5 (strongly agree). Items within each domain were totaled for final domain scores.&#xD;
Seven domains - Timeline (score 5-25), Consequences (score 6-30), Personal Control (score 6-30), Treatment Control (score 3-15), Illness Coherence (score 5-25), Timeline-Cyclical (score 4-20), and Emotional Representations (score 6-30). A modified version without the identity component was used as it was not applicable in EPP.&#xD;
Higher scores domains indicate overall strong beliefs that the disease is chronic and has a negative impact.</description>
          <population>Data only for those who completed instrument included. A protocol modification to add the IPQR tool was done after study initiation, therefore not all subjects received all tools.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Timeline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.4" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Consequences</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.2" spread="4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Personal Control</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.0" spread="4.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Control</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.2" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Illness Coherence</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.0" spread="4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Timeline - Cyclical</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.5" spread="3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional Representations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.8" spread="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>EPP-Specific Tool</title>
        <description>Each item was scored from 0-3 on a Likert scale. There are 2 domains: S=disease severity and Q=QoL. Total scale for each domain transferred to 0-100 scale. Higher scores for the S domain reflect lower severity, and higher satisfaction/QoL for the Q domain. Total Score from 0-100, with higher score indicating higher quality of life.</description>
        <time_frame>1 week</time_frame>
        <population>Data only for those who completed instrument included. A protocol modification to add the EPP-Specific tool was done after study initiation, therefore not all subjects received all tools.</population>
        <group_list>
          <group group_id="O1">
            <title>Adult Patients With EPP/XLP</title>
            <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</description>
          </group>
        </group_list>
        <measure>
          <title>EPP-Specific Tool</title>
          <description>Each item was scored from 0-3 on a Likert scale. There are 2 domains: S=disease severity and Q=QoL. Total scale for each domain transferred to 0-100 scale. Higher scores for the S domain reflect lower severity, and higher satisfaction/QoL for the Q domain. Total Score from 0-100, with higher score indicating higher quality of life.</description>
          <population>Data only for those who completed instrument included. A protocol modification to add the EPP-Specific tool was done after study initiation, therefore not all subjects received all tools.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>S Domain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.9" spread="30.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Q Domain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.8" spread="27.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.3" spread="30.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sleep Disturbance PROMIS Scores</title>
        <description>Sleep Subscales: Pain Interference, Depression, Physical Function, Fatigue, Anxiety, Sleep Disturbance, Satisfaction with Social Roles, each subscale scored from 0-100 with higher score indicating more symptoms affecting sleep.</description>
        <time_frame>baseline</time_frame>
        <population>*Only those subjects who completed the PROMIS was included</population>
        <group_list>
          <group group_id="O1">
            <title>Adult Patients With EPP/XLP</title>
            <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</description>
          </group>
        </group_list>
        <measure>
          <title>Sleep Disturbance PROMIS Scores</title>
          <description>Sleep Subscales: Pain Interference, Depression, Physical Function, Fatigue, Anxiety, Sleep Disturbance, Satisfaction with Social Roles, each subscale scored from 0-100 with higher score indicating more symptoms affecting sleep.</description>
          <population>*Only those subjects who completed the PROMIS was included</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pain Interference</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.1" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Depression</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.1" spread="8.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical Function</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.5" spread="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatigue</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.6" spread="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anxiety</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.3" spread="10.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sleep Disturbance</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.7" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Satisfaction with Social Roles</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.9" spread="9.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 week</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Adult Patients With EPP/XLP</title>
          <description>Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)</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="150"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="150"/>
              </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="150"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Hetanshi Naik</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>212-241-7699</phone>
      <email>hetanshi.naik@mssm.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/NCT01688895
org study id: GCO 08-0959-04
secondary id: HSM12-00307
secondary id: U54DK083909
nct id: NCT01688895
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The initial objective of this protocol is to assemble a well-documented group of patients
      with confirmed diagnoses of the erythropoietic protoporphyrias, including autosomal recessive
      Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) for clinical,
      biochemical, and genetic studies. The long-term objectives are (1) to conduct a longitudinal
      investigation of the natural history, complications, and therapeutic outcomes in people with
      erythropoietic protoporphyria, (2) to systematically investigate the psychological effects of
      the erythropoietic protoporphyrias on children and adults, and (3) to investigate the
      correlation between the identified genotypes and the resulting clinical presentation, also
      determining the possible interaction of other genetic markers.
The porphyrias are a group of rare metabolic diseases that may present in childhood or adult
      life and are due to deficiencies of enzymes in the heme biosynthetic pathway. The most common
      manifestations are related to accumulation of intermediates in the pathway and usually occur
      as acute neurological attacks (as in the acute or hepatic porphyrias), or cutaneous
      photosensitivity (as in the cutaneous porphyrias, including the erythropoietic
      protoporphyrias). Multiple mutations have been identified in each of the porphyrias. The risk
      of disability or death from these disorders is significant, in part because diagnosis is
      often delayed due to lack of adoption of diagnostic testing in clinical practice. Moreover,
      the natural history of these disorders is not well described and it is not known what
      determines differences in outcomes. New therapies are needed. For existing therapies,
      high-quality evidence on short and long term efficacy and safety is generally lacking.
      Therefore, the purpose of this study of a large group of patients with EPP and XLP is to
      provide a better understanding of the natural history of these disorders, as affected by
      available therapies, and to aid in developing new forms of treatment. Much of the data
      collected on subjects as participants in the Longitudinal Study of the Porphyrias will be
      accessed for this study specific to the investigation of the erythropoietic protoporphyrias.
      To maximize the information that can be informative in our objectives, additional data will
      be collected, including additional biochemical findings and EPP-specific psychosocial
      parameters.

      The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) established a
      Rare Diseases Clinical Research Network (RDCRN) in collaboration with other NIH Institutes
      and currently has funded 19 rare diseases clinical research consortia and one Data Management
      and Coordinating Center. The Porphyrias Consortium was created as part of the RDCRN, to study
      the human porphyrias. The Porphyrias Consortium is a consortium of the academic institutions
      listed in the participating institutions table. All Centers in the Porphyrias Consortium are
      participating in this study. Additional centers may be added if funding is available.
observational model: Cohort
time perspective: Other
measure: The Hospital Anxiety and Depression Scale (HADS)
time frame: 1 weeks
description: Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, subscales 0-21, with full range from 0 to 42, with higher score indicating more severe anxiety or depression.
measure: Illness Perception Questionnaire Revised (IPQR)
time frame: 1 week
description: Each item is scored on a likert scale from 1 (strongly disagree) to 5 (strongly agree). Items within each domain were totaled for final domain scores.
Seven domains - Timeline (score 5-25), Consequences (score 6-30), Personal Control (score 6-30), Treatment Control (score 3-15), Illness Coherence (score 5-25), Timeline-Cyclical (score 4-20), and Emotional Representations (score 6-30). A modified version without the identity component was used as it was not applicable in EPP.
Higher scores domains indicate overall strong beliefs that the disease is chronic and has a negative impact.
measure: EPP-Specific Tool
time frame: 1 week
description: Each item was scored from 0-3 on a Likert scale. There are 2 domains: S=disease severity and Q=QoL. Total scale for each domain transferred to 0-100 scale. Higher scores for the S domain reflect lower severity, and higher satisfaction/QoL for the Q domain. Total Score from 0-100, with higher score indicating higher quality of life.
measure: Sleep Disturbance PROMIS Scores
time frame: baseline
description: Sleep Subscales: Pain Interference, Depression, Physical Function, Fatigue, Anxiety, Sleep Disturbance, Satisfaction with Social Roles, each subscale scored from 0-100 with higher score indicating more symptoms affecting sleep.
arm group label: Participants with Protoporphyrias
description: Individuals with a documented diagnosis of Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
DNA extracted from peripheral blood sample or buccal (inside cheek) sampling for DNA
      analysis; whole blood in ACD anti-coagulant to establish a lymphoid cell line, red blood
      cells and plasma for biochemical assays.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Manisha Balwani, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
url: https://www.rarediseasesnetwork.org/cms/porphyrias
description: Website for the Rare Diseases Clinical Research Network (RDCRN) Porphyrias Consortium (PC)
responsible party type: Sponsor
mesh term: Protoporphyria, Erythropoietic
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 