<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/NCT02188758</url>
  </required_header>
  <id_info>
    <org_study_id>D14136</org_study_id>
    <secondary_id>KL2TR001088</secondary_id>
    <nct_id>NCT02188758</nct_id>
  </id_info>
  <brief_title>Biomarkers of Iron Homeostasis and Responses to Cystic Fibrosis Pulmonary Exacerbation (CFPE) Treatment</brief_title>
  <official_title>Do Changes in Serum Hepcidin-25 Concentration Predict Cystic Fibrosis Pulmonary Exacerbation (CFPE) Treatment Responses?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dartmouth-Hitchcock Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MaineHealth</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dartmouth-Hitchcock Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to identify chemical compounds in the blood and sputum (i.e.,&#xD;
      biomarkers) that are associated with objective measurements of health status in patients with&#xD;
      cystic fibrosis (CF). This study builds upon observations that blood levels of hepcidin-25, a&#xD;
      protein that regulates how the body uses and stores iron, vary during CF pulmonary&#xD;
      exacerbation (CFPE).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">January 2018</completion_date>
  <primary_completion_date type="Actual">December 2017</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Serum Hepcidin-25 Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>The primary endpoint of this study is the characterization of 3 groups (i.e., &quot;low,&quot; &quot;intermediate,&quot; and &quot;high&quot;) of serum hepcidin-25 responders to CFPE treatment. Response will be defined as the ratio of post- to pre-treatment serum hepcidin-25 concentration for each subject.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Percent-Predicted Forced Expiratory Volume in One Second (FEV1%) After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for FEV1% for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Mass Index (BMI) After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for BMI for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CFRSD-CRISS Score After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>CFRSD-CRISS is a patient-reported outcome (PRO) instrument developed by the Seattle Quality of Life Group at the University of Washington and used herein under license to evaluate the severity of symptoms of CF in adults and adolescents (≥12 years) with a chronic respiratory infection. Symptoms assessed in the CFRSD-CRISS are: difficulty breathing, cough, cough up mucus, chest tightness, wheeze, feeling feverish, tired, and chills/sweats. The 8 items quantify symptom severity for the previous 24 hours to capture the magnitude of symptoms in stable CF, during medically treated CF exacerbations, and during recovery from an exacerbation. We will determine the within-subject differences in CFRSD-CRISS score associated with CFPE treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Iron After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for serum iron concentration for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum Interleukin-6 (IL-6) Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for serum interleukin-6 (IL-6) concentration for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sputum Iron Content After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for sputum iron content for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum EPO Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for serum erythropoietin (EPO) for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Transferrin Saturation After Hospitalization for CF Pulmonary Exacerbation Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for transferrin saturation for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum TREM-1 Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for serum triggering receptor expressed on myeloid cells-1 (TREM-1) for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Serum sIL-6R Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for serum soluble IL-6 receptor (sIL-6R) concentration for each subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hemoglobin Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for serum hemoglobin concentration for each subject.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Sputum SDI After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratio for Simpson Diversity Index (SDI) for each subject.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Sputum Pseudomonas aeruginosa Gene Expression After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratios for selected Pseudomonas aeruginosa mRNA transcript levels.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Peripheral Blood Mononuclear Cell (PBMC) Gene Expression After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment</measure>
    <time_frame>Duration of hospitalization, an expected average of 12 days</time_frame>
    <description>Post- to pre-treatment ratios for selected mRNA transcript levels.</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">20</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Adults - CFPE Treatment</arm_group_label>
    <description>Other: CF Pulmonary Exacerbation (CFPE) Treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Adults - CFPE Treatment</intervention_name>
    <description>Hospitalization for comprehensive treatment of CF pulmonary exacerbation, including intravenous (IV) antibiotics, nutritional assessment and support, airway clearance of mucus, use of inhaled mucolytic agents and bronchodilators, glycemic control with insulin, and psychosocial support.</description>
    <arm_group_label>Adults - CFPE Treatment</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Bacterial DNA and RNA will be isolated from sputum samples and stored for future analyses.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients greater than&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria (required at screening visit):&#xD;
&#xD;
          -  Diagnosis of CF confirmed by history of positive chloride sweat test and/or CFTR&#xD;
             mutation analysis;&#xD;
&#xD;
          -  History of consistent sputum production on most occasions;&#xD;
&#xD;
          -  FEV1% greater than or equal to 75% of best measurement in previous 6 months;&#xD;
&#xD;
          -  1 or more hospitalizations for CFPE treatment with intravenous antibiotics within the&#xD;
             previous year;&#xD;
&#xD;
          -  Absence of CFPE (i.e., Akron Pulmonary Exacerbation Score &lt;5);&#xD;
&#xD;
          -  Not admitted to hospital within the previous 3 weeks;&#xD;
&#xD;
          -  Body weight greater than or equal to 75% of best measurement in previous 6 months;&#xD;
&#xD;
          -  Provision of signed informed-consent to study protocol;&#xD;
&#xD;
          -  18&lt;Age&gt;65&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant or lactating;&#xD;
&#xD;
          -  Subject does not meet Inclusion criteria;&#xD;
&#xD;
          -  Recent and/or persistent visible blood in sputum (hemoptysis);&#xD;
&#xD;
          -  Rescue use of oral antibiotics within the previous 3 weeks, defined as antibiotic use&#xD;
             for health deterioration rather than chronic suppression&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Maine Medical Center</name>
      <address>
        <city>South Portland</city>
        <state>Maine</state>
        <zip>04106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Gifford AH. What is hepcidin telling us about the natural history of cystic fibrosis? J Cyst Fibros. 2015 Jan;14(1):155-7. doi: 10.1016/j.jcf.2014.03.012. Epub 2014 Apr 30. No abstract available.</citation>
    <PMID>24795218</PMID>
  </reference>
  <reference>
    <citation>Gifford AH, Alexandru DM, Li Z, Dorman DB, Moulton LA, Price KE, Hampton TH, Sogin ML, Zuckerman JB, Parker HW, Stanton BA, O'Toole GA. Iron supplementation does not worsen respiratory health or alter the sputum microbiome in cystic fibrosis. J Cyst Fibros. 2014 May;13(3):311-8. doi: 10.1016/j.jcf.2013.11.004. Epub 2013 Dec 13.</citation>
    <PMID>24332997</PMID>
  </reference>
  <reference>
    <citation>Gifford AH. Hemoglobin &lt;/= 12.9 g/dl predicts risk of antibiotic treatment in cystic fibrosis. J Cyst Fibros. 2014 Jan;13(1):114-5. doi: 10.1016/j.jcf.2013.06.007. Epub 2013 Jul 16. No abstract available.</citation>
    <PMID>23867071</PMID>
  </reference>
  <reference>
    <citation>Gifford AH, Moulton LA, Dorman DB, Olbina G, Westerman M, Parker HW, Stanton BA, O'Toole GA. Iron homeostasis during cystic fibrosis pulmonary exacerbation. Clin Transl Sci. 2012 Aug;5(4):368-73. doi: 10.1111/j.1752-8062.2012.00417.x. Epub 2012 Jun 1.</citation>
    <PMID>22883617</PMID>
  </reference>
  <reference>
    <citation>Gifford AH, Miller SD, Jackson BP, Hampton TH, O'Toole GA, Stanton BA, Parker HW. Iron and CF-related anemia: expanding clinical and biochemical relationships. Pediatr Pulmonol. 2011 Feb;46(2):160-5. doi: 10.1002/ppul.21335. Epub 2010 Oct 20.</citation>
    <PMID>20963784</PMID>
  </reference>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>July 9, 2014</study_first_submitted>
  <study_first_submitted_qc>July 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 14, 2014</study_first_posted>
  <last_update_submitted>March 9, 2018</last_update_submitted>
  <last_update_submitted_qc>March 9, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dartmouth-Hitchcock Medical Center</investigator_affiliation>
    <investigator_full_name>Alex H. Gifford</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>iron</keyword>
  <keyword>hepcidin-25</keyword>
  <keyword>pulmonary exacerbation</keyword>
  <keyword>interleukin-6</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
    <mesh_term>Pulmonary Fibrosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <!-- 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/NCT02188758
org study id: D14136
secondary id: KL2TR001088
nct id: NCT02188758
lead sponsor: 
collaborator: 
has dmc: No
The goal of this study is to identify chemical compounds in the blood and sputum (i.e.,
      biomarkers) that are associated with objective measurements of health status in patients with
      cystic fibrosis (CF). This study builds upon observations that blood levels of hepcidin-25, a
      protein that regulates how the body uses and stores iron, vary during CF pulmonary
      exacerbation (CFPE).
observational model: Cohort
time perspective: Prospective
measure: Change in Serum Hepcidin-25 Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: The primary endpoint of this study is the characterization of 3 groups (i.e., "low," "intermediate," and "high") of serum hepcidin-25 responders to CFPE treatment. Response will be defined as the ratio of post- to pre-treatment serum hepcidin-25 concentration for each subject.
measure: Change in Percent-Predicted Forced Expiratory Volume in One Second (FEV1%) After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for FEV1% for each subject.
measure: Change in Body Mass Index (BMI) After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for BMI for each subject.
measure: Change in CFRSD-CRISS Score After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: CFRSD-CRISS is a patient-reported outcome (PRO) instrument developed by the Seattle Quality of Life Group at the University of Washington and used herein under license to evaluate the severity of symptoms of CF in adults and adolescents (≥12 years) with a chronic respiratory infection. Symptoms assessed in the CFRSD-CRISS are: difficulty breathing, cough, cough up mucus, chest tightness, wheeze, feeling feverish, tired, and chills/sweats. The 8 items quantify symptom severity for the previous 24 hours to capture the magnitude of symptoms in stable CF, during medically treated CF exacerbations, and during recovery from an exacerbation. We will determine the within-subject differences in CFRSD-CRISS score associated with CFPE treatment.
measure: Change in Serum Iron After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for serum iron concentration for each subject.
measure: Change in Serum Interleukin-6 (IL-6) Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for serum interleukin-6 (IL-6) concentration for each subject.
measure: Change in Sputum Iron Content After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for sputum iron content for each subject.
measure: Change in Serum EPO Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for serum erythropoietin (EPO) for each subject.
measure: Change in Transferrin Saturation After Hospitalization for CF Pulmonary Exacerbation Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for transferrin saturation for each subject.
measure: Change in Serum TREM-1 Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for serum triggering receptor expressed on myeloid cells-1 (TREM-1) for each subject.
measure: Change in Serum sIL-6R Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for serum soluble IL-6 receptor (sIL-6R) concentration for each subject.
measure: Change in Hemoglobin Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for serum hemoglobin concentration for each subject.
measure: Change in Sputum SDI After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratio for Simpson Diversity Index (SDI) for each subject.
measure: Change in Sputum Pseudomonas aeruginosa Gene Expression After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratios for selected Pseudomonas aeruginosa mRNA transcript levels.
measure: Change in Peripheral Blood Mononuclear Cell (PBMC) Gene Expression After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment
time frame: Duration of hospitalization, an expected average of 12 days
description: Post- to pre-treatment ratios for selected mRNA transcript levels.
arm group label: Adults - CFPE Treatment
description: Other: CF Pulmonary Exacerbation (CFPE) Treatment
intervention type: Other
intervention name: Adults - CFPE Treatment
description: Hospitalization for comprehensive treatment of CF pulmonary exacerbation, including intravenous (IV) antibiotics, nutritional assessment and support, airway clearance of mucus, use of inhaled mucolytic agents and bronchodilators, glycemic control with insulin, and psychosocial support.
arm group label: Adults - CFPE Treatment
Bacterial DNA and RNA will be isolated from sputum samples and stored for future analyses.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
facility: 
country: United States
citation: Gifford AH. What is hepcidin telling us about the natural history of cystic fibrosis? J Cyst Fibros. 2015 Jan;14(1):155-7. doi: 10.1016/j.jcf.2014.03.012. Epub 2014 Apr 30. No abstract available.
PMID: 24795218
citation: Gifford AH, Alexandru DM, Li Z, Dorman DB, Moulton LA, Price KE, Hampton TH, Sogin ML, Zuckerman JB, Parker HW, Stanton BA, O'Toole GA. Iron supplementation does not worsen respiratory health or alter the sputum microbiome in cystic fibrosis. J Cyst Fibros. 2014 May;13(3):311-8. doi: 10.1016/j.jcf.2013.11.004. Epub 2013 Dec 13.
PMID: 24332997
citation: Gifford AH. Hemoglobin </= 12.9 g/dl predicts risk of antibiotic treatment in cystic fibrosis. J Cyst Fibros. 2014 Jan;13(1):114-5. doi: 10.1016/j.jcf.2013.06.007. Epub 2013 Jul 16. No abstract available.
PMID: 23867071
citation: Gifford AH, Moulton LA, Dorman DB, Olbina G, Westerman M, Parker HW, Stanton BA, O'Toole GA. Iron homeostasis during cystic fibrosis pulmonary exacerbation. Clin Transl Sci. 2012 Aug;5(4):368-73. doi: 10.1111/j.1752-8062.2012.00417.x. Epub 2012 Jun 1.
PMID: 22883617
citation: Gifford AH, Miller SD, Jackson BP, Hampton TH, O'Toole GA, Stanton BA, Parker HW. Iron and CF-related anemia: expanding clinical and biochemical relationships. Pediatr Pulmonol. 2011 Feb;46(2):160-5. doi: 10.1002/ppul.21335. Epub 2010 Oct 20.
PMID: 20963784
responsible party type: Principal Investigator
investigator affiliation: Dartmouth-Hitchcock Medical Center
investigator full name: Alex H. Gifford
investigator title: Associate Professor of Medicine
mesh term: Cystic Fibrosis
mesh term: Pulmonary Fibrosis
mesh term: Fibrosis