Biomarkers of Iron Homeostasis and Responses to Cystic Fibrosis Pulmonary Exacerbation (CFPE) Treatment

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ClinicalTrials.gov Identifier: NCT02188758

Recruitment Status : Completed

First Posted : July 14, 2014

Last Update Posted : March 13, 2018

Sponsor:

Collaborator:

Maine Medical Center

Information provided by (Responsible Party):

Alex H. Gifford, Dartmouth-Hitchcock Medical Center

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment
Cystic Fibrosis	Other: Adults - CFPE Treatment

Study Design

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Study Type :	Observational
Actual Enrollment :	20 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Do Changes in Serum Hepcidin-25 Concentration Predict Cystic Fibrosis Pulmonary Exacerbation (CFPE) Treatment Responses?
Actual Study Start Date :	July 2014
Actual Primary Completion Date :	December 2017
Actual Study Completion Date :	January 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis Iron

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Adults - CFPE Treatment Other: CF Pulmonary Exacerbation (CFPE) Treatment	Other: Adults - CFPE Treatment 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.

Outcome Measures

Primary Outcome Measures :

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 ]
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.

Secondary Outcome Measures :

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 ]
Post- to pre-treatment ratio for FEV1% for each subject.
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 ]
Post- to pre-treatment ratio for BMI for each subject.
Change in CFRSD-CRISS Score After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
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.
Change in Serum Iron After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for serum iron concentration for each subject.
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 ]
Post- to pre-treatment ratio for serum interleukin-6 (IL-6) concentration for each subject.
Change in Sputum Iron Content After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for sputum iron content for each subject.
Change in Serum EPO Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for serum erythropoietin (EPO) for each subject.
Change in Transferrin Saturation After Hospitalization for CF Pulmonary Exacerbation Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for transferrin saturation for each subject.
Change in Serum TREM-1 Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for serum triggering receptor expressed on myeloid cells-1 (TREM-1) for each subject.
Change in Serum sIL-6R Concentration After Hospitalization for CF Pulmonary Exacerbation Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for serum soluble IL-6 receptor (sIL-6R) concentration for each subject.
Change in Hemoglobin Concentration After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for serum hemoglobin concentration for each subject.

Other Outcome Measures:

Change in Sputum SDI After Hospitalization for CF Pulmonary Exacerbation (CFPE) Treatment [ Time Frame: Duration of hospitalization, an expected average of 12 days ]
Post- to pre-treatment ratio for Simpson Diversity Index (SDI) for each subject.
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 ]
Post- to pre-treatment ratios for selected Pseudomonas aeruginosa mRNA transcript levels.
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 ]
Post- to pre-treatment ratios for selected mRNA transcript levels.

Biospecimen Retention: Samples With DNA

Bacterial DNA and RNA will be isolated from sputum samples and stored for future analyses.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Patients greater than

Criteria

Inclusion Criteria (required at screening visit):

Diagnosis of CF confirmed by history of positive chloride sweat test and/or CFTR mutation analysis;
History of consistent sputum production on most occasions;
FEV1% greater than or equal to 75% of best measurement in previous 6 months;
1 or more hospitalizations for CFPE treatment with intravenous antibiotics within the previous year;
Absence of CFPE (i.e., Akron Pulmonary Exacerbation Score <5);
Not admitted to hospital within the previous 3 weeks;
Body weight greater than or equal to 75% of best measurement in previous 6 months;
Provision of signed informed-consent to study protocol;
18<Age>65

Exclusion Criteria:

Women who are pregnant or lactating;
Subject does not meet Inclusion criteria;
Recent and/or persistent visible blood in sputum (hemoptysis);
Rescue use of oral antibiotics within the previous 3 weeks, defined as antibiotic use for health deterioration rather than chronic suppression

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02188758

Locations

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United States, Maine
Maine Medical Center
South Portland, Maine, United States, 04106
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756

Sponsors and Collaborators

Dartmouth-Hitchcock Medical Center

Maine Medical Center

More Information

Publications:

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.

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.

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.

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.

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.

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Responsible Party:	Alex H. Gifford, Associate Professor of Medicine, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:	NCT02188758
Other Study ID Numbers:	D14136 KL2TR001088 ( U.S. NIH Grant/Contract )
First Posted:	July 14, 2014 Key Record Dates
Last Update Posted:	March 13, 2018
Last Verified:	March 2018

Keywords provided by Alex H. Gifford, Dartmouth-Hitchcock Medical Center:


iron hepcidin-25 pulmonary exacerbation interleukin-6

Additional relevant MeSH terms:

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Cystic Fibrosis Pulmonary Fibrosis Fibrosis Pathologic Processes Pancreatic Diseases	Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases

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