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Effect of Azithromycin on Fatty Acids in CF

Primary Purpose

Cystic Fibrosis

Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Azithromycin
Sponsored by
University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring cystic fibrosis

Eligibility Criteria

10 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Delta 508 homozygous and regularly visiting the CF outpatient clinic Bonn

Exclusion Criteria:

  • clinical or laboratory signs (CRP > 20 mg/L) of an exacerbation,
  • treatment with systemic steroids 14 days preceeding this trial
  • elevated liver function tests (> twice normal range)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Azithromycin

    Arm Description

    oral Azithromycin 10 mg/kg Body weight, max. 500 mg every Monday, Wednesday and Friday for 4 weeks

    Outcomes

    Primary Outcome Measures

    Lipoproteins in Serum (after overnight fast)
    VLDL,LDL,HDL, Cholesterin
    Fatty acids in EDTA-Plasma and erythrocyte membranes (after overnight fast)
    linol acid, arachidon acid, Alpha linolen acid, eicosapentaen acid, Docoshexaen acidsdocosahexaen acid

    Secondary Outcome Measures

    Cytokines in induced sputum and whole blood
    Lipopolysaccharid binding Protein (LBP), interleukin-8 (IL-8) und Tumor necrosis factor Alpha (TNF Alpha)
    ICAM1 (Serum)
    Matrixmetalloprotease 9 (Serum)
    WBC + CRP, IgE, RAST Aspergillus fum, ECP (Serum), Carotin, Vitamin E
    Shwachman-Score
    Clinical score
    Body weight, length
    Lung function test
    VC, FEV1, MEF 25
    Nutrition protocol
    Evaluation of Food intake and calculation of fat composition, Protein etc.
    Resolvins in EDTA plasma

    Full Information

    First Posted
    February 2, 2017
    Last Updated
    July 31, 2018
    Sponsor
    University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)
    Collaborators
    University of Bonn, Goethe University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03045198
    Brief Title
    Effect of Azithromycin on Fatty Acids in CF
    Official Title
    Effect of Azithromycin on Lipoproteins and Docosahexaenoic Acid in Patients With Cystic Fibrosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Unknown status
    Study Start Date
    March 2012 (undefined)
    Primary Completion Date
    December 2018 (Anticipated)
    Study Completion Date
    December 2018 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)
    Collaborators
    University of Bonn, Goethe University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    In collaboration with Dr.Birgit Alteheld, Institute of Nutrional Sciences of the university of Bonn, Germany the following effect is explored: Effect of a 4 week therapy with AZT on synthesis of lipoproteins as well as Docosahexaen and other fatty acids in patients with Cystic Fibrosis (CF). Moreover proinflammatory cytokines in blood and sputum are of interest.
    Detailed Description
    The macrolide azithromycin (AZT) is recommended by Flume in the CF pulmonary Guidelines for long-term treatment of patients with CF chronically colonized with Pseudomonas aeruginosa due to its immunomodulating properties . AZT causes a significant reduction of the proinflammatory cytokine Lipopolysaccharid binding protein (LBP) according to Steinkamp and Schmitt-Grohé. There is an inverse correlation between LBP and lung function. Moreover Schmitt-Grohé and coworkers provided evidence of a positive correlation between the lipoprotein HDL and lung function. Ribeiro and coworkers found an increased expression of Lipid/Cholesterol genes of primary human airway epithelial cultures after treatment with AZT. Freedman and coworkers were able to show decreased levels of Docosahexaen acid in CF patients. The aim of this study is to explore the impact of a 4 week trial of AZT on lipoprotein and fatty acids (docosahexaen acid etc.) synthesis. Delta F508 homozygous patients receive AZT (10 mg/kg body weight resp. max 500 mg) every Monday, Wednesday and Friday for 4 weeks. 20 patients (age 10-60 years) will be recruited. Fatty acids (blood), cytokines (whole blood and induced sputum) and clinical parameters are assessed before and 4 weeks after AZT treatment.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cystic Fibrosis
    Keywords
    cystic fibrosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Single Group Assignment
    Model Description
    CF patients receive for 4 weeks Azithromycin. Study measures are assessed before and after 4 weeks
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Azithromycin
    Arm Type
    Experimental
    Arm Description
    oral Azithromycin 10 mg/kg Body weight, max. 500 mg every Monday, Wednesday and Friday for 4 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    Azithromycin
    Other Intervention Name(s)
    Zithromax
    Primary Outcome Measure Information:
    Title
    Lipoproteins in Serum (after overnight fast)
    Description
    VLDL,LDL,HDL, Cholesterin
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Title
    Fatty acids in EDTA-Plasma and erythrocyte membranes (after overnight fast)
    Description
    linol acid, arachidon acid, Alpha linolen acid, eicosapentaen acid, Docoshexaen acidsdocosahexaen acid
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Secondary Outcome Measure Information:
    Title
    Cytokines in induced sputum and whole blood
    Description
    Lipopolysaccharid binding Protein (LBP), interleukin-8 (IL-8) und Tumor necrosis factor Alpha (TNF Alpha)
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Title
    ICAM1 (Serum)
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Title
    Matrixmetalloprotease 9 (Serum)
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Title
    WBC + CRP, IgE, RAST Aspergillus fum, ECP (Serum), Carotin, Vitamin E
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Title
    Shwachman-Score
    Description
    Clinical score
    Time Frame
    Day 0
    Title
    Body weight, length
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Title
    Lung function test
    Description
    VC, FEV1, MEF 25
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
    Title
    Nutrition protocol
    Description
    Evaluation of Food intake and calculation of fat composition, Protein etc.
    Time Frame
    For 7 days before day 0 and day 28
    Title
    Resolvins in EDTA plasma
    Time Frame
    Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    10 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Delta 508 homozygous and regularly visiting the CF outpatient clinic Bonn Exclusion Criteria: clinical or laboratory signs (CRP > 20 mg/L) of an exacerbation, treatment with systemic steroids 14 days preceeding this trial elevated liver function tests (> twice normal range)
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Sabina Schmitt-Grohé, MD
    Organizational Affiliation
    University Children's Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    Citations:
    PubMed Identifier
    14762183
    Citation
    Freedman SD, Blanco PG, Zaman MM, Shea JC, Ollero M, Hopper IK, Weed DA, Gelrud A, Regan MM, Laposata M, Alvarez JG, O'Sullivan BP. Association of cystic fibrosis with abnormalities in fatty acid metabolism. N Engl J Med. 2004 Feb 5;350(6):560-9. doi: 10.1056/NEJMoa021218.
    Results Reference
    background
    PubMed Identifier
    18701270
    Citation
    Steinkamp G, Schmitt-Grohe S, Doring G, Staab D, Pfrunder D, Beck G, Schubert R, Zielen S. Once-weekly azithromycin in cystic fibrosis with chronic Pseudomonas aeruginosa infection. Respir Med. 2008 Nov;102(11):1643-53. doi: 10.1016/j.rmed.2008.03.009. Epub 2008 Aug 12.
    Results Reference
    background
    PubMed Identifier
    16183806
    Citation
    Schmitt-Grohe S, Hippe V, Igel M, von Bergmann K, Posselt HG, Krahl A, Smaczny C, Wagner TO, Nikolazik W, Schubert R, Lentze MJ, Zielen S. Lipopolysaccharide binding protein, cytokine production in whole blood, and lipoproteins in cystic fibrosis. Pediatr Res. 2005 Nov;58(5):903-7. doi: 10.1203/01.PDR.0000182598.98167.24. Epub 2005 Sep 23.
    Results Reference
    background
    PubMed Identifier
    17761616
    Citation
    Flume PA, O'Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ Jr, Willey-Courand DB, Bujan J, Finder J, Lester M, Quittell L, Rosenblatt R, Vender RL, Hazle L, Sabadosa K, Marshall B; Cystic Fibrosis Foundation, Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007 Nov 15;176(10):957-69. doi: 10.1164/rccm.200705-664OC. Epub 2007 Aug 29.
    Results Reference
    background
    PubMed Identifier
    19503797
    Citation
    Ribeiro CM, Hurd H, Wu Y, Martino ME, Jones L, Brighton B, Boucher RC, O'Neal WK. Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia. PLoS One. 2009 Jun 5;4(6):e5806. doi: 10.1371/journal.pone.0005806.
    Results Reference
    background

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    Effect of Azithromycin on Fatty Acids in CF

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