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
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring cystic fibrosis
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)
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
NCT ID
NCT03045198
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
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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