Effect of Azithromycin on Fatty Acids in CF

Cystic Fibrosis Clinical Trial

Official title:

Effect of Azithromycin on Lipoproteins and Docosahexaenoic Acid in Patients With Cystic Fibrosis

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03045198
• Other study ID #: Sylvia 253/12
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: March 2012
• Est. completion date: December 2018

Study information

• Verified date: July 2018
• Source: University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 20
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Azithromycin

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)	University Hospital, Frankfurt, University of Bonn

References & Publications (5)

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. Epub 2007 Aug 29. — View 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. — View 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. — View Citation

Schmitt-Grohé 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. Epub 2005 Sep 23. — View Citation

Steinkamp G, Schmitt-Grohe S, Döring G, Staab D, Pfründer 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lipoproteins in Serum (after overnight fast)	VLDL,LDL,HDL, Cholesterin	Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Primary	Fatty acids in EDTA-Plasma and erythrocyte membranes (after overnight fast)	linol acid, arachidon acid, Alpha linolen acid, eicosapentaen acid, Docoshexaen acidsdocosahexaen acid	Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary	Cytokines in induced sputum and whole blood	Lipopolysaccharid binding Protein (LBP), interleukin-8 (IL-8) und Tumor necrosis factor Alpha (TNF Alpha)	Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary	ICAM1 (Serum)		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary	Matrixmetalloprotease 9 (Serum)		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary	WBC + CRP, IgE, RAST Aspergillus fum, ECP (Serum), Carotin, Vitamin E		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary	Shwachman-Score	Clinical score	Day 0
Secondary	Body weight, length		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary	Lung function test	VC, FEV1, MEF 25	Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary	Nutrition protocol	Evaluation of Food intake and calculation of fat composition, Protein etc.	For 7 days before day 0 and day 28
Secondary	Resolvins in EDTA plasma		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)