Effect of Azithromycin on Fatty Acids in CF

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

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.

Study Overview

• Status: Unknown
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Azithromycin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 60 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Azithromycin; oral Azithromycin 10 mg/kg Body weight, max. 500 mg every Monday, Wednesday and Friday for 4 weeks	Drug: Azithromycin; Other Names: Zithromax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipoproteins in Serum (after overnight fast)	VLDL,LDL,HDL, Cholesterin	Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
ICAM1 (Serum)		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Matrixmetalloprotease 9 (Serum)		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
WBC + CRP, IgE, RAST Aspergillus fum, ECP (Serum), Carotin, Vitamin E		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Shwachman-Score	Clinical score	Day 0
Body weight, length		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Lung function test	VC, FEV1, MEF 25	Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Nutrition protocol	Evaluation of Food intake and calculation of fat composition, Protein etc.	For 7 days before day 0 and day 28
Resolvins in EDTA plasma		Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)

Collaborators and Investigators

• Sponsor: University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)
• Collaborators: University of Bonn; University Hospital Frankfurt
• Investigators: Principal Investigator: Sabina Schmitt-Grohé, MD, University Children's Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ANTICIPATED): December 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: February 2, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (ESTIMATE): February 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 2, 2018
• Last Update Submitted That Met QC Criteria: July 31, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: cystic fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: Sylvia 253/12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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