Clinical trial NCT03045198: 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
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
Lead sponsor: University Childrens' Hospital (Zentrum für Kinderheilkunde des Universitätsklinikum Bonn)
Sponsor class: OTHER
Collaborators: name: University of Bonn
name: Goethe University
First posted: 2017-02-07
Enrollment: 20
Sex: ALL
Minimum age (years): 10
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: CF patients receive for 4 weeks Azithromycin. Study measures are assessed before and after 4 weeks
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Lipoproteins in Serum (after overnight fast)
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
measure: Fatty acids in EDTA-Plasma and erythrocyte membranes (after overnight fast)
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Secondary outcomes:
measure: Cytokines in induced sputum and whole blood
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
measure: ICAM1 (Serum)
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
measure: Matrixmetalloprotease 9 (Serum)
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
measure: WBC + CRP, IgE, RAST Aspergillus fum, ECP (Serum), Carotin, Vitamin E
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
measure: Shwachman-Score
timeFrame: Day 0
measure: Body weight, length
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
measure: Lung function test
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
measure: Nutrition protocol
timeFrame: For 7 days before day 0 and day 28
measure: Resolvins in EDTA plasma
timeFrame: Day 0 (before azithromycin), Day 28 (day 28 of azithromycin treatment)
Other outcomes:
Locations:
Study officials:
affiliation: University Children's Hospital
name: Sabina Schmitt-Grohé, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.