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| Name | Class |
|---|---|
| University of Bonn | OTHER |
| Goethe University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Azithromycin | Experimental | oral Azithromycin 10 mg/kg Body weight, max. 500 mg every Monday, Wednesday and Friday for 4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azithromycin | Drug |
|
|
| 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) |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sabina Schmitt-Grohé, MD | University Children's Hospital | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14762183 | Background | 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. | |
| 18701270 | Background | 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. |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D017963 | Azithromycin |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
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CF patients receive for 4 weeks Azithromycin. Study measures are assessed before and after 4 weeks
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| 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) |
| 16183806 | Background | 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. |
| 17761616 | Background | 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. |
| 19503797 | Background | 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. |
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| Organic Chemicals |