Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline
Background/Aims: Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF). Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2016-07-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/445648 |
| _version_ | 1819107248527376384 |
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| author | Constantin Adams Vanya Icheva Caroline Deppisch Josefine Lauer Gloria Herrmann Ute Graepler-Mainka Susanne Heyder Erich Gulbins Joachim Riethmueller |
| author_facet | Constantin Adams Vanya Icheva Caroline Deppisch Josefine Lauer Gloria Herrmann Ute Graepler-Mainka Susanne Heyder Erich Gulbins Joachim Riethmueller |
| author_sort | Constantin Adams |
| collection | DOAJ |
| description | Background/Aims: Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF). Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a benefit in lung function, weight and exacerbation rates. Methods: To test for a beneficial effect of amitriptyline in vivo, we performed two phase II randomised, double-blind, placebo-controlled studies. CF patients were treated with 25 mg amitriptyline twice daily, i.e. a total dose of 50 mg/d. After those two studies part of the patients used amitriptyline in an off-lable-use for routine treatment. These patients were observed after one, two and three years after continuous use of amitriptyline and were matched with those patients who were not treated. These patients were used as a control group. Results: After one year of treatment, forced expiratory volume in 1 sec predicted (FEV1) increased significantly by 7.6±7.0%, p=1 decreased significantly in the control group by 1.8±3.3%, p=0.010, and weight increased by 1.1±2.7kg, p=0.010 (n=14). After two years of treatment, FEV1 increased significantly by 5.6±10.3%, p=0.009, and weight increased by 3.6±2.9kg, p=1 decreased in the control group by 2.1±3.7%, p=0.051 and weight increased by only 0.4±2.9kg, p=0.31 (n=10). After three years of treatment, FEV1 increased significantly by 7.7±8%, p=0.050, and weight increased by 7.3±3.8kg, p=0.016, in the amitriptyline population (n=5), whereas FEV1 decreased in the control group by 1.0±1.3%, p=0.075 and weight increased by 0.4±1.5kg, p=0.29 (n=5). Conclusion: Amitriptyline significantly increases FEV1, reduces ceramide in lung cells and increases weight of CF patients. |
| first_indexed | 2024-12-22T02:51:01Z |
| format | Article |
| id | doaj.art-64f2a352f97845b7b0d3eac0b2c68020 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-22T02:51:01Z |
| publishDate | 2016-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-64f2a352f97845b7b0d3eac0b2c680202022-12-21T18:41:23ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-07-0139256557210.1159/000445648445648Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with AmitriptylineConstantin AdamsVanya IchevaCaroline DeppischJosefine LauerGloria HerrmannUte Graepler-MainkaSusanne HeyderErich GulbinsJoachim RiethmuellerBackground/Aims: Several recent clinical studies revealed an accumulation of ceramide in bronchial epithelial cells of patients with cystic fibrosis (CF). Degradation of ceramide concentrations in lungs of CF patients employing the functional acid sphingomyelinase inhibitor amitriptyline revealed a benefit in lung function, weight and exacerbation rates. Methods: To test for a beneficial effect of amitriptyline in vivo, we performed two phase II randomised, double-blind, placebo-controlled studies. CF patients were treated with 25 mg amitriptyline twice daily, i.e. a total dose of 50 mg/d. After those two studies part of the patients used amitriptyline in an off-lable-use for routine treatment. These patients were observed after one, two and three years after continuous use of amitriptyline and were matched with those patients who were not treated. These patients were used as a control group. Results: After one year of treatment, forced expiratory volume in 1 sec predicted (FEV1) increased significantly by 7.6±7.0%, p=1 decreased significantly in the control group by 1.8±3.3%, p=0.010, and weight increased by 1.1±2.7kg, p=0.010 (n=14). After two years of treatment, FEV1 increased significantly by 5.6±10.3%, p=0.009, and weight increased by 3.6±2.9kg, p=1 decreased in the control group by 2.1±3.7%, p=0.051 and weight increased by only 0.4±2.9kg, p=0.31 (n=10). After three years of treatment, FEV1 increased significantly by 7.7±8%, p=0.050, and weight increased by 7.3±3.8kg, p=0.016, in the amitriptyline population (n=5), whereas FEV1 decreased in the control group by 1.0±1.3%, p=0.075 and weight increased by 0.4±1.5kg, p=0.29 (n=5). Conclusion: Amitriptyline significantly increases FEV1, reduces ceramide in lung cells and increases weight of CF patients.http://www.karger.com/Article/FullText/445648Cystic FibrosisAmitriptylineCeramideCFTR |
| spellingShingle | Constantin Adams Vanya Icheva Caroline Deppisch Josefine Lauer Gloria Herrmann Ute Graepler-Mainka Susanne Heyder Erich Gulbins Joachim Riethmueller Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline Cellular Physiology and Biochemistry Cystic Fibrosis Amitriptyline Ceramide CFTR |
| title | Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline |
| title_full | Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline |
| title_fullStr | Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline |
| title_full_unstemmed | Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline |
| title_short | Long-Term Pulmonal Therapy of Cystic Fibrosis-Patients with Amitriptyline |
| title_sort | long term pulmonal therapy of cystic fibrosis patients with amitriptyline |
| topic | Cystic Fibrosis Amitriptyline Ceramide CFTR |
| url | http://www.karger.com/Article/FullText/445648 |
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