Anti-Inflammatory Pulmonal Therapy of CF-Patients With Amitriptyline and Placebo
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ClinicalTrials.gov Identifier: NCT00515229 |
Recruitment Status :
Completed
First Posted : August 13, 2007
Last Update Posted : August 13, 2007
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Condition or disease | Intervention/treatment | Phase |
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Cystic Fibrosis Infection Pseudomonas Aeruginosa | Drug: amitriptyline | Phase 2 |
Cystic fibrosis (CF), the most common autosomal recessive disorder at least in western countries, is caused by mutations of the cystic fibrosis transmembrane conductance regulator molecule (CFTR) and affects approximately 40 000 patients in Europe. Most, if not all, CF-patients develop a chronic pulmonary infection with Pseudomonas aeruginosa (P. aeruginosa). At present it is un-known why CF-patients are highly sensitive to P. aeruginosa infections and, most important, no curative treatment for cystic fibrosis is available.
Our data on CFTR-deficient mice demonstrate that the CFTR-molecule does not only function as a chloride-channel, but also as a transporter for sphingolipids, in particular sphingosine and sphingosine-1-phosphate. Deficiency of functional CFTR in CFTR-knock-out mice results in an alteration of the sphingolipid metabolism in pulmonary epithelial cells and an accumulation of cellular ceramide in these cells.
Inhibition of ceramide release in the lung was achieved by pharmacological and genetic inhibition of the acid sphingomyelinase (ASM) that generates ceramide from sphingomyelin. Amitriptyline was employed to pharmacologically block the ASM genetic inhibition of the ASM was achieved by crossing CFTR- and ASM-deficient mice. Although the ASM is not affected in cystic fibrosis, an inhibition of the enzyme should block the formation of ceramide and, thus, normalize the increase of pulmonary ceramide caused by CFTR-deficiency.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 18 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Protocol for a Phase II-Study Anti-Inflammatory Pulmonal Therapy of CF-Patients With Amitriptyline and Placebo - Randomised, Double-Blinded, Placebo-Controlled, Cross Over - Study - |
Study Start Date : | October 2006 |
Actual Study Completion Date : | July 2007 |

Arm | Intervention/treatment |
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Active Comparator: 1
Verum 1: Each individual capsule has a filling volume of 25 mg amitriptyline, given once an day in the evening over 28 days
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Drug: amitriptyline
Each individual capsule has a filling volume of 25 mg, 50 mg und 75 mg Amitriptyline. Placebo: 25 mg corn starch |
Active Comparator: 2
Verum 1: Each individual capsule has a filling volume of 50 mg amitriptyline, given once an day in the evening over 28 days
|
Drug: amitriptyline
Each individual capsule has a filling volume of 25 mg, 50 mg und 75 mg Amitriptyline. Placebo: 25 mg corn starch |
Active Comparator: 3
Verum 3: Each individual capsule has a filling volume of 75 mg amitriptyline, given once an day in the evening over 28 days
|
Drug: amitriptyline
Each individual capsule has a filling volume of 25 mg, 50 mg und 75 mg Amitriptyline. Placebo: 25 mg corn starch |
Placebo Comparator: 0
Placebo: Each individual capsule has a filling volume of 25 mg placebo (corn starch), given once an day in the evening over 28 days
|
Drug: amitriptyline
Each individual capsule has a filling volume of 25 mg, 50 mg und 75 mg Amitriptyline. Placebo: 25 mg corn starch |
- Increase in lung function, especially the FEV1 increase [ Time Frame: 5 months ]
- Increase of CO-Diffusion [ Time Frame: 5 months ]
- Pulmonary Ceramide expression [ Time Frame: 5 months ]
- Decrease of cytokine-concentrations [ Time Frame: 5 months ]
- Decrease of leukocytes (sputum) [ Time Frame: 5 months ]
- Decrease of Pseudomonas [ Time Frame: 5 months ]
- Infection parameters in serum [ Time Frame: 5 months ]
- Exacerbations [ Time Frame: 5 months ]

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Ages Eligible for Study: | 18 Years to 50 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Cystic Fibrosis is proved
- The patient are older than 18 years (<50 years)
- No sec discrimination
- The patient is pulmonal colonized with bacteria
- Signs of pulmonary exacerbation are not present
- A full course of therapy is possible without any restrictions
- Lung function measurement is possible
Exclusion Criteria:
- Poor metabolizer for amitriptyline (CYP2D6 genotyping)
- Glaucoma, seizures, heart insufficiency or depression is present
- Signs of acute pulmonary illness (bronchial or tracheal stenosis, tuberculosis, thorax trauma, acute pneumonia, pneumothorax, bronchial haemorrhage, ARDS) are present
- intravenous antibiotic treatment was necessary in the last 4 weeks
- Involvement of the patient in another study
- Pregnancy

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00515229
Germany | |
University of Tuebingen | |
Tuebingen, Baden-Wuerttemberg, Germany, 72076 |
Principal Investigator: | Joachim Reithmueller, Dr. | University of Tuebingen, Paediatric Department |
ClinicalTrials.gov Identifier: | NCT00515229 |
Other Study ID Numbers: |
APA-II |
First Posted: | August 13, 2007 Key Record Dates |
Last Update Posted: | August 13, 2007 |
Last Verified: | August 2007 |
cystic fibrosis ceramide amitriptyline Pseudomonas aeruginosa lung function |
Pseudomonas Infections Cystic Fibrosis Fibrosis Pathologic Processes Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Gram-Negative Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses Infections Amitriptyline |
Antidepressive Agents, Tricyclic Antidepressive Agents Psychotropic Drugs Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Adrenergic Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Adrenergic Agents Neurotransmitter Agents |