NCT00515229

Brief Summary

Our data indicate that the CFTR-molecule functions as a transporter for sphingosine-1-phosphate and sphingosine or regulates the uptake of these sphingolipids by epithelial cells. The disturbed uptake of sphingosine and sphingosine-1-phosphate over the cell membrane results in an accumulation of ceramide in the cell membrane, which finally triggers a pro-inflammatory and pro-apoptotic status in the respiratory tract of cystic fibrosis patients. Amitriptyline reduces the cera-mide levels in the lung tissue, normalises the activity of cytokines and prevents constitutive cell death of epithelial cells observed in CFTR-deficient mice. Most important, amitriptyline prevents pulmonary infections of CFTR-deficient mice with P. aeruginosa. These effects of amitriptyline may result in an improved lung function of cystic fibrosis patients.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Oct 2006

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2006

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2007

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

August 9, 2007

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 13, 2007

Completed
Last Updated

August 13, 2007

Status Verified

August 1, 2007

First QC Date

August 9, 2007

Last Update Submit

August 10, 2007

Conditions

Cystic FibrosisInfectionPseudomonas Aeruginosa

Keywords

cystic fibrosisceramideamitriptylinePseudomonas aeruginosalung function

Outcome Measures

Primary Outcomes (1)

  • Increase in lung function, especially the FEV1 increase

    5 months

Secondary Outcomes (7)

  • Increase of CO-Diffusion

    5 months

  • Pulmonary Ceramide expression

    5 months

  • Decrease of cytokine-concentrations

    5 months

  • Decrease of leukocytes (sputum)

    5 months

  • Decrease of Pseudomonas

    5 months

  • +2 more secondary outcomes

Study Arms (4)

1

ACTIVE COMPARATOR

Verum 1: Each individual capsule has a filling volume of 25 mg amitriptyline, given once an day in the evening over 28 days

Drug: amitriptyline

2

ACTIVE COMPARATOR

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

3

ACTIVE COMPARATOR

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

0

PLACEBO COMPARATOR

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

Interventions

amitriptylineDRUG

Each individual capsule has a filling volume of 25 mg, 50 mg und 75 mg Amitriptyline. Placebo: 25 mg corn starch

0123

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Related Publications (1)

  • Becker KA, Riethmuller J, Luth A, Doring G, Kleuser B, Gulbins E. Acid sphingomyelinase inhibitors normalize pulmonary ceramide and inflammation in cystic fibrosis. Am J Respir Cell Mol Biol. 2010 Jun;42(6):716-24. doi: 10.1165/rcmb.2009-0174OC. Epub 2009 Jul 27.

    PMID: 19635928DERIVED

MeSH Terms

Conditions

Cystic FibrosisInfectionsPseudomonas Infections

Interventions

Amitriptyline

Condition Hierarchy (Ancestors)

Pancreatic DiseasesDigestive System DiseasesLung DiseasesRespiratory Tract DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesInfant, Newborn, DiseasesGram-Negative Bacterial InfectionsBacterial InfectionsBacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

DibenzocycloheptenesBenzocycloheptenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Joachim Reithmueller, Dr.

    University of Tuebingen, Paediatric Department

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER

Study Record Dates

First Submitted

August 9, 2007

First Posted

August 13, 2007

Study Start

October 1, 2006

Study Completion

July 1, 2007

Last Updated

August 13, 2007

Record last verified: 2007-08

Locations

DE(1)