We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00405665
Recruitment Status : Completed
First Posted : November 30, 2006
Last Update Posted : September 2, 2013
Sponsor:
Information provided by (Responsible Party):
Felix Ratjen, The Hospital for Sick Children

Brief Summary:
The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of CF patients.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: L-arginine Phase 2

Detailed Description:
Despite the inflammatory nature of lung disease in CF, nitric oxide (NO) formation as well as the expression of NOS2 has been found to be decreased in CF airways. While the reasons for impaired airway NO formation remain incompletely understood, there is evidence that low NO formation contributes to lung pathophysiology in CF. Constitutive endogenous formation of Nitric oxide (NO) in airways is thought to play a role in neurotransmission, smooth muscle relaxation and bronchodilation. Previous animal experiments have shown that the addition of L-arginine, the precursor of enzymatic NO formation, resulted in a significantly greater relaxation of tracheas. There is also evidence that a single dose of inhaled L-arginine improves pulmonary function in CF. In this study we will assess the effect of L-arginine inhalation on lung function, nitric oxide formation, airway inflammation and bacterial infection in CF patients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Pilot Study of the Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
Study Start Date : November 2006
Actual Primary Completion Date : June 2009
Actual Study Completion Date : June 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: 1 Drug: L-arginine
Group 1 will receive the active treatment followed by the inactive treatment. The active treatment phase will consist of L-arginine 250 mg/ml dispensed in 2.2 ml vials, from which the patient will take 2ml (500mg) and dilute with 3ml of sterile water to give 5ml of a 100mg/ml solution. Dosing in the inactive treatment phase will consist of a placebo of similar osmolarity and appearance will be formulated and dosed in a similar fashion. It will consist of 2.2ml vials of 1110mmol/L hypertonic saline. Again, the patient will take 2ml and dilute with 3ml of sterile water to give a 445mmol/L solution which has similar tonicity (10%) to the L-arginine. Both treatment phases will be administered by inhalation with a PARI eFLOW device.

Experimental: 2 Drug: L-arginine
Group 2 will receive the inactive treatment followed by the active treatment.




Primary Outcome Measures :
  1. Change in FEV1 (in liters) from baseline [ Time Frame: At the end of the 14 day treatment period ]
  2. Adverse events such as gastrointestinal complaints, wheezing, hepatitis or shortness of breath [ Time Frame: 70 weeks ]

Secondary Outcome Measures :
  1. Change in FVC and change in FEV25-75 from baseline to completion of the 2 week treatment period. [ Time Frame: Will be measured at the end of the 14 day treatment period ]
  2. Change in exhaled nitric oxide (FeNO) [ Time Frame: 70 days ]
  3. Changes in inflammatory markers in sputum from baseline including neutrophils (sputum), neutrophil elastase (sputum) and interleukin (IL)-8 concentrations (sputum). [ Time Frame: Will me measured at the end of the 14 day treatment period ]
  4. Changes in sputum concentrations of L-arginine metabolites [ Time Frame: 70 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride concentration > 60 mEq/L and/or two well characterized disease causing CFTR gene mutations
  • 14 years of age and older at enrollment
  • Clinically stable at enrollment
  • Ability to comply with medication use, study visits and study procedures
  • FEV1 % predicted > 40% < 80 % as calculated by reference equations

Exclusion Criteria:

  • Respiratory culture positive for: B. cepacia complex within past year or at screening
  • Use of systemic corticosteroids within 30 days of screening
  • Use of intravenous antibiotics or oral quinolones within 14 days of screening
  • History of biliary cirrhosis, portal hypertension, or splenomegaly
  • Other major organ dysfunction
  • History of lung transplantation or currently on lung transplant list
  • Supplemental oxygen therapy
  • Oxygen saturation < 95 % on room air
  • Positive pregnancy test at screening
  • Investigational drug use within 30 days of screening
  • History of alcohol, illicit drug or medication abuse within 1 year of screening
  • Acute respiratory symptoms
  • Inability to take any form of bronchodilator
  • Wheezing at the time of study

Information from the National Library of Medicine

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): NCT00405665


Locations
Layout table for location information
Canada, Ontario
St. Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Layout table for investigator information
Principal Investigator: Felix Ratjen, MD The Hospital for Sick Children, Toronto Canada
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Felix Ratjen, Division Head, Respiratory Medicine, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00405665    
Other Study ID Numbers: 1000009282
First Posted: November 30, 2006    Key Record Dates
Last Update Posted: September 2, 2013
Last Verified: August 2013
Keywords provided by Felix Ratjen, The Hospital for Sick Children:
Cystic Fibrosis
L-Arginine
Pediatrics
pulmonary function
Additional relevant MeSH terms:
Layout table for MeSH terms
Cystic Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases