The Short Term Safety and Efficacy of Inhaled L-Arginine in Patients With Cystic Fibrosis - Full Text View

Sponsors and Collaborators:	The Hospital for Sick Children Irvin Foundation
Information provided by:	The Hospital for Sick Children
ClinicalTrials.gov Identifier:	NCT00405665

Purpose

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	Intervention	Phase
Cystic Fibrosis	Drug: L-arginine	Phase II

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Sodium chloride Arginine Arginine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Pilot Study of the Short Term Safety and Efficacy of Inhaled L-Arginine in Patients With Cystic Fibrosis

Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:

Change in FEV1 (in liters) from baseline [ Time Frame: At the end of the 14 day treatment period ] [ Designated as safety issue: No ]
Adverse events such as gastrointestinal complaints, wheezing, hepatitis or shortness of breath [ Time Frame: 70 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
Change in exhaled nitric oxide (FeNO) [ Time Frame: 70 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Changes in sputum concentrations of L-arginine metabolites [ Time Frame: 70 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	November 2006
Estimated Study Completion Date:	May 2009
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

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

Arms

Assigned Interventions

1: Experimental

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.

2: Experimental

Drug: L-arginine

Group 2 will receive the inactive treatment followed by the active treatment.

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.

Eligibility

Ages Eligible for Study:	14 Years and older
Genders Eligible for Study:	Both
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00405665

Contacts

Contact: Shawn Kerrigan, Coordinator

416-813-7654 ext 2016

shawn.kerrigan@sickkids.ca

Locations

Canada, Ontario
The Hospital for Sick Children	Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Felix Ratjen, MD 416 813 6167 felix.ratjen@sickkids.ca
Principal Investigator: Felix Ratjen, MD
Sub-Investigator: Hartmut Grasemann, MD
St. Michael's Hospital	Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: Elizabeth Tullis, MD 416-864-5406 tullise@smh.toronto.on.ca
Principal Investigator: Elizabeth Tullis, MD

Sponsors and Collaborators

The Hospital for Sick Children

Irvin Foundation

Investigators

Principal Investigator:

Felix Ratjen, MD

The Hospital for Sick Children, Toronto Canada

More Information

Responsible Party:	The Hospital for Sick Children ( Felix Ratjen/Principal Investigator )
Study ID Numbers:	1000009282
Study First Received:	November 28, 2006
Last Updated:	September 12, 2008
ClinicalTrials.gov Identifier:	NCT00405665
Health Authority:	Canada: Health Canada

Keywords provided by The Hospital for Sick Children:

Cystic Fibrosis
L-Arginine
Pediatrics
pulmonary function

Study placed in the following topic categories:

Digestive System Diseases
Genetic Diseases, Inborn
Respiratory Tract Diseases
Cystic Fibrosis
Fibrosis

Lung Diseases
Infant, Newborn, Diseases
Pancreatic Diseases
Cystic fibrosis

Additional relevant MeSH terms:

Pathologic Processes

ClinicalTrials.gov processed this record on January 14, 2009