Clinical trial NCT00405665: The Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
Official title: Pilot Study of the Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
L-Arginine
Pediatrics
pulmonary function
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2006-11-30
Enrollment: 20
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Change in FEV1 (in liters) from baseline
timeFrame: At the end of the 14 day treatment period
measure: Adverse events such as gastrointestinal complaints, wheezing, hepatitis or shortness of breath
timeFrame: 70 weeks
Secondary outcomes:
measure: Change in FVC and change in FEV25-75 from baseline to completion of the 2 week treatment period.
timeFrame: Will be measured at the end of the 14 day treatment period
measure: Change in exhaled nitric oxide (FeNO)
timeFrame: 70 days
measure: Changes in inflammatory markers in sputum from baseline including neutrophils (sputum), neutrophil elastase (sputum) and interleukin (IL)-8 concentrations (sputum).
timeFrame: Will me measured at the end of the 14 day treatment period
measure: Changes in sputum concentrations of L-arginine metabolites
timeFrame: 70 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children, Toronto Canada
name: Felix Ratjen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Grasemann H, Tullis E, Ratjen F. A randomized controlled trial of inhaled L-arginine in patients with cystic fibrosis. J Cyst Fibros. 2013 Sep;12(5):468-74. doi: 10.1016/j.jcf.2012.12.008. Epub 2013 Jan 14.