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

Cystic Fibrosis Clinical Trial

Official title:

Pilot Study of the Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00405665
• Other study ID #: 1000009282
• Status: Completed
• Phase: Phase 2
• First received: November 28, 2006
• Last updated: August 30, 2013
• Start date: November 2006
• Est. completion date: June 2009

Study information

• Verified date: August 2013
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

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.
• L-arginine
Group 2 will receive the inactive treatment followed by the active treatment.

Locations

Country	Name	City	State
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FEV1 (in liters) from baseline		At the end of the 14 day treatment period	No
Primary	Adverse events such as gastrointestinal complaints, wheezing, hepatitis or shortness of breath		70 weeks	Yes
Secondary	Change in FVC and change in FEV25-75 from baseline to completion of the 2 week treatment period.		Will be measured at the end of the 14 day treatment period	No
Secondary	Change in exhaled nitric oxide (FeNO)		70 days	No
Secondary	Changes in inflammatory markers in sputum from baseline including neutrophils (sputum), neutrophil elastase (sputum) and interleukin (IL)-8 concentrations (sputum).		Will me measured at the end of the 14 day treatment period	No
Secondary	Changes in sputum concentrations of L-arginine metabolites		70 days	No