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

NCT ID: NCT00405665

Last Updated: 2013-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2009-06-30

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; L-Arginine; Pediatrics; pulmonary function

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

Group Type: EXPERIMENTAL

L-arginine

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

L-arginine

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

L-arginine

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Felix Ratjen

Division Head, Respiratory Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Felix Ratjen, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children, Toronto Canada

Locations

St. Michael's Hospital

Toronto, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

Canada

References

Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.

Reference Type: DERIVED

PMID: 37319354 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23333044 (View on PubMed)

Other Identifiers

1000009282

Identifier Type: -

Identifier Source: org_study_id