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

NCT00405665 | Completed Phase 2

• 1 other identifier: 1000009282
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; L-Arginine; Pediatrics; pulmonary function

Outcome Measures

Primary Outcomes (2)

• Change in FEV1 (in liters) from baseline

  At the end of the 14 day treatment period

• Adverse events such as gastrointestinal complaints, wheezing, hepatitis or shortness of breath

  70 weeks

Secondary Outcomes (4)

• 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

• Change in exhaled nitric oxide (FeNO)

  70 days

• 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

• Changes in sputum concentrations of L-arginine metabolites

  70 days

Study Arms (2)

1

EXPERIMENTAL

Drug: L-arginine

2

EXPERIMENTAL

Drug: L-arginine

Interventions

L-arginine 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.

1

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Hospital for Sick Children: lead

Study Sites (2)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (2)

• 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.

  PMID: 37319354 DERIVED

• 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.

  PMID: 23333044 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Arginine

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Felix Ratjen, MD

  The Hospital for Sick Children, Toronto Canada

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Head, Respiratory Medicine

Study Record Dates

• First Submitted: November 28, 2006
• First Posted: November 30, 2006
• Study Start: November 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: September 2, 2013

Record last verified: 2013-08

Locations

CA (2)