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

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

L-arginine

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring Cystic Fibrosis, L-Arginine, Pediatrics, pulmonary function

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

St. Michael's Hospital
The Hospital for Sick Children

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

Change in FEV1 (in liters) from baseline

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

Secondary Outcome Measures

Change in FVC and change in FEV25-75 from baseline to completion of the 2 week treatment period.

Change in exhaled nitric oxide (FeNO)

Changes in inflammatory markers in sputum from baseline including neutrophils (sputum), neutrophil elastase (sputum) and interleukin (IL)-8 concentrations (sputum).

Changes in sputum concentrations of L-arginine metabolites

Full Information

NCT ID

NCT00405665

First Posted

November 28, 2006

Last Updated

August 30, 2013

Sponsor

The Hospital for Sick Children

1. Study Identification

Unique Protocol Identification Number

NCT00405665

Brief Title

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

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Completed

Study Start Date

November 2006 (undefined)

Primary Completion Date

June 2009 (Actual)

Study Completion Date

June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The Hospital for Sick Children

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

Keywords

Cystic Fibrosis, L-Arginine, Pediatrics, pulmonary function

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

L-arginine

Intervention Description

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

Intervention Name(s)

L-arginine

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in FEV1 (in liters) from baseline

Time Frame

At the end of the 14 day treatment period

Title

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

Time Frame

70 weeks

Secondary Outcome Measure Information:

Title

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

Title

Change in exhaled nitric oxide (FeNO)

Time Frame

70 days

Title

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

Title

Changes in sputum concentrations of L-arginine metabolites

Time Frame

70 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Felix Ratjen, MD

Organizational Affiliation

The Hospital for Sick Children, Toronto Canada

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Michael's Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5B 1W8

Country

Canada

Facility Name

The Hospital for Sick Children

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X8

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

23333044

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.

Results Reference

derived

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

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