Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis

Phase 1

Completed

Brief Summary: The primary objective of the trial is to assess the safety and tolerability of inhaled nitric oxide (NO) when administered by nasal cannula over a 44 hour period to clinically stable Cystic Fibrosis (CF) subjects. Toxicity is to be defined as a drop in oxygen saturations, a decline in forced expiratory volume in one second (FEV1), or an increase in methemoglobin.

Detailed Description: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A cycle of chronic, persistent infections with CF-related pathogens and an excessive inflammatory response progressively damages the airways and lung parenchyma, resulting in widespread bronchiectasis and ultimately, respiratory failure. Despite tremendous advances in understanding the CF gene and the CFTR protein, it is not known exactly how mutations in the gene and defects in CFTR lead to persistent airway infection and inflammation.

Inhaled nitric oxide (NO) has potential to be an effective treatment in CF lung disease. Inhaled NO has been studied in other airways diseases characterized by infection and /or inflammation such as COPD and idiopathic pulmonary fibrosis.

NO has been shown to activate CFTR and alternative chloride channels, thereby increasing chloride current in epithelial cells. Therefore, NO treatment may be beneficial in individuals with CF.

Recruitment & Eligibility

Inclusion Criteria

Confirmed diagnosis of CF
12 years of age and older
FEV1 greater than 40% of predicted
Resting awake oxygen saturation of at least 88%
Stable pulmonary disease as defined by both clinical impression and having had no recent hospitalizations or changes in antibiotic regimen within 1 month prior to enrollment
Signed informed consent form

Exclusion Criteria

Pulmonary exacerbation resulting in antibiotic treatment (except prophylactic antibiotics) within 1 month of enrollment
Isolation of B. cepacia from a respiratory tract culture within 6 months
Severe nasal obstruction at the time of screening
Receipt of any aerosolized experimental or investigational drugs within 1 month of enrollment
Pregnancy (a negative pregnancy test must be documented prior to enrollment if applicable)
Patients who have received treatment with nitric oxide for inhalation within 24 hours prior to study initiation or other investigational medications within 24 hours.

Arm && Interventions

Group	Intervention	Description
Nitrogen	Nitrogen	100% Nitrogen (placebo) will be administer at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
Low Dose Cohort	Nitric Oxide for Inhalation	Subjects in the low dose cohort receive 20 part per million (ppm) of nitric oxide via nasal cannula over a 44 hour period.
High-Dose Cohort	Nitric Oxide for Inhalation	Subjects in the high dose cohort receive 40 ppm of nitric oxide via nasal cannula over a 44 hour period.

Primary Outcome Measures

Name	Time	Method
Change in Oxygen Saturation	Baseline and 48 hours	Safety and tolerability of drug assessed by decreased oxygen saturation was measured through pulse oximeter, which measure the amount of oxygen in the blood. Normal range percentage is 95 - 100%
Change in Forced Expiratory Volume in 1 Second (FEV1)	Baseline and 48 hours	Decrease in forced expiratory volume in 1 second was measured through spirometer. Spirometer measures the volume of air inspired and expired by the lungs.
Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels	Baseline and 48 hours	Methemoglobin level assessments were measured through blood draws - hematology. This test measures the amount of methemoglobin (a type of hemoglobin that is unable to transport oxygen to tissues) in blood. Normal methemoglobin percentage range 1% - 2%.