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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Nitric Oxide for Inhalation
* Drug: Nitric Oxide for Inhalation
* Drug: Nitrogen


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Cohort<br>Subjects in the low dose cohort receive 20 part per million (ppm) of nitric oxide via nasal cannula over a 44 hour period. | Drug: Nitric Oxide for Inhalation<br>* Nitric oxide will be administered at 20 ppm via nasal cannula over a 44 hour period.<br>* Other names: INO;|
| Experimental: High-Dose Cohort<br>Subjects in the high dose cohort receive 40 ppm of nitric oxide via nasal cannula over a 44 hour period. | Drug: Nitric Oxide for Inhalation<br>* Nitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period.<br>* Other names: INO;|
| Placebo Comparator: Nitrogen<br>100% Nitrogen (placebo) will be administer at 20 ppm or 40 ppm via nasal cannula over a 44 hour period. | Drug: Nitrogen<br>* 100% nitrogen (placebo) will be administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.<br>* Other names: Nitrogen (N2) Grade 5;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels | 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%. | Baseline and 48 hours | 
| Change in Oxygen Saturation | 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% | Baseline and 48 hours | 
| Change in Forced Expiratory Volume in 1 Second (FEV1) | Decrease in forced expiratory volume in 1 second was measured through spirometer. Spirometer measures the volume of air inspired and expired by the lungs. | Baseline and 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inhaled Nitric oxide, Cystic Fibrosis