Cystic Fibrosis
Conditions
Keywords
Inhaled Nitric oxide, Cystic Fibrosis
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.
Interventions
DRUGNitrogen
100% nitrogen (placebo) will be administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
Nitric oxide will be administered at 20 ppm via nasal cannula over a 44 hour period.
Sponsors
Mallinckrodt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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%. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Nitric Oxide Low Dose Low dose group received Inhaled Nitric Oxide at 20 parts per million (ppm) via nasal cannula for 44 hours | 6 |
| Inhaled Nitric Oxide High Dose High dose group received Inhaled Nitric Oxide at 40 ppm via nasal cannula for 44 hours. | 6 |
| Nitrogen Nitrogen (Placebo) administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Inhaled Nitric Oxide High Dose | Nitrogen | Inhaled Nitric Oxide Low Dose | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 3 Participants | 5 Participants | 13 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Age, Continuous | 15.6 years STANDARD_DEVIATION 2.33 | 17.7 years STANDARD_DEVIATION 5.14 | 16.9 years STANDARD_DEVIATION 2.14 | 16.7 years STANDARD_DEVIATION 3.4 |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 18 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 4 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 1 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: Baseline and 48 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Nitric Oxide Low Dose | Change in Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second at Baseline | 3.4 Liters | Standard Deviation 0.66 |
| Inhaled Nitric Oxide Low Dose | Change in Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second at 48 hours | 3.5 Liters | Standard Deviation 0.66 |
| Inhaled Nitric Oxide High Dose | Change in Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second at Baseline | 3.1 Liters | Standard Deviation 1.07 |
| Inhaled Nitric Oxide High Dose | Change in Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second at 48 hours | 3.1 Liters | Standard Deviation 1.17 |
| Nitrogen | Change in Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second at Baseline | 3.0 Liters | Standard Deviation 0.85 |
| Nitrogen | Change in Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second at 48 hours | 3.0 Liters | Standard Deviation 0.83 |
Primary
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%
Time frame: Baseline and 48 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Nitric Oxide Low Dose | Change in Oxygen Saturation | Oxygen Saturation at Baseline | 95.5 Percent of oxygen saturation | Standard Deviation 1.87 |
| Inhaled Nitric Oxide Low Dose | Change in Oxygen Saturation | Oxygen Saturation at 48 hours | 95.7 Percent of oxygen saturation | Standard Deviation 2.16 |
| Inhaled Nitric Oxide High Dose | Change in Oxygen Saturation | Oxygen Saturation at Baseline | 94.8 Percent of oxygen saturation | Standard Deviation 2.14 |
| Inhaled Nitric Oxide High Dose | Change in Oxygen Saturation | Oxygen Saturation at 48 hours | 95.8 Percent of oxygen saturation | Standard Deviation 3.19 |
| Nitrogen | Change in Oxygen Saturation | Oxygen Saturation at Baseline | 95.5 Percent of oxygen saturation | Standard Deviation 2.66 |
| Nitrogen | Change in Oxygen Saturation | Oxygen Saturation at 48 hours | 97.0 Percent of oxygen saturation | Standard Deviation 1.1 |
Primary
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%.
Time frame: Baseline and 48 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Inhaled Nitric Oxide Low Dose | Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels | Methemoglobin Levels at Baseline | 0.4 Percent of Methemoglobin Level | Standard Deviation 0.14 |
| Inhaled Nitric Oxide Low Dose | Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels | Methemoglobin Levels at 48 hours | 0.3 Percent of Methemoglobin Level | Standard Deviation 0.14 |
| Inhaled Nitric Oxide High Dose | Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels | Methemoglobin Levels at Baseline | 0.5 Percent of Methemoglobin Level | Standard Deviation 0.48 |
| Inhaled Nitric Oxide High Dose | Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels | Methemoglobin Levels at 48 hours | 0.1 Percent of Methemoglobin Level | Standard Deviation 0.1 |
| Nitrogen | Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels | Methemoglobin Levels at Baseline | 0.3 Percent of Methemoglobin Level | Standard Deviation 0.19 |
| Nitrogen | Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels | Methemoglobin Levels at 48 hours | 0.4 Percent of Methemoglobin Level | Standard Deviation 0.21 |