Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nitric Oxide for Inhalation
Nitric Oxide for Inhalation
Nitrogen
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis focused on measuring Inhaled Nitric oxide, Cystic Fibrosis
Eligibility Criteria
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.
Sites / Locations
- The Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Low Dose Cohort
High-Dose Cohort
Nitrogen
Arm Description
Subjects in the low dose cohort receive 20 part per million (ppm) of nitric oxide via nasal cannula over a 44 hour period.
Subjects in the high dose cohort receive 40 ppm of nitric oxide via nasal cannula over a 44 hour period.
100% Nitrogen (placebo) will be administer at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
Outcomes
Primary Outcome Measures
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%.
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%
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00570349
Brief Title
Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis
Official Title
Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mallinckrodt
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
Inhaled Nitric oxide, Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low Dose Cohort
Arm Type
Experimental
Arm Description
Subjects in the low dose cohort receive 20 part per million (ppm) of nitric oxide via nasal cannula over a 44 hour period.
Arm Title
High-Dose Cohort
Arm Type
Experimental
Arm Description
Subjects in the high dose cohort receive 40 ppm of nitric oxide via nasal cannula over a 44 hour period.
Arm Title
Nitrogen
Arm Type
Placebo Comparator
Arm Description
100% Nitrogen (placebo) will be administer at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
Intervention Type
Drug
Intervention Name(s)
Nitric Oxide for Inhalation
Other Intervention Name(s)
INO
Intervention Description
Nitric oxide will be administered at 20 ppm via nasal cannula over a 44 hour period.
Intervention Type
Drug
Intervention Name(s)
Nitric Oxide for Inhalation
Other Intervention Name(s)
INO
Intervention Description
Nitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period.
Intervention Type
Drug
Intervention Name(s)
Nitrogen
Other Intervention Name(s)
Nitrogen (N2) Grade 5
Intervention Description
100% nitrogen (placebo) will be administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
Primary Outcome Measure Information:
Title
Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels
Description
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
Title
Change in Oxygen Saturation
Description
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
Title
Change in Forced Expiratory Volume in 1 Second (FEV1)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Sagel, MD
Organizational Affiliation
The Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Children's Hospital
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis
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