Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Cystic Fibrosis |
Drug: Nitric Oxide for Inhalation Drug: Nitrogen |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis |
- Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels [ Time Frame: Baseline and 48 hours ] [ Designated as safety issue: Yes ]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 [ Time Frame: Baseline and 48 hours ] [ Designated as safety issue: Yes ]
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) [ Time Frame: Baseline and 48 hours ] [ Designated as safety issue: No ]Decrease in forced expiratory volume in 1 second was measured through spirometer. Spirometer measures the volume of air inspired and expired by the lungs.
- Assess the Difference in Sputum Bacterial Density Before and After NO Inhalation. Assess the Difference in Lower Airway Inflammatory Measures Before and After NO Inhalation [ Time Frame: 44 hours ] [ Designated as safety issue: Yes ]
| Enrollment: | 18 |
| Study Start Date: | July 2004 |
| Study Completion Date: | December 2008 |
| Primary Completion Date: | December 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Low Dose Cohort
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
Nitric oxide will be administered at 20 ppm via nasal cannula over a 44 hour period.
Other Name: INO
|
|
Experimental: High-Dose Cohort
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
Nitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period.
Other Name: INO
|
|
Placebo Comparator: Nitrogen
100% Nitrogen (placebo) will be administer at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
|
Drug: Nitrogen
100% nitrogen (placebo) will be administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
Other Name: Nitrogen (N2) Grade 5
|
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.
Eligibility| Ages Eligible for Study: | 12 Years and older |
| Genders Eligible for Study: | Both |
| Accepts 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.
Contacts and Locations More Information
No publications provided
| Responsible Party: | James Baldassare, MD, INO Therapeutics |
| ClinicalTrials.gov Identifier: | NCT00570349 History of Changes |
| Other Study ID Numbers: | INOT 50 |
| Study First Received: | December 6, 2007 |
| Results First Received: | October 1, 2010 |
| Last Updated: | November 30, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by INO Therapeutics:
|
Inhaled Nitric oxide Cystic Fibrosis |
Additional relevant MeSH terms:
|
Cystic Fibrosis Fibrosis Pancreatic Diseases Digestive System Diseases Lung Diseases Respiratory Tract Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Pathologic Processes Nitric Oxide Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Pharmacologic Actions Anti-Asthmatic Agents Respiratory System Agents Therapeutic Uses Free Radical Scavengers Antioxidants Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Endothelium-Dependent Relaxing Factors Vasodilator Agents Cardiovascular Agents Protective Agents |
ClinicalTrials.gov processed this record on May 22, 2013