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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00570349
• Other study ID #: INOT 50
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 2004
• Est. completion date: December 2008

Study information

• Verified date: May 2016
• Source: Mallinckrodt
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

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.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Nitric Oxide for Inhalation
Nitric oxide will be administered at 20 ppm via nasal cannula over a 44 hour period.
• Nitric Oxide for Inhalation
Nitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period.
• Nitrogen
100% nitrogen (placebo) will be administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.

Locations

Country	Name	City	State
United States	The Children's Hospital	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Mallinckrodt

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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%.	Baseline and 48 hours
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%	Baseline and 48 hours
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.	Baseline and 48 hours