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

This study has been completed.
Sponsor:
Information provided by:
INO Therapeutics
ClinicalTrials.gov Identifier:
NCT00570349
First received: December 6, 2007
Last updated: November 30, 2010
Last verified: November 2010
  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

Resource links provided by NLM:


Further study details as provided by INO Therapeutics:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570349

Locations
United States, Colorado
The Children's Hospital
Denver, Colorado, United States, 80218
Sponsors and Collaborators
INO Therapeutics
Investigators
Principal Investigator: Scott Sagel, MD The Children's Hospital
  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
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Nitric Oxide
Anti-Asthmatic Agents
Antioxidants
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Endothelium-Dependent Relaxing Factors
Free Radical Scavengers
Gasotransmitters
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Respiratory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on November 25, 2014