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

October 31, 2019 updated by: Mallinckrodt
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • The Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • INO
Drug: Nitric Oxide for Inhalation
Nitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period.
Other Names:
  • 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 20 ppm via nasal cannula over a 44 hour period.
Other Names:
  • INO
Drug: Nitric Oxide for Inhalation
Nitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period.
Other Names:
  • 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 Names:
  • Nitrogen (N2) Grade 5

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels
Time Frame: 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%.
Baseline and 48 hours
Change in Oxygen Saturation
Time Frame: 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%
Baseline and 48 hours
Change in Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 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.
Baseline and 48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mallinckrodt

Investigators

  • Principal Investigator: Scott Sagel, MD, The Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

December 1, 2008

Study Registration Dates

First Submitted

December 6, 2007

First Submitted That Met QC Criteria

December 6, 2007

First Posted (Estimate)

December 10, 2007

Study Record Updates

Last Update Posted (Actual)

November 13, 2019

Last Update Submitted That Met QC Criteria

October 31, 2019

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INOT 50

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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