Cystic FibrosisPhase 1/2NCT00570349
Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis
A Phase 1/2 study testing Nitric Oxide for Inhalation and Nitrogen in people with Cystic Fibrosis, run by Mallinckrodt at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Nitric Oxide for Inhalation and Nitrogen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2004to Dec 2008
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Cystic Fibrosis
- Being tested
- Nitric Oxide for Inhalation, Nitrogen
- Keywords
- Inhaled Nitric oxide, Cystic Fibrosis
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric Oxide for InhalationDrug
Also called INO
Nitric oxide will be administered at 20 ppm via nasal cannula over a 44 hour period.
Nitric Oxide for InhalationDrug
Also called INO
Nitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period.
NitrogenDrug
Also called Nitrogen (N2) Grade 5
100% nitrogen (placebo) will be administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose Cohort | Experimental | Subjects in the low dose cohort receive 20 part per million (ppm) of nitric oxide via nasal cannula over a 44 hour period. Receives: Drug: Nitric Oxide for Inhalation |
| High-Dose Cohort | Experimental | Subjects in the high dose cohort receive 40 ppm of nitric oxide via nasal cannula over a 44 hour period. Receives: Drug: Nitric Oxide for Inhalation |
| Nitrogen | Placebo comparator | 100% Nitrogen (placebo) will be administer at 20 ppm or 40 ppm via nasal cannula over a 44 hour period. Receives: Drug: Nitrogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: Baseline and 48 hours
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%
Measured: Baseline and 48 hours
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.
Measured: Baseline and 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2007 (estimated)
- Study startJul 2004
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Scott Sagel, MD, Principal investigator, The Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00570349
- Sponsor's protocol ID
- INOT 50
- Status last verified
- May 2016
- First submitted
- 6 Dec 2007
- Last updated
- 13 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of Inhaled Nitric Oxide in Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00570349
- Acronym / sponsor ID
- INOT 50
- Conditions
- Cystic Fibrosis
- Keywords
- Inhaled Nitric oxide, Cystic Fibrosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Study start
- Jul 2004
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 10 Dec 2007 (estimated)
- Results
- Posted 1 Dec 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose Cohort | Experimental | Drug: Nitric Oxide for InhalationSubjects in the low dose cohort receive 20 part per million (ppm) of nitric oxide via nasal cannula over a 44 hour period. |
| High-Dose Cohort | Experimental | Drug: Nitric Oxide for InhalationSubjects in the high dose cohort receive 40 ppm of nitric oxide via nasal cannula over a 44 hour period. |
| Nitrogen | Placebo comparator | Drug: Nitrogen100% Nitrogen (placebo) will be administer at 20 ppm or 40 ppm via nasal cannula over a 44 hour period. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitric Oxide for InhalationAlso: INONitric oxide will be administered at 20 ppm via nasal cannula over a 44 hour period. | Drug | Low Dose Cohort |
| Nitric Oxide for InhalationAlso: INONitric oxide will be administered at 40 ppm via nasal cannula over a 44 hours period. | Drug | High-Dose Cohort |
| NitrogenAlso: Nitrogen (N2) Grade 5100% nitrogen (placebo) will be administered at 20 ppm or 40 ppm via nasal cannula over a 44 hour period. | Drug | Nitrogen |
Primary outcome
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%.
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%
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Sagel, MD principal investigator
The Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nitric Oxide for Inhalation and Nitrogen in people with Cystic Fibrosis, run by Mallinckrodt at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of Drug, Assessed by Change in Methemoglobin Levels (time frame: Baseline and 48 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2019.