Nontuberculous Mycobacterium InfectionPhase 2NCT03748992
A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection
A Phase 2 study testing gNO in people with Nontuberculous Mycobacterium Infection, run by Medical University of South Carolina at 2 sites in United States.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of open-label exposure of gNO in patients with NTM lung disease. Subjects will receive the study drug by inhaling through a nasal mask. Subjects will be treated for 3 weeks (5 days per week) and followed monthly for 3 months. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Nontuberculous Mycobacterium Infection
- What is being tested?
- gNO
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Jan 2019to 26 Mar 2020
- Phase
- Phase 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects are >18 years of age and able to provide informed consent.
- Subjects have NTM lung disease as defined by each of the following:
- Sputum cultures positive for NTM (MAC or M abscessus) Radiologic studies that demonstrate features consistent with disease such as nodular bronchiectasis and/or cavities Symptoms consistent with disease including respiratory (e.g. cough, sputum production, hemoptysis, chest pain) and constitutional (e.g. fevers, night sweats, fatigue, myalgias, arthralgias, weight loss) Subjects are able to produce sputum for culture (either spontaneous or induced).
- Subjects have a history of persistently positive sputum cultures for NTM defined as >4 number of cultures over 24 months with >75% positive AND a positive culture in the last 3 months.
- Clinically stable with no significant changes in health status within 14 days prior to Screening or Day 1 Subjects are willing and able to perform requirements of the study.
Who cannot join
- Smoking history in the prior 6 months Significant hemoptysis within 30 days prior to screening (>5 ml of blood in one coughing episode or >30 ml of blood in a 24 hour period) Forced expiratory volume at one second (FEV1) <40% of predicted On supplemental oxygen or SaO2 <90% at screening or Day 1, or within 30 days prior to enrollment.
- Known cardiac (left heart) insufficiency (defined as LVEF <35%) prior to screening Known pulmonary hypertension Known or suspected hemoglobinopathy Initiation of NTM treatment regimen or a change in the regimen was made in the prior 6 months. Subjects on active treatment can be enrolled if they have been on a stable anti-NTM regimen for at least 6 months.
- Initiation of new chronic therapy within 4 weeks prior to screening Use of drugs known to increase methemoglobin (see 12.2.7) at screening
- Any of the following abnormal lab values at screening:
- 6-GPD deficiency Hemoglobin <10g/dl Platelet count <100,000/mm3 Prothrombin time international ratio (INR) >1.5 Abnormal liver function defined as any two of the following ALT >3x ULN AST >3x ULN ALP >3x ULN GGT >3x ULN
- Abnormal renal function defined as:
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- Calculated Creatinine Clearance <50 ml (as calculated by Cockcroft/Gault)
- For women of child bearing potential:
- Positive pregnancy test at screening or Lactating or Unwilling to practice a medically acceptable form of contraception from screening to Day 15 (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent) Use of an investigational drug within 30 days prior to screening Intravenous or oral steroids (>10 mg/d prednisone equivalent) in the 14 days prior to screening Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the subject.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Medical University of South Carolina
Charleston, South Carolina, 29425
Oregon Health and Science University
Portland, Oregon, 97239
About this study
The purpose of this study is to evaluate the efficacy and safety of open-label exposure of gNO in patients with NTM lung disease. Subjects will receive the study drug by inhaling through a nasal mask. Subjects will be treated for 3 weeks (5 days per week) and followed monthly for 3 months.
- Conditions
- Nontuberculous Mycobacterium Infection
- Being tested
- gNO
- Medical subject headings
- Mycobacterium Infections, Nontuberculous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gNODrug
This is a proof-of-concept study in which all subjects will be treated with gNO (i.e. no control) to see if there can be a microbiological effect by conversion to negative sputum cultures and how long that effect can be sustained following treatment.
Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months.
The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires.
| Study group | Role | What they receive |
|---|---|---|
| gNO | Experimental | Subjects will be receiving nitric oxide every week day for 3 weeks. Receives: Drug: gNO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Patients With Negative Sputum Culture
Sputum culture will be assessed for any sputum growth. A negative culture represents no mycobacterial growth.
Measured: End of Treatment (Day 15)
Secondary outcomes (2)
Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)
Adverse Events will be assessed by patient reporting and routine lab work
Measured: Treatment Day 1 through End of Treatment (3 Months)
Number of Participants With a Reduction in Semiquantitative Cultures
Semiquantitative Culture Score is an assessment of bacterial burden with a lower score suggesting a lesser bacterial burden. The Semiquantitative Culture Score at Day 15 was compared to baseline, and a reduction in the Semiquantitative Culture Score suggests a reduced bacterial burden with treatment.
Cultures were reported as positive if growth occurs in broth medium only; growth on broth medium plus solid medium cultures with countable colonies will be reported as 0-49 colonies, 1+; solid medium growth with 50-99 colonies, 2+; solid medium growth with 100-199 colonies; 3+, solid medium growth with 200-299 colonies; and 4+, solid medium growth with at least 300 colonies. For data analysis, each culture was scored as follows: 0, no growth in broth or solid medium; 1, broth medium growth only; 2, countable colonies (<50 colonies) on solid medium; and 3-6, 1+ to 4+ growth on solid medium, respectively.
Measured: At day 15 from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2018
- Study start28 Jan 2019
- Primary completion26 Mar 2020
- Study completion26 Mar 2020
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 Nontuberculous Mycobacterium InfectionStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- Cystic Fibrosis Foundation, Oregon Health and Science University
- Responsible party
- Sponsor
- Investigators
- Patrick Flume, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03748992
- Sponsor's protocol ID
- Pro 00081838
- Status last verified
- May 2021
- First submitted
- 19 Nov 2018
- Last updated
- 18 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection
- ClinicalTrials.gov ID
- NCT03748992
- Acronym / sponsor ID
- Pro 00081838
- Conditions
- Nontuberculous Mycobacterium Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- Cystic Fibrosis Foundation, Oregon Health and Science University
- Study start
- 28 Jan 2019 (actual)
- Primary completion
- 26 Mar 2020 (actual)
- Study completion
- 26 Mar 2020 (actual)
- First posted
- 21 Nov 2018 (actual)
- Results
- Posted 18 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety of open-label exposure of gNO in patients with NTM lung disease. Subjects will receive the study drug by inhaling through a nasal mask. Subjects will be treated for 3 weeks (5 days per week) and followed monthly for 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| gNO | Experimental | Drug: gNOSubjects will be receiving nitric oxide every week day for 3 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects are >18 years of age and able to provide informed consent.
- Sputum cultures positive for NTM (MAC or M abscessus) Radiologic studies that demonstrate features consistent with disease such as nodular bronchiectasis and/or cavities Symptoms consistent with disease including respiratory (e.g. cough, sputum production, hemoptysis, chest pain) and constitutional (e.g. fevers, night sweats, fatigue, myalgias, arthralgias, weight loss) Subjects are able to produce sputum for culture (either spontaneous or induced).
- Subjects have a history of persistently positive sputum cultures for NTM defined as >4 number of cultures over 24 months with >75% positive AND a positive culture in the last 3 months.
- Clinically stable with no significant changes in health status within 14 days prior to Screening or Day 1 Subjects are willing and able to perform requirements of the study.
Key exclusion criteria (9 listed)
- Smoking history in the prior 6 months Significant hemoptysis within 30 days prior to screening (>5 ml of blood in one coughing episode or >30 ml of blood in a 24 hour period) Forced expiratory volume at one second (FEV1) <40% of predicted On supplemental oxygen or SaO2 <90% at screening or Day 1, or within 30 days prior to enrollment.
- Known cardiac (left heart) insufficiency (defined as LVEF <35%) prior to screening Known pulmonary hypertension Known or suspected hemoglobinopathy Initiation of NTM treatment regimen or a change in the regimen was made in the prior 6 months. Subjects on active treatment can be enrolled if they have been on a stable anti-NTM regimen for at least 6 months.
- Initiation of new chronic therapy within 4 weeks prior to screening Use of drugs known to increase methemoglobin (see 12.2.7) at screening
- 6-GPD deficiency Hemoglobin <10g/dl Platelet count <100,000/mm3 Prothrombin time international ratio (INR) >1.5 Abnormal liver function defined as any two of the following ALT >3x ULN AST >3x ULN ALP >3x ULN GGT >3x ULN
- Calculated Creatinine Clearance <50 ml (as calculated by Cockcroft/Gault)
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 |
|---|---|---|
| gNOThis is a proof-of-concept study in which all subjects will be treated with gNO (i.e. no control) to see if there can be a microbiological effect by conversion to negative sputum cultures and how long that effect can be sustained following treatment. Participants will be treated for 3 weeks (5 days per week), Monday through Friday, and followed monthly for 3 months. The treatment period includes a physical exam, vital signs, blood tests, echocardiogram, spirometry test, sputum sample, questionnaires, and the inhalation gas treatment. During the inhalation gas treatment, participants will wear a face mask (similar to an oxygen mask) and will be given nitric oxide gas through the participants nose for three treatments with fifty minutes each time. They will then be followed up monthly during the Follow-up period with tests that include a physical exam and questionnaires. | Drug | gNO |
Primary outcome
Percent Patients With Negative Sputum Culture
Time frame: End of Treatment (Day 15)
Sputum culture will be assessed for any sputum growth. A negative culture represents no mycobacterial growth.
2 secondary outcomes
Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE (Common Terminology Criteria for Adverse Events)
Time frame: Treatment Day 1 through End of Treatment (3 Months)
Number of Participants With a Reduction in Semiquantitative Cultures
Time frame: At day 15 from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Patrick Flume principal investigator
Medical University of South Carolina
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing gNO in people with Nontuberculous Mycobacterium Infection, run by Medical University of South Carolina at 2 sites 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 5 inclusion and 9 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 18 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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 18 May 2021). 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?
Percent Patients With Negative Sputum Culture (time frame: End of Treatment (Day 15)). 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 18 May 2021.