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A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03748992
Recruitment Status : Completed
First Posted : November 21, 2018
Results First Posted : May 18, 2021
Last Update Posted : May 18, 2021
Cystic Fibrosis Foundation
Oregon Health and Science University
Information provided by (Responsible Party):
Medical University of South Carolina

Brief 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.

Condition or disease Intervention/treatment Phase
Nontuberculous Mycobacterium Infection Drug: gNO Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection
Actual Study Start Date : January 28, 2019
Actual Primary Completion Date : March 26, 2020
Actual Study Completion Date : March 26, 2020

Arm Intervention/treatment
Experimental: gNO
Subjects will be receiving nitric oxide every week day for 3 weeks.
Drug: gNO

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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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) ]
    Adverse Events will be assessed by patient reporting and routine lab work

  2. Number of Participants With a Reduction in Semiquantitative Cultures [ Time Frame: At day 15 from baseline ]

    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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

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.

Exclusion Criteria:

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:

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03748992

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United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Medical University of South Carolina
Cystic Fibrosis Foundation
Oregon Health and Science University
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Principal Investigator: Patrick Flume Medical University of South Carolina
  Study Documents (Full-Text)

Documents provided by Medical University of South Carolina:
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Responsible Party: Medical University of South Carolina Identifier: NCT03748992    
Other Study ID Numbers: Pro 00081838
First Posted: November 21, 2018    Key Record Dates
Results First Posted: May 18, 2021
Last Update Posted: May 18, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Communicable Diseases
Mycobacterium Infections
Mycobacterium Infections, Nontuberculous
Disease Attributes
Pathologic Processes
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses