A Proof of Concept Study of Inhaled Nitric Oxide for Adults With Pulmonary Non-Tuberculous Mycobacterial Infection
Condition: Nontuberculous Mycobacterium Infection
MeSH terms: Infections; Communicable Diseases; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous
Intervention: gNO
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.