Inhaled Nitric Oxide for Patients With MABSC

Study Overview
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Brief Summary
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A Prospective, Open labeled, multi-Center, Evaluation of the Efficacy Safety and Tolerability of Nitric Oxide Given Intermittently via Inhalation to Subjects with NTM (specifically MABSC) Nitric Oxide (NO) has been shown to play a critical role in various biological functions. In the airways, NO is considered to play a key role in the innate immune system in which the first-line of host defense against microbes is built. In vitro studies suggested that NO, in part per million (ppm) concentrations, possesses anti-microbial activity against a wide variety of phyla including fungi, and antibiotic-resistance bacteria. In this study the investigators wish to evaluate the efficacy, safety and tolerability of 160 ppm Nitric Oxide intermittently delivered via inhalation to subjects infected with Non-tuberculosis mycobacteria (NTM), specifically with MABSC.

Official Title
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A Prospective, Open Labeled, Multi-Center, Evaluation of the Efficacy Safety and Tolerability of Nitric Oxide Given Intermittently Via Inhalation to Subjects With NTM (Specifically MABSC)

Conditions
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Mycobacterium Abscessus Infection

Intervention / Treatment
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* Drug: Nitric Oxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects (Male or female) between 6 to 65 years old Diagnosis of pulmonary non-tuberculosis mycobacterial lung disease in accordance with the 2007 ATS/IDSA criteria with evidence of nodular bronchiectasis and/or cavitary disease by chest computed tomography (CT) and by culture. History of at least 6 months chronic infection with Mycobacterium abscessus. Mycobacterium abscessus positive sputum sample at screening or prior to screening. Receiving ATS/IDSA guidelines-based treatment regimen defined as: adherent to a multi-drug regimen for at least 6 months prior to screening with persistently positive mycobacterial abscessus cultures. FEV1 ≥ 30% at screening as well as baseline. Ability to produce sputum or be willing to undergo an induction of sputum for clinical evaluation. Life expectancy ≥1 year Ability to perform 6MWT, but not to exceed a distance of 700 meters during screening. Ability to understand and comply with study requirements. Approved and signed informed consent by subject and/or by parent/legal guardian (depending on subject's age). Exclusion Criteria: Breastfeeding or pregnancy as evidenced by a positive pregnancy test. Subjects diagnosed with methemoglobinemia, immunodeficiency, heart disease, pulmonary hypertension and/or high blood pressure. Use of an investigational drug during the last 30 days prior enrollment and/or the subject is expected to participate in a new study within five months from enrollment to this study. History of frequent epistaxis (>1 episode/month). Significant hemoptysis during the last 30 days prior to enrolment (>30 Ml of blood in a 24-hour period). Methemoglobin level >2% at screening. Patients on inconsistant dosage of systemic steroids (any formulation) 30 days prior to enrolment. History of illicit drug or medication abuse within 1 year of screening. History of lung transplantation. History of daily, continuous oxygen supplementation. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data. Pulmonary tuberculosis requiring treatment or treated within 2 years prior to screening. Any change in chronic NTM multi-drug regimen within 28 days prior to study day 1.

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitric Oxide treatment<br> | Drug: Nitric Oxide<br>* Subjects will be treated with 91 thirty minute sessions of 160 ppm Nitric Oxide with at least 3 hours between each session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety measured by NO-related Serious Adverse Events |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six minute walk test |  | 21 days | 
| Mycobacterium Abscesuss load in sputum |  | 81 days | 
| NO-related AE's such as elevation of methemoglobin and elevation of NO2 during treatment |  | 21 days | 
| Type and frequency of occurrence of NO-related Adverse Events (AE's) and Serious AE's (SAE's) |  | 51 days |