The Effects of NOx and Conjugated Linoleic Acid on Asthmatics
Condition: Asthma
MeSH terms: Asthma
Intervention: Conjugated Linolenic Acid; Sodium Nitrite; Sodium Nitrate
Intervention description: CLA is a polyunsaturated fatty acid Subjects will receive capsules for daily oral administration at the dose of 3 g/day; Subjects will receive capsules for daily oral administration at the dose of 20 mg (2 x 10 mg); Subjects will receive capsules for daily oral administration at the dose of 1g (2 x 500 mg)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Asthma; Obesity; conjugated linolenic acid; nitrate; nitrite; nutritional supplements

Summary:

      This study will examine the hypothesis that in obese asthmatics; treatment with NOx + CLA is
      well tolerated, safe and will increase eNO while reducing airway oxidative stress. Allied
      with this, the investigators will define whether supplementing with this bioactive mediator
      modifies the airway microbiome, and reduces airway inflammation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adequate completion of informed consent process with written documentation

          -  Male and female patients, ≥ 18 - 65 yrs old

          -  Diagnosis of asthma: based on previous physician diagnosis and either baseline
             pre-bronchodilator FEV1 50% or greater predicted with a 12% or greater bronchodilator
             response to 4 puffs of albuterol or PC20 methacholine (16 mg) if no BD response.If the
             subject is not currently on an ICS/ ICS LABA, PC20 should be < 8 mg, if no BD
             response. Spirometry results within the prior 24 months located in the subject's
             medical records can be used to determine eligibility, if available.

          -  All racial/ethnic backgrounds with a diagnosis of asthma for ≥6 months

          -  Smoking history ≤10 pack years and no smoking in the last year

          -  BMI ≥ 30

          -  If subject is on ICS or ICS/LABA therapy- 30 days on a stable dose (up to 1,000 mcg
             daily fluticasone equivalent)

          -  Asthma diagnosed at age 9 or later

        Exclusion Criteria:

          -  Respiratory tract infection within the last 4 weeks

          -  Oral or systemic CS burst within the last 4 weeks

          -  Asthma-related hospitalization within the last 2 months

          -  Asthma-related ER visit within the previous 4 weeks

          -  Significant or uncontrolled concomitant medical illness including (but not limited to)
             heart disease, cancer, diabetes

          -  Chronic renal failure (creatinine > 2.0) at screening (Associated with higher ADMA
             levels)

          -  Current statins use (statins lower ADMA levels), patients may stop and re-enroll after
             2 weeks of stopping statins

          -  Positive pregnancy test

          -  Intolerance or allergy to the intervention drugs

          -  Current or recent (within 30 days) in an investigational treatment study.

          -  Unable or unlikely to complete study assessments or the study intervention (i.e.
             bronchoscopy) poses undue risk to patient in the opinion of the Investigator.

          -  Any kind of oral nitrates such as nitroglycerin or already taking supplements

          -  History of ICU admission/intubation due to asthma in the past year;

          -  More than three systemic corticosteroid requiring asthma exacerbations in the past
             year

          -  Systemic steroid dependent asthma (no daily oral steroids- short term therapy for
             asthma exacerbation is permitted)

          -  Use of mouthwash containing chlorhexidine (lowers NO) within 1 week prior to screening
             and throughout the study

          -  Untreated sleep apnea

          -  Hgb A1C ≥7

          -  Daily use of PPI's (Proton Pump Inhibitor) or H2 Blockers for GERD (it is permitted to
             take on an occasional basis- no more than 1x per week. If participants wash out of
             these meds for 1 week, they can enroll)

          -  Use of biologics for asthma/allergies unless there is a 4 month washout prior to
             enrollment (the washout for biologics is done for clinical reasons and not
             specifically for inclusion for the study).

          -  Drug and/or alcohol abuse for ≥1 year

          -  Breastfeeding

          -  Any other condition and/or situation that causes the investigator to deem a subject
             unsuitable for the study (e.g. due to expected study medication non-compliance,
             inability to medically tolerate the study procedures, or a subject's unwillingness to
             comply with study-related procedures.