The Effects of NOx and Conjugated Linoleic Acid on Asthmatics
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Obesity is an asthma comorbidity associated with increased severity, poor control, reduced
      steroid responsiveness and greater exacerbation and healthcare utilization rates. These
      associations are not explained by having a greater degree of Th-2 inflammation. Rather, the
      obese asthma phenotype defined in several cluster studies, has paradoxically reduced levels
      of Th-2 biomarkers, including sputum eosinophils and exhaled nitric oxide (NO). The
      investigators previous research has shown that the inverse relation between increased body
      mass index (BMI) and reduced exhaled NO, may be explained by a metabolic imbalance
      characterized by lower L-arginine and greater asymmetric di-methyl arginine (ADMA) levels.
      Having a low L-arginine/ADMA ratio has been shown to inhibit and uncouple all isoforms of
      nitric oxidase synthase (NOS), thereby reducing NO bioavailability and promoting oxidative
      stress through enhanced superoxide production. In obese asthmatics, this imbalance not only
      correlates with exhaled NO, but also with lower FEV1% and poorer asthma-related quality of
      life. Yet the effect of obesity in asthma is unlikely to be solely dependent on a single
      mechanism. Other factors, such as increased Th1 and Th-17-mediated inflammation have been
      shown to occur in human and animal models. Given all of these potential avenues, it is
      imperative that an intervention is sufficiently pleiotropic that can, in addition to
      restoring airway NO levels, also reduce other obesity-related non-Th2 mechanism of
      inflammation. The investigators hypothesize that treatment with conjugated linolenic acid
      (CLA) + nitrate and nitrite (together known as NOx), will restore NO airway bioavailability,
      reduce oxidative stress and improve airway inflammation in obese asthmatics. To test this
      hypothesis, the investigators propose a phase II pilot study in which obese asthmatics with
      metabolic syndrome, will be treated orally with CLA+NOx for 8 weeks, in an open label study
      design to assess pre to post-intervention changes in airway and systemic biomarkers, and to
      determine the effects on lung function and bronchial hyperresponsiveness. Participants will
      undergo a pre and post intervention bronchoscopy. The results obtained from this project will
      be greatly informative to our understanding of the obese - asthma pathophysiology and for the
      development of clinical trials to determine the potential benefit of this intervention in
      improving health outcomes.
    

Intervention name(s): Conjugated Linolenic Acid; Sodium Nitrite; Sodium Nitrate
Intervention type(s): Dietary Supplement; Drug; Drug
Intervention description(s): 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)
Other intervention name(s): conjugated linolenic acid (CLA)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Asthma; Obesity; conjugated linolenic acid; nitrate; nitrite; nutritional supplements