Effects of L-arginine Supplementation in Adults With Moderate to Severe Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      Nitric oxide is an important marker of airway inflammation in asthma. Nitric oxide may have a
      protective role in patients with moderate to severe asthma. The investigators believe that a
      natural amino acid, L-arginine, that augments nitric oxide levels can decrease asthma
      exacerbations and improve the asthma care of moderate to severe asthma patients.

      This study is a randomized, placebo controlled trial in which subjects will receive either 3
      months of L-arginine supplementation or a placebo. The investigators will monitor subjects'
      symptoms, the number of asthma exacerbations, and lung function. In addition, we will draw
      blood, obtain induced sputum samples and measure exhaled breath nitric oxide levels at each
      monthly visit.
    

Detailed description: 
      The primary objective of this 3 month clinical study is to determine if supplemental
      L-arginine can decrease the number of asthma exacerbations in patients with severe asthma.
      L-arginine, a natural amino acid, produces nitric oxide (NO) when it is converted to
      L-citrulline in the presence of the nitric oxide synthase enzymes. We and others have found
      that NO can protect against allergic airway inflammation, airway hyperresponsiveness and
      airway fibrosis in various animal models. In addition, we have found that arginase I
      expression correlates strongly with the lymphocyte and eosinophil influx into the lung and
      this enzyme may regulate the airway inflammatory response. Our central hypothesis is that
      L-arginine will increase NO levels in the lung and decrease the number of acute exacerbations
      of asthma. It may do this by either decreasing the number of Th2 lymphocytes or
      down-regulating arginase I expression or both.

      Our specific aims are, therefore,

        1. To test the hypothesis, in a randomized, double-blinded, placebo controlled trial, that
           3 months of L-arginine supplementation will decrease the number of acute asthma
           exacerbations in severe asthmatic patients,

        2. To determine whether L-arginine decreases the ratio of peripheral blood Th2 to Th1
           lymphocytes and

        3. To determine whether L-arginine will modulate serum arginase I/II levels and their
           downstream products.

      Patients will be recruited primarily from the UC Davis Asthma Network (UCAN) clinics, which
      focus on the care of severe asthmatics, and the study will be performed at the UC Davis/VA
      General Clinical Research Center.
    

Intervention name(s): L-arginine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): subjects will take matching 0.01 g/kg/day of L-arginine in divided doses for thre months.; Placebo tablets that match the L-arginine intervention tablets will be given for three months
Other intervention name(s): Arginine 1000; Matching placebo tablets
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Airway Inflammation; Moderate persistent asthma; Severe Persistent Asthma