Clinical trial NCT01841281: L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Levels
Official title: Phase II Study of L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Level
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Inflammation
Keywords: Asthma
Severe Asthma
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-04-26
Enrollment: 54
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The major impact of this study will be to identify the adult severe asthma cohort that will benefit from supplemental L-arginine therapy. The investigators hypothesize that a subset of adult severe asthma patients will respond to supplemental L-arginine and derive clinical benefit from the addition of this therapy to standard-of-care asthma medications. The investigators hypothesize that the patients that benefit most will have low exhaled nitric oxide concentrations (\< 20 ppb) at baseline.

Detailed description: We hypothesize that a subset of adult severe asthma patients will respond to supplemental L-arginine and derive clinical benefit from the addition of this therapy to standard-of-care medications. We hypothesize that these patients will have lower exhaled NO concentrations (\<20 ppb) and lower nitric oxide synthase 2 (NOS2)/ arginase I (Arg1) mRNA ratios in their airway epithelial cells than "non-responders." The aim is to test the hypothesis that adult severe asthma subjects with exhaled breath NO concentrations \< 20 ppb will have fewer American Thoracic Society (ATS)-defined asthma exacerbations over 3 months when treated with L-arginine compared to subjects with exhaled nitric oxide concentration (FeNO) \> 25 ppb. The major impact of this study will be to identify the adult severe asthma cohort that will benefit from supplemental L-arginine therapy to define the underlying mechanisms of arginine benefit in asthma. This follows our initial 20 subject trial of L-arginine in asthma subjects (Kenyon et al., Pharmaceuticals 2011) that was designed to determine how L-arginine was metabolized (by testing serum markers) and whether certain participants had clinical benefit.

To do this, we will recruit a total of 50 ATS-defined severe asthmatic subjects with ongoing asthma exacerbations in past two months and enroll them in a randomized, blinded, placebo-controlled, cross-over designed trial of L-arginine and placebo. We will compare 25 subjects with "low" FeNO \< 20 with 25 subjects that have "high" FeNO \> 25 ppb.

Eligibility criteria: Inclusion Criteria:

* Adults \>18 yrs of age
* Diagnosis of severe asthma based on American Thoracic Society Workshop definition (Am J Respir Crit Care Med 2000; 162:2341)
* Active asthma medications of high dose inhaled corticosteroids plus long-acting beta agonist
* History of recent asthma exacerbations or Asthma control test score \< 20/25

Exclusion Criteria:

* \<19 yrs of age
* Forced expiratory volume 1sec \<30% predicted
* Pregnant or nursing women
* Current smokers or smoking history \> 15 pack years
* Actively taking or known intolerance to L-arginine

Primary outcomes:
measure: Number of Acute Exacerbation at 3 Months
timeFrame: 3 month
Secondary outcomes:
measure: Forced Expiratory Volume in One Second (FEV1)/Forced Vital Capacity (FVC)
timeFrame: 3 month
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis CTSC Clinical Research Center
state: California
Study officials:
affiliation: Univ. of California, Davis
name: Nicholas Kenyon, MD,MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liao SY, Showalter MR, Linderholm AL, Franzi L, Kivler C, Li Y, Sa MR, Kons ZA, Fiehn O, Qi L, Zeki AA, Kenyon NJ. l-Arginine supplementation in severe asthma. JCI Insight. 2020 Jul 9;5(13):e137777. doi: 10.1172/jci.insight.137777.