L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Levels

Asthma Clinical Trial

Official title:

Phase II Study of L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Level

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01841281
• Other study ID #: 271515
• Secondary ID: R01HL105573UCD10
• Status: Completed
• Phase: Phase 2
• Start date: August 2013
• Est. completion date: December 2019

Study information

• Verified date: April 2020
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 2019
• Est. primary completion date: August 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Asthma
• Inflammation

Intervention

Drug:
• L-Arginine
L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
• Placebo
Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.

Locations

Country	Name	City	State
United States	UC Davis CTSC Clinical Research Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
Nicholas Kenyon	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Acute Exacerbation at 3 Months	The primary endpoint of the study is the number of acute moderate exacerbations at 3 months. A moderate asthma exacerbation is defined as any of the following: 1) A drop in morning peak flow rate (PEFR) >30% from baseline on 2 consecutive days (1 event), 2) Need for initiation of oral steroids or am increased dose of inhaled corticosteroids on any two consecutive days (1 event), 3) Doubling of short-acting ß-agonist use (e.g. number of puffs of albuterol) per day for 2 consecutive days (1 event).	3 month
Secondary	Forced Expiratory Volume in One Second (FEV1)/Forced Vital Capacity (FVC)	The secondary endpoint is the change in FEV1/FVC ratio at 3 months. This calcuation is a ratio between the volume of breath exhaled in the first second divided by the total amount of breath exhaled in a vital capacity maneuver. A normal ratio is usually > 70%.	3 month