Effects of L-arginine Supplementation in Adults With Moderate to Severe Asthma

Phase 2 Study: GCRC: Effects of L-arginine Supplementation on Exhaled Nitric Oxide and Clinical Exacerbations in Adults With Moderate to Severe Asthma

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: L-arginine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis General Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Moderate to severe persistent asthma
• Subject is stable on same asthma medications for at least one month
• If the subject is a woman of child-bearing age, a negative pregnancy test

Exclusion Criteria:

• Less than 18 yrs/ age
• Baseline Forced Expiratory Volume in 1 second (FEV1) <40% predicted
• Known or suspected allergy to L-arginine
• Pregnant women, nursing women, or women actively trying to achieve pregnancy
• Current smokers
• Subjects with more than a 15 pack-year history of smoking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arginine; Enrolled subjects will take L-arginine orally, at 0.1 g/kg/day. Subjects will take three to four 1 g capsules (based on weight) of L-arginine twice daily for three months. L-arginine capsules were obtained from Jarrow Pharmaceuticals.	Drug: L-arginine; subjects will take matching 0.01 g/kg/day of L-arginine in divided doses for thre months.; Other Names: Arginine 1000
Placebo Comparator: Placebo; Enrolled subjects took three to four placebo capsules that matched color and size of the intervention twice daily for three months. Matching placebo capsules were obtained from Jarrow Pharmaceuticals.	Drug: Placebo; Placebo tablets that match the L-arginine intervention tablets will be given for three months; Other Names: Matching placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Asthma Exacerbations in Three Months	Asthma exacerbation is a composite endpoint. An asthma exacerbation is defined as any of the following: a) a drop in the morning peak expiratory flow rate (PEF) >30% from baseline on 2 consecutive days, b) a need for initiation of or increased dose of inhaled corticosteroids, or the c) doubling of short-acting rescue β-agonist drug use (e.g.Albuterol) on two consecutive days. Any one of these three counts as one asthma exacerbation.	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
L-arginine Serum Concentration	90 days

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: National Institutes of Health (NIH); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Nicholas Kenyon, MD, University of California, Davis

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: January 19, 2006
• First Submitted That Met QC Criteria: January 19, 2006
• First Posted (Estimate): January 23, 2006

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: May 25, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Airway Inflammation; Moderate persistent asthma; Severe Persistent Asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 200412788; UL1RR024146 (U.S. NIH Grant/Contract); K30-04-Z001 (Other Identifier: UC Davis)