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

Phase 2

Completed

Conditions: Asthma

Interventions: Drug: Placebo
Drug: L-arginine

Registration Number: NCT00280683

Lead Sponsor: University of California, Davis

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Arginine	L-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.

Primary Outcome Measures

Name	Time	Method
Number of Asthma Exacerbations in Three Months	3 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.

Secondary Outcome Measures