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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00280683
• Other study ID #: 200412788
• Secondary ID: UL1RR024146K30-0
• Status: Completed
• Phase: Phase 2
• First received: January 19, 2006
• Last updated: May 25, 2017
• Start date: December 2004
• Est. completion date: December 2008

Study information

• Verified date: May 2017
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• L-arginine
subjects will take matching 0.01 g/kg/day of L-arginine in divided doses for thre months.
• Placebo
Placebo tablets that match the L-arginine intervention tablets will be given for three months

Locations

Country	Name	City	State
United States	University of California, Davis General Clinical Research Center	Sacramento	California

Sponsors (3)

Lead Sponsor	Collaborator
University of California, Davis	National Center for Research Resources (NCRR), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 ß-agonist drug use (e.g.Albuterol) on two consecutive days. Any one of these three counts as one asthma exacerbation.	3 months
Secondary	L-arginine Serum Concentration		90 days