Clinical trial NCT00280683: Effects of L-arginine Supplementation in Adults With Moderate to Severe Asthma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Airway Inflammation
Moderate persistent asthma
Severe Persistent Asthma
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Center for Research Resources (NCRR)
First posted: 2006-01-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Asthma Exacerbations in Three Months
timeFrame: 3 months
Secondary outcomes:
measure: L-arginine Serum Concentration
timeFrame: 90 days
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis General Clinical Research Center
state: California
Study officials:
affiliation: University of California, Davis
name: Nicholas Kenyon, MD
role: PRINCIPAL_INVESTIGATOR
References: