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

NCT ID: NCT00280683

Last Updated: 2017-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2008-12-31

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

L-arginine

Intervention Type: DRUG

subjects will take matching 0.01 g/kg/day of L-arginine in divided doses for thre months.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets that match the L-arginine intervention tablets will be given for three months

Interventions

L-arginine

subjects will take matching 0.01 g/kg/day of L-arginine in divided doses for thre months.

Intervention Type: DRUG

Placebo

Placebo tablets that match the L-arginine intervention tablets will be given for three months

Intervention Type: DRUG

Other Intervention Names

Arginine 1000; Matching placebo tablets

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicholas Kenyon, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California, Davis General Clinical Research Center

Sacramento, California, United States

Countries

United States

Other Identifiers

UL1RR024146

Identifier Type: NIH

Identifier Source: secondary_id

View Link

K30-04-Z001

Identifier Type: OTHER

Identifier Source: secondary_id

200412788

Identifier Type: -

Identifier Source: org_study_id