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

This study has been completed.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Nicholas Kenyon, University of California, Davis
ClinicalTrials.gov Identifier:
NCT00280683
First received: January 19, 2006
Last updated: April 26, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: L-arginine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Number of Asthma Exacerbations in Three Months [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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:
  • L-arginine Serum Concentration [ Time Frame: 90 days ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: December 2004
Study Completion Date: December 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Matching placebo tablets

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

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00280683

Locations
United States, California
University of California, Davis General Clinical Research Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Investigators
Principal Investigator: Nicholas Kenyon, MD University of California, Davis
  More Information

No publications provided

Responsible Party: Nicholas Kenyon, Associate Professor of Medicine, University of California, Davis
ClinicalTrials.gov Identifier: NCT00280683     History of Changes
Other Study ID Numbers: K30-04-Z001, UL1RR024146
Study First Received: January 19, 2006
Results First Received: December 6, 2012
Last Updated: April 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Davis:
Airway Inflammation
Moderate persistent asthma
Severe Persistent Asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on August 28, 2014