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

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ClinicalTrials.gov Identifier: NCT00280683
Recruitment Status : Completed
First Posted : January 23, 2006
Results First Posted : June 5, 2013
Last Update Posted : May 30, 2017
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
University of California, Davis

Tracking Information
First Submitted Date  ICMJE January 19, 2006
First Posted Date  ICMJE January 23, 2006
Results First Submitted Date  ICMJE December 6, 2012
Results First Posted Date  ICMJE June 5, 2013
Last Update Posted Date May 30, 2017
Study Start Date  ICMJE December 2004
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2013)
Number of Asthma Exacerbations in Three Months [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 19, 2006)
Number of asthma exacerbations in 3 months
Change History Complete list of historical versions of study NCT00280683 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2013)
L-arginine Serum Concentration [ Time Frame: 90 days ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2006)
  • Lung function
  • Exhaled nitric oxide levels
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of L-arginine Supplementation in Adults With Moderate to Severe Asthma
Official Title  ICMJE Phase 2 Study: GCRC: Effects of L-arginine Supplementation on Exhaled Nitric Oxide and Clinical Exacerbations in Adults With Moderate to Severe Asthma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • 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
  • Drug: Placebo
    Placebo tablets that match the L-arginine intervention tablets will be given for three months
    Other Name: Matching placebo tablets
Study Arms  ICMJE
  • 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.
    Intervention: Drug: L-arginine
  • 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.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 19, 2009)
20
Original Enrollment  ICMJE
 (submitted: January 19, 2006)
40
Actual Study Completion Date  ICMJE December 2008
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00280683
Other Study ID Numbers  ICMJE 200412788
UL1RR024146 ( U.S. NIH Grant/Contract )
K30-04-Z001 ( Other Identifier: UC Davis )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, Davis
Study Sponsor  ICMJE University of California, Davis
Collaborators  ICMJE
  • National Institutes of Health (NIH)
  • National Center for Research Resources (NCRR)
Investigators  ICMJE
Principal Investigator: Nicholas Kenyon, MD University of California, Davis
PRS Account University of California, Davis
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP