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L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Levels

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01841281
First Posted: April 26, 2013
Last Update Posted: October 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Nicholas Kenyon, University of California, Davis
  Purpose
The major impact of this study will be to identify the adult severe asthma cohort that will benefit from supplemental L-arginine therapy. The investigators hypothesize that a subset of adult severe asthma patients will respond to supplemental L-arginine and derive clinical benefit from the addition of this therapy to standard-of-care asthma medications. The investigators hypothesize that the patients that benefit most will have low exhaled nitric oxide concentrations (< 20 ppb) at baseline.

Condition Intervention Phase
Asthma Inflammation Drug: L-Arginine Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Study of L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Level

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Asthma Exacerbations [ Time Frame: 3 months ]
    The primary endpoint of the study is the number of acute moderate exacerbations at 3 months. A moderate asthma exacerbation is defined as any of the following: 1) A drop in morning peak flow rate (PEFR) >30% from baseline on 2 consecutive days (1 event), 2) Need for initiation of oral steroids or am increased dose of inhaled corticosteroids on any two consecutive days (1 event), 3) Doubling of short-acting β-agonist use (e.g. number of puffs of albuterol) per day for 2 consecutive days (1 event).


Secondary Outcome Measures:
  • Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) [ Time Frame: 3 months ]
    The secondary endpoint is the change in FEV1/FVC ratio at 3 months.


Enrollment: 54
Study Start Date: August 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low Exhaled Nitric Oxide (NO)

Subjects with a baseline exhaled NO level less than or equal to 20 ppb will be enrolled in the Low Exhaled Nitric Oxide arm.

All subjects will receive L-arginine and placebo in this cross-over design study.

Drug: L-Arginine
L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Other Name: Arginine 1000 (Jarrow Formulas, Los Angeles, CA)
Drug: Placebo
Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.
Active Comparator: High Exhaled Nitric Oxide (NO)

Subjects with a baseline exhaled NO level greater than or equal to 25 ppb will be enrolled in the High Exhaled Nitric Oxide arm.

All subjects will receive L-arginine and placebo in this cross-over design study.

Drug: L-Arginine
L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.
Other Name: Arginine 1000 (Jarrow Formulas, Los Angeles, CA)
Drug: Placebo
Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.

Detailed Description:

We hypothesize that a subset of adult severe asthma patients will respond to supplemental L-arginine and derive clinical benefit from the addition of this therapy to standard-of-care medications. We hypothesize that these patients will have lower exhaled NO concentrations (<20 ppb) and lower nitric oxide synthase 2 (NOS2)/ arginase I (Arg1) mRNA ratios in their airway epithelial cells than "non-responders." The aim is to test the hypothesis that adult severe asthma subjects with exhaled breath NO concentrations < 20 ppb will have fewer American Thoracic Society (ATS)-defined asthma exacerbations over 3 months when treated with L-arginine compared to subjects with exhaled nitric oxide concentration (FeNO) > 25 ppb. The major impact of this study will be to identify the adult severe asthma cohort that will benefit from supplemental L-arginine therapy to define the underlying mechanisms of arginine benefit in asthma. This follows our initial 20 subject trial of L-arginine in asthma subjects (Kenyon et al., Pharmaceuticals 2011) that was designed to determine how L-arginine was metabolized (by testing serum markers) and whether certain participants had clinical benefit.

To do this, we will recruit a total of 50 ATS-defined severe asthmatic subjects with ongoing asthma exacerbations in past two months and enroll them in a randomized, blinded, placebo-controlled, cross-over designed trial of L-arginine and placebo. We will compare 25 subjects with "low" FeNO < 20 with 25 subjects that have "high" FeNO > 25 ppb.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults >18 yrs of age
  • Diagnosis of severe asthma based on American Thoracic Society Workshop definition (Am J Respir Crit Care Med 2000; 162:2341)
  • Active asthma medications of high dose inhaled corticosteroids plus long-acting beta agonist
  • History of recent asthma exacerbations or Asthma control test score < 20/25

Exclusion Criteria:

  • <19 yrs of age
  • Forced expiratory volume 1sec <30% predicted
  • Pregnant or nursing women
  • Current smokers or smoking history > 15 pack years
  • Actively taking or known intolerance to L-arginine
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01841281


Locations
United States, California
UC Davis CTSC Clinical Research Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
Nicholas Kenyon
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Nicholas Kenyon, MD,MS Univ. of California, Davis
  More Information

Responsible Party: Nicholas Kenyon, Professor, University of California, Davis
ClinicalTrials.gov Identifier: NCT01841281     History of Changes
Other Study ID Numbers: 271515
R01HL105573 ( U.S. NIH Grant/Contract )
UCD105573 ( Other Identifier: UC Davis )
First Submitted: April 23, 2013
First Posted: April 26, 2013
Last Update Posted: October 9, 2017
Last Verified: October 2017

Keywords provided by Nicholas Kenyon, University of California, Davis:
Asthma
Severe Asthma

Additional relevant MeSH terms:
Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents