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

NCT01841281 | Completed Phase 2 Results DMC

• 3 other identifiers: 271515R01HL105573UCD105573
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Asthma; Inflammation

Keywords

Asthma; Severe Asthma

Outcome Measures

Primary Outcomes (1)

• Number of Acute Exacerbation at 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).

  3 month

Secondary Outcomes (1)

• Forced Expiratory Volume in One Second (FEV1)/Forced Vital Capacity (FVC)

  3 month

Study Arms (2)

Low Exhaled Nitric Oxide (NO)

ACTIVE COMPARATOR

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; Drug: Placebo

High Exhaled Nitric Oxide (NO)

ACTIVE COMPARATOR

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; Drug: Placebo

Interventions

L-Arginine DRUG

L-arginine tablets containing 1 g of elemental L-arginine (1204 mg of L-arginine HCL) developed by Jarrow Formulas in Los Angeles.

Also known as: Arginine 1000 (Jarrow Formulas, Los Angeles, CA)

High Exhaled Nitric Oxide (NO); Low Exhaled Nitric Oxide (NO)

Placebo DRUG

Matching placebo tablets do not contain L-arginine. Placebo tablets were manufactured by Jarrow Formulas and contain cellulose and other excipients.

High Exhaled Nitric Oxide (NO); Low Exhaled Nitric Oxide (NO)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \<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

Sponsors & Collaborators

• Nicholas Kenyon: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

UC Davis CTSC Clinical Research Center

Sacramento, California, 95817, United States

Location

Related Publications (1)

• Liao SY, Showalter MR, Linderholm AL, Franzi L, Kivler C, Li Y, Sa MR, Kons ZA, Fiehn O, Qi L, Zeki AA, Kenyon NJ. l-Arginine supplementation in severe asthma. JCI Insight. 2020 Jul 9;5(13):e137777. doi: 10.1172/jci.insight.137777.

  PMID: 32497023 DERIVED

MeSH Terms

Conditions

Asthma; Inflammation

Interventions

Arginine

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Results Point of Contact

• Title: Dr. Nicholas Kenyon
• Organization: UC Davis

njkenyon@ucdavis.edu

916-734-3564

Study Officials

• Nicholas Kenyon, MD,MS

  Univ. of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 26, 2013
• Study Start: August 1, 2013
• Primary Completion: August 1, 2018
• Study Completion: December 1, 2019
• Last Updated: April 21, 2020
• Results First Posted: April 21, 2020

Record last verified: 2020-04

Locations

US (1)