Evidence map›Paper›PMID 32497023›Full record

Trial reportJCI insight2020

l-Arginine supplementation in severe asthma.

Shu-Yi Liao, Megan R Showalter, Angela L Linderholm, Lisa Franzi, Celeste Kivler, Yao Li, Michael R Sa, Zachary A Kons, Oliver Fiehn, Lihong Qi and 2 more

2 registry-linked trialsOpen access · goldAbstract readRandomized Controlled TrialClinical Trial, Phase II
In one paragraph

Trial report in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01841281 phase2completednot on this map

Phase II Study of L-arginine in Severe Asthma Patients Grouped by Exhaled Nitric Oxide Level

TypeinterventionalSponsorNicholas KenyonRan2013 to 2019Enrolled54ConditionsAsthma, InflammationArmsL-Arginine, Placebo
NCT05042024 phase3completednot on this map

Supplementation With L-ornithine Increases Representation Density of CD68+ and CD163+ Macrophages in Human Periodontitis Gingiva and Can Modulate Macrophages Phenotypes. Randomized Controlled Pilot Trial

TypeinterventionalSponsorUkrainian Medical Stomatological AcademyRan2017 to 2018Enrolled75ConditionsPeriodontitisArmsScaling and root planing, Oral L-arginine aspartate administration, Oral L-ornithine aspartate administration
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Changes in FeNO, d-ROMs, and BHJournal of asthma and allergy · 2024
    Article
  9. Amino acid metabolism in health and disease.Signal transduction and targeted therapy · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Arginine Therapy for Lung Diseases.Frontiers in pharmacology · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Shu-Yi LiaoDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, UCD, Sacramento, California, USA.
Megan R ShowalterNIH West Coast Metabolomics Center.
Angela L LinderholmDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, UCD, Sacramento, California, USA.
Lisa FranziDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, UCD, Sacramento, California, USA.
Celeste KivlerDepartment of Respiratory Therapy, and.
Yao LiDepartment of Public Health Sciences, UCD, Davis, California, USA.
Michael R SaNIH West Coast Metabolomics Center.
Zachary A KonsNIH West Coast Metabolomics Center.
Oliver FiehnNIH West Coast Metabolomics Center.
Lihong QiDepartment of Public Health Sciences, UCD, Davis, California, USA.
Amir A ZekiDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, UCD, Sacramento, California, USA.
Nicholas J KenyonDivision of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, UCD, Sacramento, California, USA.
University of California System · USWest Coast University · USDepartment of Public Health · USRespiratory Clinical Trials · AU

Funding

Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Barbara L. Shacklett · 2002 to 2026
$84.9M
UC Davis Clinical and Translational Science CenterUL1TR001860 · NCATS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KENYON, NICHOLAS J., LYLES, COURTNEY REES · 2016 to 2025
$47.3M
UC Davis Environmental Health Sciences Core CenterP30ES023513 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Ameer Taha · 2015 to 2026
$26.0M
West Coast Central Comprehensive Metabolomics Resource Core (WC3MRC)U24DK097154 · NIDDK · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FIEHN, OLIVER · 2012 to 2017
$9.9M
UC Davis CTSC TL1 Administrative Supplement to Recognize Excellence in Diversity, Equity, Inclusion, and Accessibility MentorshipTL1TR001861 · NCATS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MEDICI, VALENTINA · 2016 to 2025
$4.7M
L-arginine as a therapy in severe asthmaR01HL105573 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI KENYON, NICHOLAS J. · 2012 to 2016
$1.9M
The Modulation of Eotaxin Expression by Statins: Implications for Asthma TherapyK08HL114882 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ZEKI, AMIR A. · 2014 to 2016
$435k
NCATS NIH HHS TL1 TR001861NCATS NIH HHS UL1 TR001860NCI NIH HHS P30 CA093373NHLBI NIH HHS K08 HL114882NHLBI NIH HHS R01 HL105573NIDDK NIH HHS U24 DK097154NIEHS NIH HHS P30 ES023513
6 · The paper itself

Abstract

BACKGROUNDDysregulation of l-arginine metabolism has been proposed to occur in patients with severe asthma. The effects of l-arginine supplementation on l-arginine metabolite profiles in these patients are unknown. We hypothesized that individuals with severe asthma with low fractional exhaled nitric oxide (FeNO) would have fewer exacerbations with the addition of l-arginine to their standard asthma medications compared with placebo and would demonstrate the greatest changes in metabolite profiles.METHODSParticipants were enrolled in a single-center, crossover, double-blind l-arginine intervention trial at UCD. Subjects received placebo or l-arginine, dosed orally at 0.05 mg/kg (ideal body weight) twice daily. The primary end point was moderate asthma exacerbations. Longitudinal plasma metabolite levels were measured using mass spectrometry. A linear mixed-effect model with subject-specific intercepts was used for testing treatment effects.RESULTSA cohort of 50 subjects was included in the final analysis. l-Arginine did not significantly decrease asthma exacerbations in the overall cohort. Higher citrulline levels and a lower arginine availability index (AAI) were associated with higher FeNO (P = 0.005 and P = 2.51 × 10-9, respectively). Higher AAI was associated with lower exacerbation events. The eicosanoid prostaglandin H2 (PGH2) and Nα-acetyl-l-arginine were found to be good predictors for differentiating clinical responders and nonresponders.CONCLUSIONSThere was no statistically significant decrease in asthma exacerbations in the overall cohort with l-arginine intervention. PGH2, Nα-acetyl-l-arginine, and the AAI could serve as predictive biomarkers in future clinical trials that intervene in the arginine metabolome.TRIAL REGISTRATIONClinicalTrials.gov NCT01841281.FUNDINGThis study was supported by NIH grants R01HL105573, DK097154, UL1 TR001861, and K08HL114882. Metabolomics analysis was supported in part by a grant from the University of California Tobacco-Related Disease Research Program program (TRDRP).

Indexed as

Dietary SupplementsAdolescentArginineAsthmaCitrullineDouble-Blind MethodExhalationFemaleHumansMaleMiddle AgedNitric OxideArginineCitrullineN-acetyl-L-arginineNitric OxideAsthmaPulmonology

Identifiers

PMID32497023
PMCPMC7406254
OpenAlexW3033654928

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.