Faculty Collaboration Database

A 28-day clinical trial of aerosolized hyaluronan in alpha-1 antiprotease deficiency COPD using desmosine as a surrogate marker for drug efficacy. Respir Med 2021 Jun;182:106402

Date

04/28/2021

Pubmed ID

33906126

DOI

10.1016/j.rmed.2021.106402

Scopus ID

2-s2.0-85104764671 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

INTRODUCTION: A previous 2-week clinical trial of aerosolized hyaluronan (HA) in COPD showed a rapid reduction in lung elastic fiber breakdown, as measured by sputum levels of the unique elastin crosslinks, desmosine and isodesmosine (DID). To further assess the therapeutic efficacy of HA and the utility of DID as surrogate markers for the development of pulmonary emphysema, we have conducted a 28-day randomized, double-blind, placebo-controlled, phase 2 trial of HA involving 27 subjects with alpha-1 antiprotease deficiency COPD.

METHODS: The study drug consisted of a 3 ml inhalation solution containing 0.03% HA with an average molecular weight of 150 kDa that was self-administered twice daily. DID levels were measured in urine, sputum, and plasma using tandem mass spectrometry.

RESULTS: Free urine DID in the HA group showed a significant negative correlation with time between days 14 and 35 (r = -1.0, p = 0.023) and was statistically significantly decreased from baseline at day 35 (15.4 vs 14.2 ng/mg creatinine, p = 0.035). A marked decrease in sputum DID was also seen in the HA group between days 1 and 28 (0.96 vs 0.18 ng/mg protein), but the difference was not significant, possibly due to the small number of adequate specimens. Plasma DID remained unchanged following HA treatment and no significant reductions in urine, sputum, or plasma DID were seen in the placebo group.

CONCLUSIONS: The results support additional clinical trials to further evaluate the therapeutic effect of HA and the use of DID as a real-time marker of drug efficacy.

Author List

Cantor JO, Ma S, Liu X, Campos MA, Strange C, Stocks JM, Devine MS, El Bayadi SG, Lipchik RJ, Sandhaus RA, Turino GM

Author

Randolph J. Lipchik MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Inhalation
Adult
Aerosols
Aged
Biomarkers
Desmosine
Double-Blind Method
Female
Humans
Hyaluronic Acid
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive
Time Factors
Treatment Outcome
alpha 1-Antitrypsin Deficiency