Clinical trial NCT05412160: Improving Quality of Life and Daily Life Activities With Bioarginine in Patients With COPD
Official title: Improving Quality of Life and Daily Life Activities With Bioarginine in Patients With COPD: a Multicenter, Randomized, Controlled, Proof of Concept Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: COPD
Dyspnea
Argininemia
Keywords: COPD
Arginine
Lead sponsor: University of Milan
Sponsor class: OTHER
First posted: 2022-06-09
Enrollment: 152
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Different studies have suggested that COPD is associated with elevated alveolar NO and increased expression of NOS2 in alveolar walls, small airway epithelium and vascular smooth muscle. Furthermore, arginase activity in COPD is shown to correlate inversely with total NO metabolite in sputum and with pre- and post- bronchodilator FEV1; at the same time ADMA levels in serum is shown to be correlated with airway resistance and ADMA in COPD airways was documented to be able to shift the L-arginine metabolism towards the arginase pathway. As demonstrated in a guinea pig model, the arginase inhibition can shift the L-ornitine: L-citrulline ratio towards L-citrulline, preventing neutrophilia, mucus hypersecretion and collagen synthesis. Thus, increasing substrate availability for NOS by arginase inhibition or supplementation of L-arginine or L-citrulline or a combination thereof, may represent a window of opportunity in patients with COPD.

The present study was constructed in order to investigate as a primary objective whether in symptomatic patients with COPD, daily bioarginine on top of chronic inhaled therapy can improve patients' respiratory symptoms and dyspnea during daily life activities. The secondary objective of the study is to determine whether there is any correlation between improvement in respiratory symptoms and distance walked at the 6MWT and lung function parameters. In order to do so, the investigators designed a multi center, interventional, prospective, randomized, controlled vs placebo, proof of concept study: COPD patients will be randomized to receive BioArginine twice daily on top of chronic inhaled therapy or to continue their chronic Inhaled therapy plus placebo for 6 weeks. In order to evaluate the impact on respiratory symptoms and dyspnea the CRQ (Chronic Respiratory disease Questionnaire) and the LCADL (London Chest Activities of daily Living) Scale, as well as the 6MWT, will be used.


Eligibility criteria: Inclusion Criteria:

* \> 40 years old
* Smoke history \>10 pack years (PYs)
* Forced expiratory volume (FEV1 70-40% predicted)
* COPD Assessment Test score \>= 10
* Stable Inhaled therapy in the three months prior to study enrollment

Exclusion Criteria:

* Exacerbations in the three months prior to study enrolment
* Dementia and inability to perform study test bundles
* Interstitial lung disease
* History of asthma
* Patients unable to perform a 6MWT or necessitating a walker to ambulate
* Long term oxygen therapy (excluding patients on nocturnal O2 therapy)
* Patients enrolled In pulmonary rehabilitation programs during the study or that have completed a pulmonary rehabilitation program in the 6 months before study enrollment

Primary outcomes:
measure: To compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group
timeFrame: 6 weeks
Secondary outcomes:
measure: To compare changes in LCADL from baseline and after 6 weeks in the interventional arm compared with the control group
timeFrame: 6 weeks
measure: To compare changes in the distance covered during the 6MWT from baseline and after 6 weeks in the interventional arm compared with the control group
timeFrame: 6 weeks
measure: To compare changes in the dyspnea domain of the CRQ from baseline and after 6 weeks in the interventional arm compared with the control group
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Milan
country: Italy
facility: L. Sacco Hospital
Study officials:
References:
citation: Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the minimal clinically important difference. Control Clin Trials. 1989 Dec;10(4):407-15. doi: 10.1016/0197-2456(89)90005-6.
citation: Bisca GW, Proenca M, Salomao A, Hernandes NA, Pitta F. Minimal detectable change of the London chest activity of daily living scale in patients with COPD. J Cardiopulm Rehabil Prev. 2014 May-Jun;34(3):213-6. doi: 10.1097/HCR.0000000000000047.
citation: Garrod R, Bestall JC, Paul EA, Wedzicha JA, Jones PW. Development and validation of a standardized measure of activity of daily living in patients with severe COPD: the London Chest Activity of Daily Living scale (LCADL). Respir Med. 2000 Jun;94(6):589-96. doi: 10.1053/rmed.2000.0786.