Improving Quality of Life and Daily Life Activities With Bioarginine in Patients With COPD: a Multicenter, Randomized, Controlled, Proof of Concept Study

• Status: Not yet recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: All

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 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.

Our 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 respiratory symptoms and dyspnea during daily life activities. The secondary objective of this 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, we 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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Milan

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