COPDNCT05412160
Improving Quality of Life and Daily Life Activities With Bioarginine in Patients With COPD
A study testing Arginine in people with COPD and Dyspnea, run by University of Milan at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- COPD, Dyspnea, Argininemia
- What is being tested?
- Arginine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 153 participants
- Where
- 1 siteItaly
- Study dates
- 18 Jan 2023to 30 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- > 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Improving Quality of Life and Daily Life Activities With Bioarginine in Patients With COPD: a Multicenter, Randomized, Controlled, Proof of Concept Study
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.
- Conditions
- COPD, Dyspnea, Argininemia
- Being tested
- Arginine, Placebo
- Keywords
- COPD, Arginine
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Dyspnea, Hyperargininemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArginineDrug
During the first assessment the patients will be randomized to receive BioArginine C™ twice daily on top of chronic inhaled therapy or to continue their chronic Inhaled therapy plus placebo for 6 weeks. The main purpose is to compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group in order to evaluate whether in symptomatic patients with COPD, daily bioarginine on top of chronic inhaled therapy can improve respiratory symptoms and dyspnea. 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.
PlaceboDrug
During the first assessment the patients will be randomized to receive BioArginine C™ twice daily on top of chronic inhaled therapy or to continue their chronic Inhaled therapy plus placebo for 6 weeks. The main purpose is to compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group in order to evaluate whether in symptomatic patients with COPD, daily bioarginine on top of chronic inhaled therapy can improve respiratory symptoms and dyspnea. 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.
| Study group | Role | What they receive |
|---|---|---|
| ARM A - BioArginine receivers | Experimental | Patients will be randomized to receive BioArginine C™ twice daily on top of usual chronic inhaled therapy Receives: Drug: Arginine |
| ARM B - placebo receivers | Placebo comparator | Patients will be randomized to receive placebo twice daily on top of usual chronic inhaled therapy Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group
Patients will undergo the assesment of the Chronic Respitatory Qestionnaire at the time of study erollment and after 6 weeks of treatment with bioarginine or placebo.
The questionnaire contains 20 questions which can be divided into four domains:
- Dyspnoea (5 questions), The dyspnoea domain is "individualised" which means that it is made up of five activities chosen by a patient to cause the greatest shortness of breath. The patient then rates the dyspnoea on these self-selected activities during subsequent administrations of the CRQ.
- Fatigue (4 questions),
- Emotional functioning (7 questions),
- Mastery (4 questions).
- Answers can be scored on a seven point scale ranging from 1 which indicates maximum impairment to 7 which indicates no impairment. The results are expressed as the mean score for each domain and the mean overall score.
- The minimally important difference was found to be an improvement (or deterioration) of 0.5
Measured: 6 weeks
Secondary outcomes (3)
To compare changes in LCADL from baseline and after 6 weeks in the interventional arm compared with the control group
Patients will undergo the assesment of the London Chest Activities of Daily Living at the time of study erollment and after 6 weeks of treatment with bioarginine or placebo.
The LCADL scale is a 15-item tool that measures the effect of dyspnea on routine daily activities. The LCADL provides a total score from 0 to 75 points with higher scores indicating greater limitations. Domain scores include personal care (0-20), domestic activities (0-30), physical activity (0-10), and leisure (0-15). The minimal detectable change (MDC) for the total score is 3.88 or approximately 4 points, 0.89 for personal care, 2.60 for domestic activities, 0.44 for physical activities, and 0.58 for leisure.
The minimal detectable change (MDC) for the total score is 3.88 or approximately 4 points, 0.89 for personal care, 2.60 for domestic activities, 0.44 for physical activities, and 0.58 for leisure.
Measured: 6 weeks
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
Patiens will undergo the Six Minutes Walking Test at study enrolment and after 6 weeks of treatment with bioarginine or placebo.
The 6MWT will be conducted in room air conditions, in a corridor of 30 meters of lenght while the patients has being monitored with a pulsoxymeter that will register the peripheral oxygen saturation and heart right during the test. At the beginning and at the end of the test, Borg Dyspnea Scale (0-10 points), blood pressure and vitals will be registered. The patient will be asked to walk with a sutained pace for six minutes and the distance covered will be recorded. The mMCID of the 6MWT has been definied of 40 meter.
Measured: 6 weeks
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
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2022
- Study start18 Jan 2023
- Primary completion1 Dec 2024
- Study completion30 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pierachille Santus, MD, PhD, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05412160
- Sponsor's protocol ID
- BIOCOPD2022
- Status last verified
- Jun 2025
- First submitted
- 6 Jun 2022
- Last updated
- 4 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 2691207Bisca 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.
PubMed 24531202Garrod 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.
PubMed 10921765
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improving Quality of Life and Daily Life Activities With Bioarginine in Patients With COPD: a Multicenter, Randomized, Controlled, Proof of Concept Study
- ClinicalTrials.gov ID
- NCT05412160
- Acronym / sponsor ID
- BIOCOPD2022
- Conditions
- COPD, Dyspnea, Argininemia
- Keywords
- COPD, Arginine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- 18 Jan 2023 (actual)
- Primary completion
- 1 Dec 2024 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 9 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM A - BioArginine receivers | Experimental | Drug: ArgininePatients will be randomized to receive BioArginine C™ twice daily on top of usual chronic inhaled therapy |
| ARM B - placebo receivers | Placebo comparator | Drug: PlaceboPatients will be randomized to receive placebo twice daily on top of usual chronic inhaled therapy |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- > 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ArginineDuring the first assessment the patients will be randomized to receive BioArginine C™ twice daily on top of chronic inhaled therapy or to continue their chronic Inhaled therapy plus placebo for 6 weeks. The main purpose is to compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group in order to evaluate whether in symptomatic patients with COPD, daily bioarginine on top of chronic inhaled therapy can improve respiratory symptoms and dyspnea. 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. | Drug | ARM A - BioArginine receivers |
| PlaceboDuring the first assessment the patients will be randomized to receive BioArginine C™ twice daily on top of chronic inhaled therapy or to continue their chronic Inhaled therapy plus placebo for 6 weeks. The main purpose is to compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group in order to evaluate whether in symptomatic patients with COPD, daily bioarginine on top of chronic inhaled therapy can improve respiratory symptoms and dyspnea. 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. | Drug | ARM B - placebo receivers |
Primary outcome
To compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group
Time frame: 6 weeks
Patients will undergo the assesment of the Chronic Respitatory Qestionnaire at the time of study erollment and after 6 weeks of treatment with bioarginine or placebo. The questionnaire contains 20 questions which can be divided into four domains: * Dyspnoea (5 questions), The dyspnoea domain is "individualised" which means that it is made up of five activities chosen by a patient to cause the greatest shortness of breath. The patient then rates the dyspnoea on these self-selected activities during subsequent administrations of the CRQ. * Fatigue (4 questions), * Emotional functioning (7 questions), * Mastery (4 questions). * Answers can be scored on a seven point scale ranging from 1 which indicates maximum impairment to 7 which indicates no impairment. The results are expressed as the mean score for each domain and the mean overall score. * The minimally important difference was found to be an improvement (or deterioration) of 0.5
3 secondary outcomes
To compare changes in LCADL from baseline and after 6 weeks in the interventional arm compared with the control group
Time frame: 6 weeks
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
Time frame: 6 weeks
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
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2026.
- Background: PubMed 2691207Jaeschke 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.
- Background: PubMed 24531202Bisca 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.
- Background: PubMed 10921765Garrod 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.
- CRQ questionnaireLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arginine in people with COPD and Dyspnea, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare changes in CRQ from baseline and after 6 weeks in the interventional arm compared with the control group (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05412160, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2026; AzTrials last refreshed its copy on 8 Nov 2026.