Chronic Obstructive Pulmonary DiseaseNCT06439875
Effects of L-arginine and Liposomial Vitamin C on Severe Copd Patients Undergoing Pulmonary Rehabilitation.
A study testing effect of L-arginine and liposomial vitamin C on pulmonary rehabilitation in people with Chronic Obstructive Pulmonary Disease and Respiratory Failure, run by Istituti Clinici Scientifici Maugeri SpA at 3 sites in Italy.
Trial summary
The hypothesis that is being tested is that the supplementation of L-arginine plus Vitamin C to multidisciplinary pulmonary rehabilitation (PR) in patients with a previous diagnosis of chronic obstructive pulmonary disease (COPD) and chronic respiratory failure can have a favorable influence on fatigue and on clinical… Read more about this study
- Who is it for?
- Ages 40 to 90 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease, Respiratory Failure
- What is being tested?
- effect of L-arginine and liposomial vitamin C on pulmonary rehabilitation
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 3 sitesItaly
- Study dates
- 16 Jul 2024to 9 Mar 2026
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- COPD patients of both sexes complicated by respiratory failure (PaO2 inferior to 60 mmHg while breathing room air)
- aged between 40 and 90 years selected from the inpatient/outpatient population admitted to perform a PR program in 12 Italian rehabilitation hospitals.
Who cannot join
- consuming any ergogenic supplement in the last 2 months;
- severe acute exacerbations in the 3 months before enrolment;
- clinical instability (pH inferior to 7.35, hemodynamic instability, tachypnea at rest);
- lung restrictive diseases;
- primitive pulmonary hypertension;
- recent lung thromboembolic events;
Show all 13Show fewer
- orthopaedic clinical conditions interfering with exercise;
- coronary heart disease;
- cardiac failure with reduced ejection fraction;
- major cardiac arrhythmias;
- neuromuscular diseases;
- mini mental state examination (MMSE) <24;
- any prior or current medical problem that would limit the subject participation
Trial locations and contacts
3 sites in 1 country.
Italy3 sites
Istituti Clinici Scientifici Maugeri IRCCS
Bari, 70124
Istituti Clinici Scientifici Maugeri IRCCS
Lumezzane, Brescia, 25065
Istituti Clinici Scientifici Maugeri Irccs
Telese Terme, Benevento, 82037
About this study
Official title: Effects of the Association of L-arginine and Liposomal Vitamin C on Fatigue in COPD Patients With Chronic Respiratory Failure After Rehabilitation Intervention
The hypothesis that is being tested is that the supplementation of L-arginine plus Vitamin C to multidisciplinary pulmonary rehabilitation (PR) in patients with a previous diagnosis of chronic obstructive pulmonary disease (COPD) and chronic respiratory failure can have a favorable influence on fatigue and on clinical indicators related to endothelial function, potentially mitigating the cardiovascular (CV) disease burden in this clinical context.
Read the detailed description
The primary objective of this project is to assess the effects of L-arginine plus Vitamin C supplementation on the physical outcomes in a group of COPD patients with chronic respiratory failure who underwent a 28-day PR program.
Eligible participants will be randomized using a random number generator in a 1:1 ratio to receive a twice-daily oral supplementation with either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C (Bioarginina® C, Farmaceutici Damor, Naples, Italy) or a placebo for 28 days. Vials containing the active supplement or the placebo will be supplied by Farmaceutici Damor and will be made indistinguishable in appearance. All patients will undergo an intensive multidisciplinary PR program based on endurance and strength training. The main outcome of the study is the fatigue severity scale (FSS) total score after rehabilitation. Secondary outcomes include: 6-minute walking distance, forced expiratory volume in the first second (FEV1), COPD assessment test (CAT) score, endothelial function assessed through flow-mediated dilation (FMD), and muscular strength assessed through handgrip measurement.
Anthropometric, clinical, and functional characteristics of the study participants will be reported as mean ± standard deviation (SD) or median (interquartile range, IQR) for continuous variables and as absolute values (percentages) for categorical variables. Changes from baseline for continuous variables will be expressed as deltas (values at 28 days minus the values at baseline), and differences between the interventional groups will be evaluated using the Student's t-test for normally distributed variables or the Mann-Whitney U test for skewed variables.
- Being tested
- effect of L-arginine and liposomial vitamin C on pulmonary rehabilitation, placebo
- Keywords
- COPD, pulmonary rehabilitation, L-arginine, fatigue, respiratory failure
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Respiratory Insufficiency, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
effect of L-arginine and liposomial vitamin C on pulmonary rehabilitationDietary supplement
Patients with a certified diagnosis of COPD and chronic respiratory failure will be randomized in a 1:1 ratio into the interventional arm or the placebo controller arm. All patients will undergo multidisciplinary intensive pulmonary rehabilitation for 28 days. The patients in the interventional group will receive a twice-daily oral supplementation with either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C
placeboOther
Patients in this arm will undergo multidisciplinary intensive pulmonary rehabilitation without any dietary supplementation.
| Study group | Role | What they receive |
|---|---|---|
| L-arginine (arm 1) | Experimental | Participants in this arm of the study will have an oral supplementation of l-arginine and liposomial vitamin C on a daily basis for 28 days. Receives: Dietary Supplement: effect of L-arginine and liposomial vitamin C on pulmonary rehabilitation |
| Placebo (arm 2) | Placebo comparator | This arm will be given a placebo comparator on a daily basis for 28 days. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue Severity Scale
The Fatigue Severity Scale (FSS) is a 9-item scale that measures the severity of fatigue and how much it affects the person's activities and lifestyle in patients with a variety of disorders. The items are scored on a 7 point scale with 1=strongly disagree and 7=strongly agree. The minimum score=9 and maximum score possible=63. Higher the score=greater fatigue severity. More common way of scoring: mean of all the scores with minimum score being 1 and maximum score being 7. Mean (SD) FSS scores for healthy individuals; 2.3 (0.7). Cut-off score of 4 or more considered indicative of problematic fatigue.
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary outcomes (7)
Six minute walking test (6MWT)
The six minute walking test (6MWT) is a strong predictor of survival and outcome in PR. The patient is asked to walk on a flat surface for six minutes. The total distance walked, peripheral saturation, heart rate, dyspnea and muscular fatigue are assessed before starting the test and at the end. The distance walked varies with age and might be affected by non-respiratory diseases such as musculoscheletal and cardiovascular diseases. A distance walked inferior to the 80% of the theoretical distance is considered to be abnormal, as well as the presence of desaturations defined as a peripheral oxygen saturation < 90%. Dyspnea and fatigue are assessed through the modified Borg's scale, which ranges from 0 (= no symptom) to 10 (the most intense sensation imaginable).
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
Sit to stand test (STST)
The participant is coached to perform as many full stands as possible within 30 seconds, starting from and returning to a complete sitting position.
It is possible to assess a wide variety of ability levels with scores ranging from 0 for those who can not complete one stand to a score greater than 20 for more fit individuals.
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
COPD Assessment Test (CAT)
CAT is designed to measure the impact of COPD on a person's life, and how this changes over time.
CAT explores eight different domains, and for each one the participant may indicate a score ranging from 0 to 5. A score of 0 means that there is no impairment in that area. A score of 5 means severe impairment.The overall score will therefore range from 0 to 40. Higher scores indicate that COPD has a greater impact on the patient's overall health and well-being.
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
Medical Research Council (MRC) for dyspnea test
MRC uses to assess the degree of baseline functional disability due to dyspnoea. It ranges from 0 to 4. A value = 0 indicates no significant dyspnea. A value = 1 indicates dyspnea ony for heavy efforts, A value = 2 indicates dyspnea for moderate efforts. A value = 3 indicates dyspnea for mild efforts. A value = 4 indicates dyspnea at rest.
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
Flow-mediated dilation (FMD);
FMD evaluates the alterations of the diameter of the brachial artery in response to an induced ischemic stimulus. FMD has been widely used in clinical research and allows the studying of the influence of diseases and treatment interventions on endothelial function.
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
Fractional exhaled nitric oxide (FeNO)
Fractional exhaled nitric oxide (FeNO) is an endogenous gaseous molecule which can be measured in human breath. Higher FeNO values have been linked airway inflammation. A cut-off of 25 parts per billion (ppb) has been suggested in order to discriminate between a normal exam (FeNO < 25 ppb) and an altered one (FeNO > or = 25 ppb).
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
Muscle Strength
Muscle strength will be measured with a handgrip device, which consists of a handle-shaped dynamometer which is able to calculate the handgrip's strength (expressed in Newton units).
Measured: at baseline and after 28 days of intensive pulmonary rehabilitation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2024
- Study start16 Jul 2024
- Primary completion16 Feb 2026
- Study completion9 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Istituti Clinici Scientifici Maugeri SpAThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpA
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera dei Colli, Fondazione Don Carlo Gnocchi ETS
- Responsible party
- Sponsor
- Investigators
- mauro maniscalco, Principal investigator, IRCCS Maugeri Telese
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06439875
- Sponsor's protocol ID
- CTSM109-23
- Status last verified
- Mar 2026
- First submitted
- 28 May 2024
- Last updated
- 25 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Maniscalco M, Candia C, Fiorentino G, Bianchi LNC, Fagetti L, Forlani S, La Piana GE, Misuraca C, Vigna M, Buraschi R, Carone M, Trimarco V, Vitacca M; Arginine Study Investigators. Targeting fatigue in COPD with chronic respiratory failure undergoing pulmonary rehabilitation: a multicentre, randomised, placebo-controlled trial of L-arginine/liposomal vitamin C. Thorax. 2026 Sep 18:thorax-2026-225106. doi: 10.1136/thorax-2026-225106. Online ahead of print.
PubMed 42760127
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of the Association of L-arginine and Liposomal Vitamin C on Fatigue in COPD Patients With Chronic Respiratory Failure After Rehabilitation Intervention
- ClinicalTrials.gov ID
- NCT06439875
- Acronym / sponsor ID
- CTSM109-23
- Keywords
- COPD, pulmonary rehabilitation, L-arginine, fatigue, respiratory failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpAUniversity, hospital or other
- Collaborators
- Azienda Ospedaliera dei Colli, Fondazione Don Carlo Gnocchi ETS
- Study start
- 16 Jul 2024 (actual)
- Primary completion
- 16 Feb 2026 (actual)
- Study completion
- 9 Mar 2026 (actual)
- First posted
- 3 Jun 2024 (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.
The hypothesis that is being tested is that the supplementation of L-arginine plus Vitamin C to multidisciplinary pulmonary rehabilitation (PR) in patients with a previous diagnosis of chronic obstructive pulmonary disease (COPD) and chronic respiratory failure can have a favorable influence on fatigue and on clinical indicators related to endothelial function, potentially mitigating the cardiovascular (CV) disease burden in this clinical context.
Detailed description
The primary objective of this project is to assess the effects of L-arginine plus Vitamin C supplementation on the physical outcomes in a group of COPD patients with chronic respiratory failure who underwent a 28-day PR program.
Eligible participants will be randomized using a random number generator in a 1:1 ratio to receive a twice-daily oral supplementation with either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C (Bioarginina® C, Farmaceutici Damor, Naples, Italy) or a placebo for 28 days. Vials containing the active supplement or the placebo will be supplied by Farmaceutici Damor and will be made indistinguishable in appearance. All patients will undergo an intensive multidisciplinary PR program based on endurance and strength training. The main outcome of the study is the fatigue severity scale (FSS) total score after rehabilitation. Secondary outcomes include: 6-minute walking distance, forced expiratory volume in the first second (FEV1), COPD assessment test (CAT) score, endothelial function assessed through flow-mediated dilation (FMD), and muscular strength assessed through handgrip measurement.
Anthropometric, clinical, and functional characteristics of the study participants will be reported as mean ± standard deviation (SD) or median (interquartile range, IQR) for continuous variables and as absolute values (percentages) for categorical variables. Changes from baseline for continuous variables will be expressed as deltas (values at 28 days minus the values at baseline), and differences between the interventional groups will be evaluated using the Student's t-test for normally distributed variables or the Mann-Whitney U test for skewed variables.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-arginine (arm 1) | Experimental | Dietary Supplement: effect of L-arginine and liposomial vitamin C on pulmonary rehabilitationParticipants in this arm of the study will have an oral supplementation of l-arginine and liposomial vitamin C on a daily basis for 28 days. |
| Placebo (arm 2) | Placebo comparator | Other: placeboThis arm will be given a placebo comparator on a daily basis for 28 days. |
Who may qualify
- Ages
- 40 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- COPD patients of both sexes complicated by respiratory failure (PaO2 inferior to 60 mmHg while breathing room air)
- aged between 40 and 90 years selected from the inpatient/outpatient population admitted to perform a PR program in 12 Italian rehabilitation hospitals.
Key exclusion criteria (13 listed)
- consuming any ergogenic supplement in the last 2 months;
- severe acute exacerbations in the 3 months before enrolment;
- clinical instability (pH inferior to 7.35, hemodynamic instability, tachypnea at rest);
- lung restrictive diseases;
- primitive pulmonary hypertension;
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 |
|---|---|---|
| effect of L-arginine and liposomial vitamin C on pulmonary rehabilitationPatients with a certified diagnosis of COPD and chronic respiratory failure will be randomized in a 1:1 ratio into the interventional arm or the placebo controller arm. All patients will undergo multidisciplinary intensive pulmonary rehabilitation for 28 days. The patients in the interventional group will receive a twice-daily oral supplementation with either a combination of 1.66 g l-arginine plus 500 mg liposomal vitamin C | Dietary supplement | L-arginine (arm 1) |
| placeboPatients in this arm will undergo multidisciplinary intensive pulmonary rehabilitation without any dietary supplementation. | Other | Placebo (arm 2) |
Primary outcome
Fatigue Severity Scale
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
The Fatigue Severity Scale (FSS) is a 9-item scale that measures the severity of fatigue and how much it affects the person's activities and lifestyle in patients with a variety of disorders. The items are scored on a 7 point scale with 1=strongly disagree and 7=strongly agree. The minimum score=9 and maximum score possible=63. Higher the score=greater fatigue severity. More common way of scoring: mean of all the scores with minimum score being 1 and maximum score being 7. Mean (SD) FSS scores for healthy individuals; 2.3 (0.7). Cut-off score of 4 or more considered indicative of problematic fatigue.
7 secondary outcomes
Six minute walking test (6MWT)
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
Sit to stand test (STST)
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
COPD Assessment Test (CAT)
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
Medical Research Council (MRC) for dyspnea test
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
Flow-mediated dilation (FMD);
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
Fractional exhaled nitric oxide (FeNO)
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
Muscle Strength
Time frame: at baseline and after 28 days of intensive pulmonary rehabilitation
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 25 Mar 2026.
- Derived from this study: PubMed 42760127Maniscalco M, Candia C, Fiorentino G, Bianchi LNC, Fagetti L, Forlani S, La Piana GE, Misuraca C, Vigna M, Buraschi R, Carone M, Trimarco V, Vitacca M; Arginine Study Investigators. Targeting fatigue in COPD with chronic respiratory failure undergoing pulmonary rehabilitation: a multicentre, randomised, placebo-controlled trial of L-arginine/liposomal vitamin C. Thorax. 2026 Sep 18:thorax-2026-225106. doi: 10.1136/thorax-2026-225106. Online ahead of print.
- Individual participant dataSharing planned: No
Related trials for Chronic Obstructive Pulmonary Disease
Active, not recruiting
Symptoms and Functions in Patients With COPD and Chronic Bronchitis Switching From CIG to THS
COPD, Smoking
Not yet recruitingPhase 2/3
An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Not yet recruiting
The Aim of the Study is to Decipher the Alterations in Signalling Pathways of Skeletal Muscle Stem Cells (Satellite Cells (SCs)) in Individuals With COPD, as Well as to Examine the Effect of Exercise Training on SCs.
COPD (Chronic Obstructive Pulmonary Disease), Sarcopenia in Elderly
Not yet recruitingPhase 2
Study of Treprostinil Administered Via Soft Mist Inhaler (SMI) in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Belumosudil Compared With Best Available Therapy in Participants Aged 12 Years or Older With Chronic Graft-versus-host Disease
Chronic Graft Versus Host Disease
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.
mauro maniscalco principal investigator
IRCCS Maugeri Telese
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing effect of L-arginine and liposomial vitamin C on pulmonary rehabilitation in people with Chronic Obstructive Pulmonary Disease and Respiratory Failure, run by Istituti Clinici Scientifici Maugeri SpA at 3 sites 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 2 inclusion and 13 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 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Fatigue Severity Scale (time frame: at baseline and after 28 days of intensive pulmonary rehabilitation). 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 NCT06439875, which also lists 1 linked publication.
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 25 Mar 2026.