Effects of L-arginine and Liposomial Vitamin C on Severe Copd Patients Undergoing Pulmonary Rehabilitation.

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06439875
• Other study ID #: CTSM109-23
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 1, 2024
• Est. completion date: July 1, 2025

Study information

• Verified date: April 2024
• Source: Istituti Clinici Scientifici Maugeri SpA
• Contact: Mauro Maniscalco
• Phone: +39 0824909350
• Email: mauro.maniscalco[@]icsmaugeri.it
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 indicators related to endothelial function, potentially mitigating the cardiovascular (CV) disease burden in this clinical context.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 102
• Est. completion date: July 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

Inclusion criteria:

• 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.

Exclusion criteria:

• 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;

• 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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Dietary Supplement:
• effect of L-arginine and liposomial vitamin C on pulmonary rehabilitation
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

Other:
• placebo
Patients in this arm will undergo multidisciplinary intensive pulmonary rehabilitation without any dietary supplementation.

Locations

Country	Name	City	State
Italy	Istituti Clinici Scientifici Maugeri	Telese Terme	Benevento

Sponsors (1)

Lead Sponsor	Collaborator
Istituti Clinici Scientifici Maugeri SpA

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary	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).	at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary	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.	at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary	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.	at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary	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.	at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary	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.	at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary	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).	at baseline and after 28 days of intensive pulmonary rehabilitation
Secondary	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).	at baseline and after 28 days of intensive pulmonary rehabilitation