COPD, COPD (Chronic Obstructive Pulmonary Disease), Probiotic, Probiotic Supplement
Conditions
Keywords
COPD, Chronic Obstructive Pulmonary disease, mMRC, dyspnea, CAT, Interleukin-6, Probiotics, probiotic supplement, dietary supplement
Brief summary
The goal of this randomized, placebo controlled, double-blind clinical trial is to find out whether a probiotic supplement can help adults with chronic obstructive pulmonary disease (COPD) breathe better and better control their symptoms. The study will try to answer does taking a probiotic supplement, compare with a placebo, reduce shortness of breath, does it improve daily COPD symptoms or change stool patterns by using validated questionnaires; does it affect lung function or inflammation. The results of this study may contribute to a better understanding of the disease, the application of new therapeutic options, and provide a foundation for future research.
Detailed description
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by persistent symptoms such as shortness of breath, chronic cough, sputum production, and periods of acute worsening. It is also associated with ongoing systemic inflammation, which contributes to symptom severity, impaired lung function, and increased risk of exacerbations. Emerging evidence suggests that the gut-lung axis may play a significant role in this inflammatory process. Probiotics, which help restore a healthy microbial balance and support gut barrier integrity, have been proposed as a potential strategy to modulate inflammation and respiratory symptoms. Several studies have suggested that probiotics may reduce respiratory symptoms, improve lung function and lower systemic inflammation in people with COPD. This randomized study is designed to evaluate whether a probiotic supplement (Saccharomyces boulardii, Lactobacillus plantarum LP 6596, and Lactobacillus plantarum HEAL9) can improve shortness of breath, overall symptom burden, lung function, and selected inflammatory markers in adults with stable COPD compared with placebo. Participants will be recruited from multiple clinical centers and will continue their usual COPD therapy throughout the study period. A total of 60 adult participants with a confirmed diagnosis of COPD, stable disease and baseline dyspnea of mMRC (modified Medical Research Council) ≥ 1 will be randomized to receive either a probiotic supplement or placebo for 16 weeks. They will take either the probiotic supplement or placebo 2 capsules once daily for 16 weeks and will be examined at three clinic visits for symptom questionnaires- mMRC scale of dyspnea, CAT (COPD Assessment Test) and Bristol Stool Scale, blood sampling, and spirometry testing. Between clinic visits, participants will have regular telephone checks every 4 weeks to assess symptoms, adherence to the study product and possible side effects. This trial aims to provide a more comprehensive understanding of how probiotic supplementation may influence dyspnea, quality of life, inflammatory activity, and respiratory function in COPD.
Interventions
DIETARY_SUPPLEMENTProbiotic Capsule
The participants will take two probiotic capsules per day for 16 weeks, containing S. boulardii, Lactobacillus plantarum LP 6596, and Lactobacillus plantarum HEAL9. The product will be coded for blinding purposes.
DIETARY_SUPPLEMENTplacebo capsule
Participants will receive two capsules per day for 16 weeks, a placebo preparation that is identical in composition and form to the probiotic but does not contain an active substance. The product will be coded for blinding purposes.
Sponsors
University Hospital of Split
Abela Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Double-blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with a previously established diagnosis of COPD, regardless of the degree of airflow obstruction on pulmonary function testing. 2. Age over 18 years, regardless of sex. 3. Stable disease without exacerbations during the past two months (8 weeks). 4. Stable disease without changes to maintenance therapy during the past two months (8 weeks). 5. Patients with an mMRC score of 1 or higher. 6. Signed informed consent.
Exclusion criteria
1. patients diagnosed with serious comorbidities such as severe cardiovascular diseases (severe heart failure, acute coronary syndrome, or percutaneous coronary intervention within 6 months, uncontrolled tachy/bradyarrhythmias), patients with severe renal failure and a placed central venous catheter, patients with severe liver damage (Child-Pugh class C), patients with infectious hepatitis or HIV, active bloody diarrhea; 2. patients undergoing active oncological and hematological treatment; 3. patients who have had a stroke within the past 3 months; 4. transplanted patients, including allograft recipients; 5. patients on long-term systemic corticosteroid and immunosuppressive therapy (oral or intravenous form) as well as antifungal therapy, 6. patients who have had a COPD exacerbation within the past two months and are not in a stable condition, 7. patients diagnosed with asthma, 8. patients with a history of lung surgery or serious respiratory diseases other than COPD (active tuberculosis, sarcoidosis, pulmonary fibrosis, severe bronchiectasis, pulmonary aspergillosis, etc.), 9. patients who have recently participated in other clinical trials or have received experimental therapy, 10. patients with a history of severe allergic reactions or hypersensitivity to the components of the probiotic preparation, 11. patients with active alcoholism or drug addiction, 12. patients with severe psychiatric diagnoses or those with significant physical or cognitive limitations that would interfere with following the study protocol, 13. patients who have recently undergone surgery, 14. pregnant or breastfeeding women, 15. patients who have taken any probiotic preparations within one month before the start of the study, 16. patients whose COPD treatment is changed during the course of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mMRC scale of dyspnea | 8 weeks | The primary objective of this study is to assess the degree of change in dyspnea, measured using the validated mMRC (Modified Medical Research Council) questionnaire in patients with COPD eight weeks after administration of the probiotic dietary supplement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAT questionnaire | 8, 16 weeks | To evaluate the effect of probiotic therapy on symptom control and quality of life in COPD patients using the validated CAT (COPD Assessment Test) questionnaire after 4, 8, 12, and 16 weeks of probiotic administration. |
| Bristol stool scale | 8, 16 weeks | To assess the effect of probiotic therapy on stool appearance using the Bristol Stool Scale at baseline and after 8 and 16 weeks of probiotic administration. |
| mMRC | 4,12,16 weeks | To evaluate changes in dyspnea severity on the mMRC scale after 4, 12, and 16 weeks of probiotic administration. |
| IL-6 | 8 weeks | Changes in laboratory-measured IL-6 (interleukin-6) levels at baseline and after 8 weeks of probiotic administration. |
| Complete blood count | 8 and 16 weeks | To investigate the effect of probiotics on changes in concentration of total leukocyte count (×10⁹/L) with differential ((concentration of neutrophil count (×10⁹/L) , eosinophil count (×10⁹/L), monocyte (×10⁹/L) and lymphocyte count (×10⁹/L)) at baseline and after 8 and 16 weeks. |
| Fibrinogen | 8 and 16 weeks | To evaluate changes in serum concentration of fibrinogen (g/L) from baseline and after 8 and 16 weeks of probiotic administration. |
| CRP | 8 and 16 weeks | To evaluate changes in serum concentration of CRP (C-reactive protein) in mg/L from baseline and after 8 and 16 weeks of probiotic administration. |
| Metabolic blood parameters-glucose | 8, 16 weeks | To assess changes in concentration of plasma glucose (mmol/L) measured at baseline and after 8 and 16 weeks of probiotic administration. |
| Metabolic blood parameters-urea | 8, 16 weeks | To assess changes in urea concentration (mmol/L) measured at baseline, 8 weeks, and 16 weeks of probiotic administration. |
| Metabolic blood parameters-creatinine | 8, 16 weeks | To assess changes in creatinine concentration (µmol/L) measured at baseline, 8 weeks, and 16 weeks. |
| Metabolic blood parameters-liver enzymes | 8, 16 weeks | To assess changes in activity of Aspartate Aminotransferase (AST) A (U/L), Alanine Aminotransferase (ALT) (U/L) and Gamma-Glutamyl Transferase (GGT) (U/L) at baseline and after 8 and 16 weeks of probiotic administration. |
| Metabolic blood parameters-electrolytes | 8, 16 weeks | To assess changes in concentration of sodium (mmol/L), potassium (mmol/L), and chloride (mmol/L) at baseline, after 8 and 16 weeks of probiotic administration. |
| Metabolic blood parameters-lipid profile | 8, 16 weeks | To assess changes in concentration of total cholesterol (mmol/L), High-Density Lipoprotein-HDL(mmol/L), Low-Density Lipoprotein-LDL(mmol/L), triglycerides (mmol/L) at baseline, 8 weeks, and 16 weeks of probiotic administration. |
| Lung function | 16 weeks | To evaluate the effect of probiotics on spirometry-derived values: FEV₁% (forced expiratory volume in one second) (L), FVC% (forced vital capacity) (L), and the FEV₁/FVC ratio after bronchodilator testing at baseline and after 16 weeks of probiotic administration . |
| Acute exacerbations | 16 weeks | To investigate the effect of probiotic strains on the incidence of acute exacerbations after 16 weeks. |
| Correlation IL-6 and CRP | 8 weeks | To determine the correlation between IL-6 concentration and CRP after 8 weeks of probiotic administration. |
| Other correlations | 16 weeks | To determine the correlation between CRP concentration and spirometry findings (FEV₁ and the FEV₁/FVC ratio); correlation between fibrinogen levels and spirometry findings (FEV₁ and the FEV₁/FVC ratio); correlation between leukocyte count and spirometry findings (FEV₁ and the FEV₁/FVC ratio) after 16 weeks of probiotic administration. |
| BMI | 16 weeks | To evaluate the effect of probiotic strain administration on changes in body mass index (BMI) after 16 weeks of probiotic administration. |
Countries
Croatia
Outcome results
None listed