Probiotics in COPD: Effects on Symptoms, Lung Function, and Inflammation

N/AEnrolling By InvitationNCT07339280

University Hospital of Split60 enrolled

Overview

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.

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

Probiotic CapsuleDIETARY_SUPPLEMENT

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.

placebo capsuleDIETARY_SUPPLEMENT

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (5)

General Hospital Karlovac

Karlovac, Croatia

University Hospital Split

Split, Croatia

General Hospital Sibenik

Šibenik, Croatia

General Hospital Vinkovci

Vinkovci, Croatia

University Hospital Centre Sestre milosrdnice

Zagreb, Croatia

Outcomes

Primary Outcomes

mMRC scale of dyspnea

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.

Time frame: 8 weeks

Secondary Outcomes

CAT questionnaire

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.

Time frame: 8, 16 weeks

Bristol stool scale

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.

Time frame: 8, 16 weeks

mMRC

To evaluate changes in dyspnea severity on the mMRC scale after 4, 12, and 16 weeks of probiotic administration.

Time frame: 4,12,16 weeks

IL-6

Changes in laboratory-measured IL-6 (interleukin-6) levels at baseline and after 8 weeks of probiotic administration.

Time frame: 8 weeks

Complete blood count

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.

Time frame: 8 and 16 weeks

Fibrinogen

To evaluate changes in serum concentration of fibrinogen (g/L) from baseline and after 8 and 16 weeks of probiotic administration.

Time frame: 8 and 16 weeks

CRP

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.

Time frame: 8 and 16 weeks

Metabolic blood parameters-glucose

To assess changes in concentration of plasma glucose (mmol/L) measured at baseline and after 8 and 16 weeks of probiotic administration.

Time frame: 8, 16 weeks

Metabolic blood parameters-urea

To assess changes in urea concentration (mmol/L) measured at baseline, 8 weeks, and 16 weeks of probiotic administration.

Time frame: 8, 16 weeks

Metabolic blood parameters-creatinine

To assess changes in creatinine concentration (µmol/L) measured at baseline, 8 weeks, and 16 weeks.

Time frame: 8, 16 weeks

Metabolic blood parameters-liver enzymes

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.

Time frame: 8, 16 weeks

Metabolic blood parameters-electrolytes

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.

Time frame: 8, 16 weeks

Metabolic blood parameters-lipid profile

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.

Time frame: 8, 16 weeks

Lung function

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 .

Time frame: 16 weeks

Acute exacerbations

To investigate the effect of probiotic strains on the incidence of acute exacerbations after 16 weeks.

Time frame: 16 weeks

Correlation IL-6 and CRP

To determine the correlation between IL-6 concentration and CRP after 8 weeks of probiotic administration.

Time frame: 8 weeks

Other correlations

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.

Time frame: 16 weeks

BMI

To evaluate the effect of probiotic strain administration on changes in body mass index (BMI) after 16 weeks of probiotic administration.

Time frame: 16 weeks

Probiotics in COPD: Effects on Symptoms, Lung Function, and Inflammation

Overview

Conditions

Interventions

Eligibility

Locations (5)

Outcomes

Primary Outcomes

Secondary Outcomes