Efficacy of L. Plantarum and P. Acidilactici in Adults With SARS-CoV-2 and COVID-19

Study Overview
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Brief Summary
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Clinical research focused to evaluate the effect as coadyuvant of a combination of L. plantarum and P. acidilactici in adults positive for SARS-CoV-2 with mild clinical COVID-19 symptoms. Main objective is to evaluate how this combination of probiotics reduce the risk to progress to moderate or severe COVID and associated advantages such as reduce the risk of death. Adittionnally this RCT is launching to explore the benefits of this combination of strains to modulate fecal microbiome and explore how this correlate with clinical improvement.

Detailed Description
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Randomized controlled trial (RCT) to evaluate safety and efficacy of Lactobacillus plantarum CECT 30292, Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485 y P. acidilactici CECT 7483, one dose a day to reduce the risk of subjects with mild COVID-19 to evolute to moderate or severe disease. As secondary aims this trial is intented to evaluate the effect of this strains combinations to reduce the frequency and severity of gastrointestinal COVID-19 symptoms and lung abnormalities, to reduce the viral load, modulate the levels of IgG/IgM, and positively modify the fecal microbiota. 300 adults, 18 to 60 years, RTq-PCR positive for SARS-CoV-2, with mild COVID-19, and SpO2 > 90%, living in Mexico city (2,200m over the sea level) will be randomized, after sign of informed consent to receive a combintation of Lactobacillus plantarum CECT 30292, Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485 y P. acidilactici CECT 7483 one a day orally or placebo for 30 days. Clinical severity, lung abnormalities (x-rays), viral load, IgG/IgM levels, and fecal microbiome will be evaluated at COVID-19 research center before randomization. Participants will be invited to remain at home and clinical evolution, temperature, SpO2 will be recorder and reported remotely during the 30 days intervention. On days 15 and 30, participants will be invited to return to COVID-19 research center to take samples to evaluate evolution of viral load, IgG/IgM and fecal microbiome. During the 30-days intervention period outcomes such as clinical progression, need of hospitalization, admission to Intensive Care Unit and death will be evaluated

Official Title
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Efficacy and Safety of Lactobacillus Plantarum and Pediococcus Acidilactici as Co-adjuvant Therapy for Reducing the Risk of Severe Disease in Adults With SARS-CoV-2 and Its Modulation of the Fecal Microbiota: A Randomized Clinical Trial

Conditions
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SARS-CoV Infection

Intervention / Treatment
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* Dietary Supplement: Probiotics
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men, >18y to 60 years RTq-PCR to COVID positive Presence of cough, fever, dyspnoea, or headache, onset <= 7 days Mild severity of COVID-19 Peripheral Oxygen Saturation (SpO2) >90% Able to read, understand and sign the informed consent To have at least one family member to collaborate with the follow-up in the clinical findings at beginning and throughout of the study. Exclusion Criteria: Severe Obesity (BMI>40) Uncontrolled Type II diabetes (HbA1C >8.0) Uncontrolled systolic hypertension (>160mmdeHg) Acute pancreatitis Chronic diarrhea or constipation Inflammatory bowel disease Blood clotting disease Immunosuppression derived from Cancer, post-transplantation, auto-immune disease or HIV Severe and active seasonal allergies Pregnancy or lactation Glucose 6P-dehydrogenase deficiency Regular use of probiotic or antibiotic within 2 weeks before entering the trial Severe or uncontrolled Chronic Respiratory Diseases (Asthma, COPD or Cystic Fibrosis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trials. 300 subjects (18-60 years old) will be allocated to receive a combination of Lactobacillus plantarum CECT 30292, Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485, and P. acidilactici CECT 7483 (branch one) or placebo (branch two)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotics<br>Active test product contains four lactic acid bacteria strains with Qualified Presumption of Safety (QPS)status by European Food Safety Authority (EFSA): Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483, with maltodextrin (E1400, qs) as excipient, formulated in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0. Active test product is a food supplement and not an investigational medicinal product | Dietary Supplement: Probiotics<br>* Combination of Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485, and Pediococcus acidilactici CECT 7483<br>|
| Placebo Comparator: Placebo<br>The control study product is identical in packaging and formulation except that Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT7484, Lactobacillus plantarum CECT7485, and Pediococcus acidilactici CECT7483 (probiotic bacteria) are not present. The Control product only contains maltodextrin (E1400, qs) in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0. | Other: Placebo<br>* Combination of maltodextrin (E1400, qs) in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity progression of COVID-19 | Frequency of randomized subjects who progress from mild to moderate or severe COVID-19, or remission, as evaluated by WHO Clinical Progression Scale | 30 days | 
| Stay at ICU | Length of stay at Intensive Care Unit (ICU) | 30 days | 
| Mortality ratio | Mortality ratio for all causes related to COVID-19 | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load | Description of SARS-Cov-2 viral load evaluated by RT-PCR at screening and on days 15 and 30 | 30 days | 
| Lung abnormalities | Frequency of lung abnormalities clasified by severity and measured by x-ray and artificial intelligence | 30 days | 
| Levels of immunoglobulins | Levels of Immunoglobulin G and Immunoglobulin M evaluated on day 15 and 30 | 30 days | 
| Gastrointestinal manifestations, where 0 means good health status and 5 worse status | Frequency and severity of gastrointestinal manifestation evaluated by Gastrointestinal Symptom Rating Scale (GSRS) | 30 days | 
| Fecal microbiome | Changes on fecal microbiome evaluated by 16S analysis on day 1st and 30th | 30 days | 
| Adverse events | Frequency of adverse events reported on dairy report form after randomization and until day 30 | 30 days | 
| Change on Serum Biomarkers | Change on high sensitivity C-reactive protein (hsCRP) and D-Dimer | Days 1st, 15th and 30th after randomization | 
| Duration of Individual Symptoms | Days of fever, cough, myalgia, dyspnea and headache | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, sars-cov-2, covid-19, adults