Clinical trial NCT04517422: Efficacy of L. Plantarum and P. Acidilactici in Adults With SARS-CoV-2 and COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: SARS-CoV Infection
Keywords: probiotics
sars-cov-2
covid-19
adults
Lead sponsor: AB Biotics, SA
Sponsor class: INDUSTRY
Collaborators: name: Innovacion y Desarrollo de Estrategias en Salud
name: Hospital General Dr. Manuel Gea González
name: Hospital Angeles del Pedregal
First posted: 2020-08-18
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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)
Primary purpose: OTHER

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Severity progression of COVID-19
timeFrame: 30 days
measure: Stay at ICU
timeFrame: 30 days
measure: Mortality ratio
timeFrame: 30 days
Secondary outcomes:
measure: Viral load
timeFrame: 30 days
measure: Lung abnormalities
timeFrame: 30 days
measure: Levels of immunoglobulins
timeFrame: 30 days
measure: Gastrointestinal manifestations, where 0 means good health status and 5 worse status
timeFrame: 30 days
measure: Fecal microbiome
timeFrame: 30 days
measure: Adverse events
timeFrame: 30 days
measure: Change on Serum Biomarkers
timeFrame: Days 1st, 15th and 30th after randomization
measure: Duration of Individual Symptoms
timeFrame: 30 days
Other outcomes:
Locations:
city: Mexico city
country: Mexico
facility: Hospital General Dr. Manuel Gea Gonzalez
Study officials:
References:
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citation: d'Ettorre G, Ceccarelli G, Marazzato M, Campagna G, Pinacchio C, Alessandri F, Ruberto F, Rossi G, Celani L, Scagnolari C, Mastropietro C, Trinchieri V, Recchia GE, Mauro V, Antonelli G, Pugliese F, Mastroianni CM. Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19. Front Med (Lausanne). 2020 Jul 7;7:389. doi: 10.3389/fmed.2020.00389. eCollection 2020.
citation: De Maio F, Posteraro B, Ponziani FR, Cattani P, Gasbarrini A, Sanguinetti M. Nasopharyngeal Microbiota Profiling of SARS-CoV-2 Infected Patients. Biol Proced Online. 2020 Jul 25;22:18. doi: 10.1186/s12575-020-00131-7. eCollection 2020.
citation: Villena J, Kitazawa H. The Modulation of Mucosal Antiviral Immunity by Immunobiotics: Could They Offer Any Benefit in the SARS-CoV-2 Pandemic? Front Physiol. 2020 Jun 16;11:699. doi: 10.3389/fphys.2020.00699. eCollection 2020.
citation: Marcialis MA, Bardanzellu F, Fanos V. Microbiota and Coronavirus Disease 2019. Which Came First, the Chicken or the Egg? Clin Infect Dis. 2021 Jun 15;72(12):2245-2246. doi: 10.1093/cid/ciaa965. No abstract available.
citation: Aktas B, Aslim B. Gut-lung axis and dysbiosis in COVID-19. Turk J Biol. 2020 Jun 21;44(3):265-272. doi: 10.3906/biy-2005-102. eCollection 2020.