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

SARS-CoV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04517422
• Other study ID #: ABB-COVID19
• Status: Completed
• Phase: N/A
• Start date: August 19, 2020
• Est. completion date: February 2, 2021

Study information

• Verified date: May 2021
• Source: AB Biotics, SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: February 2, 2021
• Est. primary completion date: February 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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)

Related Conditions & MeSH terms

• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Dietary Supplement:
• Probiotics
Combination of Lactobacillus plantarum CECT30292, Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485, and Pediococcus acidilactici CECT 7483

Other:
• Placebo
Combination of maltodextrin (E1400, qs) in a vegetable hydroxymethylpropyl-cellulose capsule (HPMC) of size 0

Locations

Country	Name	City	State
Mexico	Hospital General Dr. Manuel Gea Gonzalez	Mexico city

Sponsors (4)

Lead Sponsor	Collaborator
AB Biotics, SA	Hospital Angeles del Pedregal, Hospital General Dr. Manuel Gea González, Innovacion y Desarrollo de Estrategias en Salud

Country where clinical trial is conducted

Mexico, 

References & Publications (8)

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. — View Citation

Bottari B, Castellone V, Neviani E. Probiotics and Covid-19. Int J Food Sci Nutr. 2021 May;72(3):293-299. doi: 10.1080/09637486.2020.1807475. Epub 2020 Aug 12. Review. — View 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-CoV — View 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. — View Citation

Klann E, Rich S, Mai V. Gut microbiota and COVID-19: A superfluous diagnostic biomarker or therapeutic target? Clin Infect Dis. 2020 Aug 11. pii: ciaa1191. doi: 10.1093/cid/ciaa1191. [Epub ahead of print] — View Citation

Marcialis MA, Bardanzellu F, Fanos V. Microbiota and Covid-19. Which came first, the chicken or the egg? Clin Infect Dis. 2020 Jul 10. pii: ciaa965. doi: 10.1093/cid/ciaa965. [Epub ahead of print] — View 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. Review. — View Citation

Zuo T, Liu Q, Zhang F, Lui GC, Tso EY, Yeoh YK, Chen Z, Boon SS, Chan FK, Chan PK, Ng SC. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. 2021 Feb;70(2):276-284. doi: 10.1136/gutjnl-2020-322294. Epub 2020 Jul 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Stay at ICU	Length of stay at Intensive Care Unit (ICU)	30 days
Primary	Mortality ratio	Mortality ratio for all causes related to COVID-19	30 days
Secondary	Viral load	Description of SARS-Cov-2 viral load evaluated by RT-PCR at screening and on days 15 and 30	30 days
Secondary	Lung abnormalities	Frequency of lung abnormalities clasified by severity and measured by x-ray and artificial intelligence	30 days
Secondary	Levels of immunoglobulins	Levels of Immunoglobulin G and Immunoglobulin M evaluated on day 15 and 30	30 days
Secondary	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
Secondary	Fecal microbiome	Changes on fecal microbiome evaluated by 16S analysis on day 1st and 30th	30 days
Secondary	Adverse events	Frequency of adverse events reported on dairy report form after randomization and until day 30	30 days
Secondary	Change on Serum Biomarkers	Change on high sensitivity C-reactive protein (hsCRP) and D-Dimer	Days 1st, 15th and 30th after randomization
Secondary	Duration of Individual Symptoms	Days of fever, cough, myalgia, dyspnea and headache	30 days