Beta-glucans for Hospitalised Patients With COVID-19

Beta-glucans as Immune Modulators Amongst Hospitalised Patients With COVID-19: A Pilot Randomised Trial

This randomised trial aims to assess the role of beta1-3 glucan supplementation in improving clinical symptoms and other outcomes amongst hospitalised patients with COVID-19.

Study Overview

• Status: Not yet recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: MC 3x3; Drug: Placebo

Detailed Description

COVID-19 can present as a life-threatening disease characterised by respiratory failure and high circulating levels of inflammatory cytokines. Beta-glucans comprise a heterogeneous group of natural polysaccharides consisting of D-glucose monomers linked by a beta-glycosidic bond. They represent key structural elements of the cell wall and may serve as energy storage in bacteria, fungi including yeast, algae, and plants. In this triple-masked randomised trial, hospitalised patients requiring treatment with supplemental oxygen because of a laboratory-confirmed infection by SARS-CoV-2 will receive supplementation with 1-3 beta-glucans or placebo as part of their standard treatment. The primary endpoint of this trial is the intensity of clinical symptoms as detected by the Wisconsin Upper Respiratory Symptom Survey (WURSS).

Patients requiring mechanical ventilation at baseline will be excluded, as will those with cognitive impairment that precludes the use of clinical assessment scales, patients in which an order to limit therapeutic efforts has been issued, pregnant or breastfeeding women and those who decline to participate in this study. Secondary outcomes will include clinical deterioration requiring admission to an intensive care unit, requirement of high-flow nasal cannula or invasive mechanical ventilation and overall survival. Patients will be followed-up until hospital discharge or up to fifteen days after randomisation. Statistical analyses will be undertaken by a statistician unaware of treatment allocation under the intention-to-treat principle.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Araya; Phone Number: + 56 9 989996955; Email: michaelarayach@gmail.com
• Study Contact Backup: Name: Felipe T Martinez, MD, MSc; Phone Number: +56 32 2573399; Email: felipe.martinez@concentrainvestigacion.cl

Study Locations

• Chile
  • Valparaiso
    • Viña Del Mar, Valparaiso, Chile, 2570017
      • Hospital Gustavo Fricke
      • Contact: Michael Araya; Email: michaelarayach@gmail.com
      • Contact: Alejandra Correa, MD; Email: acorreall@gmail.com
      • Principal Investigator: Roberto A Merino, MD
      • Principal Investigator: Nicolas M Caroca, MD
      • Sub-Investigator: Alejandra V Fernández, RN
      • Sub-Investigator: Cristian Ortega, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult participants with an infection caused by SARS-CoV-2 confirmed with a reverse-transcription polymerase chain reaction (RT-PCR) obtained from a nasopharyngeal swab.

Exclusion Criteria:

• Life expectancy < 6 months
• Currently receiving invasive mechanical ventilation at baseline.
• Cognitive impairment that precludes the use of WURSS or understanding the informed consent form.
• Refusal to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Beta-Glucans; Patients allocated to this arm will receive MC 3x3, an oral supplement containing 25mg of 1,3 beta-Glucans daily for up to three consecutive days.	Drug: MC 3x3; Patients allocated to this arm will receive MC 3x3, an oral supplement containing 25mg of 1,3 beta-Glucans of fungal origin (Trichoderma sp.) daily for up to three consecutive days.
Placebo Comparator: Placebo; Participants allocated to this arm will receive a placebo that will be identical in form to the MC 3x3 pills used the interventional arm. These doses will be scheduled daily and administered orally for up to three consecutive days.	Drug: Placebo; Patients allocated to this arm will receive a matching placebo similar to MC 3x3 pills used in the intervention arm. Placebos will be delivered orally every day for up to three consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom severity	Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score.	WURSS-21 scores calculated 1 day after randomisation
Symptom severity	Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score.	WURSS-21 scores calculated 2 days after randomisation
Symptom severity	Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score.	WURSS-21 scores calculated 3 days after randomisation
Symptom severity	Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score.	WURSS-21 scores calculated 5 days after randomisation
Symptom severity	Symptom severity based on the Wisconsin Upper Respiratory Symptom Survey (WURSS) score.	WURSS-21 scores calculated 7 days after randomisation
Symptom duration	Total time with disease manifestations attributable to COVID-19.	Up to 2 weeks after randomisation or hospital discharge
Clinical recovery	Number of patients without clinical complaints attributable to COVID-19	Seven days after randomisation or up to hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-Reactive protein levels	C-Reactive protein levels measured at various time intervals during the hospitalisation.	This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation.
Absolute lymphocyte count	Absolute lymphocyte counts measured at various time intervals during the hospitalisation.	This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation.
Neutrophil to lymphocyte ratio	Neutrophil to lymphocyte ratios measured at various time intervals during the hospitalisation.	This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation.
Intensive Care Unit Admission	Proportion of patients requiring admission to an intensive care unit in each study group	Up to seven days after randomisation
Invasive mechanical ventilation	Proportion of patients requiring invasive mechanical ventilation in each study group	Up to seven days after randomisation
Survival	Proportion of patients that survived COVID-19 in each study group	Up to seven days after randomisation
Hospital Stay	Total stay within the hospital amongst participants	Until hospital discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events attributable to Beta-Glucan supplementation	Up to seven days after randomisation

Collaborators and Investigators

• Sponsor: Wohlstand Pharmaceutical
• Collaborators: Concentra Educación e Investigación Biomédica
• Investigators: Study Director: Alejandra Correa, MD, Hospital Geriátrico Paz de La Tarde; Principal Investigator: Maria José Ruz, Hospital Gustavo Fricke; Principal Investigator: Mario Reyes, Science & Cash Group SpA; Principal Investigator: Felipe Martinez, MD, MSc, Concentra Investigacion; Principal Investigator: Michael Araya, Hospital Gustavo Fricke

Publications and helpful links

General Publications

• Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS; China Medical Treatment Expert Group for Covid-19. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020 Apr 30;382(18):1708-1720. doi: 10.1056/NEJMoa2002032. Epub 2020 Feb 28.
• Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020 Jun;215:108427. doi: 10.1016/j.clim.2020.108427. Epub 2020 Apr 20.
• Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020 Jul 28;71(15):762-768. doi: 10.1093/cid/ciaa248.
• De Marco Castro E, Calder PC, Roche HM. beta-1,3/1,6-Glucans and Immunity: State of the Art and Future Directions. Mol Nutr Food Res. 2021 Jan;65(1):e1901071. doi: 10.1002/mnfr.201901071. Epub 2020 Apr 27.
• Zimmerman JW, Lindermuth J, Fish PA, Palace GP, Stevenson TT, DeMong DE. A novel carbohydrate-glycosphingolipid interaction between a beta-(1-3)-glucan immunomodulator, PGG-glucan, and lactosylceramide of human leukocytes. J Biol Chem. 1998 Aug 21;273(34):22014-20. doi: 10.1074/jbc.273.34.22014.
• Li B, Allendorf DJ, Hansen R, Marroquin J, Ding C, Cramer DE, Yan J. Yeast beta-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway. J Immunol. 2006 Aug 1;177(3):1661-9. doi: 10.4049/jimmunol.177.3.1661.
• Mah E, Kaden VN, Kelley KM, Liska DJ. Beverage Containing Dispersible Yeast beta-Glucan Decreases Cold/Flu Symptomatic Days After Intense Exercise: A Randomized Controlled Trial. J Diet Suppl. 2020;17(2):200-210. doi: 10.1080/19390211.2018.1495676. Epub 2018 Oct 31.
• Talbott S, Talbott J. Effect of BETA 1, 3/1, 6 GLUCAN on Upper Respiratory Tract Infection Symptoms and Mood State in Marathon Athletes. J Sports Sci Med. 2009 Dec 1;8(4):509-15. eCollection 2009.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 18, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; Survival; Therapy; Mechanical ventilation; Signs and Symptoms; beta-Glucans
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CON-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No