Clinical trial NCT05465798: Beta-glucans for Hospitalised Patients With COVID-19
Official title: Beta-glucans as Immune Modulators Amongst Hospitalised Patients With COVID-19: A Pilot Randomised Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
Keywords: beta-Glucans
Therapy
Signs and Symptoms
Mechanical ventilation
Inflammation
Survival
Lead sponsor: Wohlstand Pharmaceutical
Sponsor class: INDUSTRY
Collaborators: name: Concentra Educación e Investigación Biomédica
First posted: 2022-07-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible participants will be randomised to receive either beta-glucan supplements or placebo for up to three days.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Symptom severity
timeFrame: WURSS-21 scores calculated 1 day after randomisation
measure: Symptom severity
timeFrame: WURSS-21 scores calculated 2 days after randomisation
measure: Symptom severity
timeFrame: WURSS-21 scores calculated 3 days after randomisation
measure: Symptom severity
timeFrame: WURSS-21 scores calculated 5 days after randomisation
measure: Symptom severity
timeFrame: WURSS-21 scores calculated 7 days after randomisation
measure: Symptom duration
timeFrame: Up to 2 weeks after randomisation or hospital discharge
measure: Clinical recovery
timeFrame: Seven days after randomisation or up to hospital discharge
Secondary outcomes:
measure: C-Reactive protein levels
timeFrame: This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation.
measure: Absolute lymphocyte count
timeFrame: This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation.
measure: Neutrophil to lymphocyte ratio
timeFrame: This laboratory exam will be measured on days 1, 3, 5 and 7 after randomisation.
measure: Intensive Care Unit Admission
timeFrame: Up to seven days after randomisation
measure: Invasive mechanical ventilation
timeFrame: Up to seven days after randomisation
measure: Survival
timeFrame: Up to seven days after randomisation
measure: Hospital Stay
timeFrame: Until hospital discharge
Other outcomes:
measure: Adverse events
timeFrame: Up to seven days after randomisation
Locations:
city: Viña Del Mar
country: Chile
facility: Hospital Gustavo Fricke
state: Valparaiso
Study officials:
affiliation: Hospital Geriátrico Paz de La Tarde
name: Alejandra Correa, MD
role: STUDY_DIRECTOR
affiliation: Hospital Gustavo Fricke
name: Maria José Ruz
role: PRINCIPAL_INVESTIGATOR
affiliation: Science & Cash Group SpA
name: Mario Reyes
role: PRINCIPAL_INVESTIGATOR
affiliation: Concentra Investigacion
name: Felipe Martinez, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Gustavo Fricke
name: Michael Araya
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.