Clinical trial NCT04404218: The Açaí Berry COVID-19 Anti-Inflammation Trial
Official title: Randomized Clinical Trial of Açaí Palm Berry Extract as an Intervention in Patients Diagnosed With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID
Keywords: açaí berry
COVID
community care patients
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: University of Toronto
First posted: 2020-05-27
Enrollment: 480
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, double-blinded, placebo-controlled, randomized, multicentre clinical trial
Primary purpose: TREATMENT

Brief summary: The Açaí trial will be testing if the açaí berry extract, a safe natural product with anti-inflammatory properties, can be used as a treatment option in adult patients with COVID-19 in the community.

Detailed description: The current COVID-19 pandemic is caused by the novel coronavirus (SARS-Cov-2). The virus origins have been studied and evidence so far suggests it originates in bats, with spread to humans likely mediated by an intermediate mammalian. Bats have a dampened Nod-like receptor family, pyrin-containing 3 (NLRP3)-mediated inflammation. Dampening NLRP3-mediated inflammation has been associated with the asymptotic viral status, therefore it is plausible that the pathogenic inflammatory response of SARS-CoV-2 might be associated with activation of NLRP3 inflammasome. Data show that the natural extract of Açaí Palm Berry (Euterpe oleracea Mart.) is a potent inhibitor of NLRP3. This is a safe, inexpensive, and readily available natural health supplement which could be a rapid response treatment intervention for patients with COVID-19.

Our primary objective is to establish whether açai palm berry extract (Euterpe oleracea), given to community-dwelling adult patients diagnosed with COVID-19, compared to placebo, improves outcomes over 30 days on the 7-point ordinal scale described by Cao et al, and which is being used widely in COVID-19 trials with the aim of harmonizing endpoints. This study will be a prospective, double-blinded, placebo-controlled, randomized, multicentre clinical trial of Açaí Palm Berry extract in adult patients tested positive for SARS-Cov-2 in the last 7 days and that are currently being treated in the outpatient setting. The intervention group will receive 3 capsules of 520mg (one capsule every eight hours) of Acai Palm Berry extract (Nature's Way, NPN80038874) for 30 days. The non-intervention group will receive placebo pills, on top of standard clinical care. Our main endpoint will be the 7-point ordinal scale.

This project has the benefit of offering a safe and widely used natural extract as a potential treatment strategy to decrease inflammation and improve disease outcomes in patients with COVID-19. With no vaccine currently available, the search for effective treatments is a timely approach. The potential impact of such a therapeutic agent, if effective, can be quite vast given that it can be readily used by anyone and, most importantly, is affordable in many countries.

Eligibility criteria: Inclusion Criteria:

* Adults over 40 years of age; and
* Mild to moderate symptoms including fever, dry cough, and tiredness; and
* Tested positive for SARS-Cov-2, via virological diagnosis (PCR), in the last 7 days; and
* Not hospitalized at the time of randomization, with no limitations on activities; and
* Willingness to complete questionnaires and records associated with the study.

Exclusion Criteria:

* Hospitalized patients at the time of enrollment; or
* Known allergy to study medication or its non-medicinal ingredients; or
* Currently taking açai extract or juice; or
* Chronic severe renal impairment (creatinine clearance \<30 mL/min or on renal replacement therapy); or
* Pregnant or breastfeeding patients; or
* Women who are planning to become pregnant during the study; or
* End-stage cancer or patients in whom imminent demise is anticipated and there is no commitment to active ongoing intervention; or
* Unable to provide informed consent; or
* Patients taking antiplatelet/blood-thinning medication; or
* Patients with unstable metabolic disease/chronic diseases/ diseases with any comorbidities and/or any serious medical condition or abnormality of clinical laboratory tests that precludes the patient's safe participation in and completion of the study or puts them in a greater risk of developing severe symptoms (e.g. Individuals with an acute infectious disease, immune-compromised, self-reported confirmation of HIV, other lung diseases such as asthma, emphysema, neurological conditions); or
* Patients who participated in other clinical research studies 30 days prior to screening; or
* Patients who are participating in another clinical trial at the same time.

Primary outcomes:
measure: 7-point ordinal symptom scale
timeFrame: 30 days
Secondary outcomes:
measure: The composite of all-cause mortality and need for mechanical ventilation
timeFrame: 30 days
measure: The composite of all-cause mortality and hospitalization
timeFrame: 30 days
measure: All-cause mortality
timeFrame: 30 days
measure: Need for mechanical ventilation
timeFrame: 30 days
measure: Need for hospitalization
timeFrame: 30 days
Other outcomes:
Locations:
city: Caxias Do Sul
country: Brazil
facility: Instituto de Pesquisas em Saude (IPS)/ Universidade de Caxias do Sul (UCS)
state: RS
city: Sao Paulo
country: Brazil
facility: Instituto Prevent Senior (IPS) - Hospital Sancta Maggiore
state: SP
city: Toronto
country: Canada
facility: Heart Health Institute Research Inc
state: Ontario
Study officials:
affiliation: Peter Munk Cardiac Centre; University Health Network; University of Toronto
name: Michael Farkouh, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pharmacology & Toxicology; University of Toronto
name: Ana Andreazza, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Machado AK, Andreazza AC, da Silva TM, Boligon AA, do Nascimento V, Scola G, Duong A, Cadona FC, Ribeiro EE, da Cruz IB. Neuroprotective Effects of Acai (Euterpe oleracea Mart.) against Rotenone In Vitro Exposure. Oxid Med Cell Longev. 2016;2016:8940850. doi: 10.1155/2016/8940850. Epub 2016 Oct 3.
citation: Machado AK, Cadoná FC, Assmann CE, Andreazza AC, Duarte MMMF, Branco CS, Zhou X, Souza DV, Ribeiro EE, Cruz IBM. Açaí (Euterpe oleracea Mart.) has anti-inflammatory potential through NLRP3-inflammasome modulation. Journal of Functional Foods. Volume 56, 2019, Pages 364-371, https://doi.org/10.1016/j.jff.2019.03.034.
citation: Kim HK, Chen W, Andreazza AC. The Potential Role of the NLRP3 Inflammasome as a Link between Mitochondrial Complex I Dysfunction and Inflammation in Bipolar Disorder. Neural Plast. 2015;2015:408136. doi: 10.1155/2015/408136. Epub 2015 May 13.
citation: Kim HK, Andreazza AC, Elmi N, Chen W, Young LT. Nod-like receptor pyrin containing 3 (NLRP3) in the post-mortem frontal cortex from patients with bipolar disorder: A potential mediator between mitochondria and immune-activation. J Psychiatr Res. 2016 Jan;72:43-50. doi: 10.1016/j.jpsychires.2015.10.015. Epub 2015 Oct 26.
citation: Ulbricht C, Brigham A, Burke D, Costa D, Giese N, Iovin R, Grimes Serrano JM, Tanguay-Colucci S, Weissner W, Windsor R. An evidence-based systematic review of acai (Euterpe oleracea) by the Natural Standard Research Collaboration. J Diet Suppl. 2012 Jun;9(2):128-47. doi: 10.3109/19390211.2012.686347.
citation: Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 May 7;382(19):1787-1799. doi: 10.1056/NEJMoa2001282. Epub 2020 Mar 18.