The Açaí Berry COVID-19 Anti-Inflammation Trial (ACAI)

Randomized Clinical Trial of Açaí Palm Berry Extract as an Intervention in Patients Diagnosed With COVID-19

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.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID
• Intervention / Treatment: Dietary supplement: Açaí palm berry extract - natural product; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 480
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Caxias Do Sul, RS, Brazil
      • Instituto de Pesquisas em Saude (IPS)/ Universidade de Caxias do Sul (UCS)
  • SP
    • Sao Paulo, SP, Brazil
      • Instituto Prevent Senior (IPS) - Hospital Sancta Maggiore
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M1B 4Z8
      • Heart Health Institute Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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: Açaí palm berry extract; Açaí palm berry extract is a powerful antioxidant with no known side-effects and is widely consumed in Brazil. Açaí palm berry chemical composition has been established and includes several antioxidants - gallic acid, catechin, chlorogenic acid, caffeic acid, p-coumaric acid, epicatechin, orientin, cyanidin-3-0-glucoside, luteolin and apigenin. Orientin is the most concentrated compound (7,96mg/g) and this compound is able to modulate the NLRP3 inflammasome.	Dietary supplement: Açaí palm berry extract - natural product; Patients will be prescribed to take 1 capsule (520mg) of Açaí Palm Berry every 8 hours for a total of 3 capsules a day, during 30 days. Total dose: 1,560mg/day of Açaí Berry extract.
Placebo Comparator: Placebo arm; This study will be double-blinded and placebo-controlled. To ensure double-blinding, placebo and active compound capsules will be over-encapsulated with DBCAPS® capsules, which were developed with a tamper-evident design to address the clinical trial challenges of testing without bias. These capsules are made of gelatin and have no interaction with bioavailability.	Other: Placebo; Patients will take 1 placebo pill every 8 hours (total of 3 capsules a day) for 30 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7-point ordinal symptom scale	Symptom comparison between patients from the treatment vs control group, using an ordinal symptom scale based on the WHO scale. Patients who were hospitalized will be classified according to their worst score over 30 days and non-hospitalized patients according to their score at 30 days.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The composite of all-cause mortality and need for mechanical ventilation	First occurrence of all-cause mortality or need for mechanical ventilation	30 days
The composite of all-cause mortality and hospitalization	First occurrence of all-cause mortality or hospitalization	30 days
All-cause mortality	All-cause mortality	30 days
Need for mechanical ventilation	Need for mechanical ventilation	30 days
Need for hospitalization	Need for hospitalization	30 days

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: University of Toronto
• Investigators: Principal Investigator: Michael Farkouh, MD, MSc, Peter Munk Cardiac Centre; University Health Network; University of Toronto; Principal Investigator: Ana Andreazza, PhD, Department of Pharmacology & Toxicology; University of Toronto

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Anticipated): June 15, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: May 24, 2020
• First Submitted That Met QC Criteria: May 24, 2020
• First Posted (Actual): May 27, 2020

Study Record Updates

• Last Update Posted (Actual): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 27, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: COVID; açaí berry; community care patients
• Other Study ID Numbers: CTO3176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No