Randomized Proof-of-Concept Trial to Evaluate the Safety and Explore the Effectiveness of Resveratrol, a Plant Polyphenol, for COVID-19

Randomized Double-Blind Placebo-Controlled Proof-of-Concept Trial of Resveratrol, a Plant Polyphenol, for the Outpatient Treatment of Mild Coronavirus Disease (COVID-19)

Resveratrol is a plant polyphenol (that is sold commercially as a supplement) that might help fight coronavirus as well as help protect the body from the effects of disease (COVID-19) caused by the infection. In this proof-of-concept pilot study we will compare the effects of resveratrol to placebo to assess the safety of the resveratrol and explore effectiveness.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Resveratrol; Dietary supplement: Vitamin D3

Detailed Description

This randomized placebo-controlled trial is for the outpatient treatment of (Coronavirus Disease 2019) COVID-19. The purpose of this trial is to evaluate the safety and explore the effectiveness of resveratrol, a plant polyphenol, being re-purposed for patients with early COVID-19. Published in vitro data supports that this polyphenol inhibits coronavirus replication while separately published in silico (computer molecular docking analysis) reports have identified specific molecular targets of resveratrol against (Severe Acute Respiratory Syndrome - Coronavirus 2) SARS-CoV-2. Animal studies also demonstrate that resveratrol is effective at preventing lung injury and death in certain animal models of viral infections. Furthermore, the products long history as an anti-inflammatory might prevent the cytokine storm that is associated with worse outcomes in COVID-19.

200 subjects, 45 and older, (100 receiving the plant polyphenol, 100 receiving placebo) will be enrolled in study to compare whether taking resveratrol will reduce the rate of hospitalization. Subjects will take capsules 4 times a day for a minimum of 7 days (up to 15 days depending on duration of symptoms) plus both groups will receive Vitamin D3 100,000 IU to augment the effects of resveratrol. Resveratrol will be given as 1gm 4 times per day. Placebo tablets will contain brown rice flour in visually identical capsules. The primary outcome measure for this trial is reduction in hospitalization at 21 days from enrollment.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Mt Carmel HealthSystems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Outpatients who test positive for infection with SARS-CoV-2.
• Age ≥45 years
• Mild COVID-19 based on World Health Organization (WHO) Baseline Severity Categorization
• Symptom duration ≤ 10 days, or <72 hours of new respiratory symptoms.
• Patient must have access to the internet or a smartphone to complete surveys.
• English-speaking patients

Exclusion Criteria:

• Diagnosed or suspected cognitive impairment that would prevent the patient from cooperating with study procedures, as judged by the screening clinician
• Asymptomatic patients (e.g. patients who were screened without symptoms but tested positive)
• Known or suspected liver disease or Hepatitis C
• Known kidney disease with estimate Glomerular Filtration Rate (eGFR) <60
• Patients on warfarin, Novel Oral Anticoagulants (NOACs), HIV Protease Inhibitors, immunosuppressants, hydroxychloroquine/chloroquine, and other medication with a narrow therapeutic window.
• Allergy to grapes or rice.
• Co-morbidities with a high likelihood of hospitalization within 30 days (e.g., current cancer treatment, severe Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF))
• Currently pregnant
• Hospitalization

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
Active Comparator: Resveratrol with Vitamin D3; Resveratrol 1000mg four times per day for 15 days. Vitamin D3 100,000 IU on day 1	Drug: Resveratrol; Resveratrol vs placebo given for 15 days.; Other Names: Placebo; Dietary supplement: Vitamin D3; Vitamin D3 100,000 IU given on day one.
Placebo Comparator: Placebo with Vitamin D3; Placebo capsules 4 times per day for 15 days. Vitamin D3 100,000 IU on day 1	Dietary supplement: Vitamin D3; Vitamin D3 100,000 IU given on day one.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization Rates for COVID-19	Number of study participants admitted to the hospital within 21 days of randomization	21 days from study randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Admission Rates	Number of study participants admitted within 21 who subsequently get admitted to the ICU	21 days from randomization
Invasive Ventilation Rates	Number of study participants who get admitted with 21 day of randomization who receiving invasive ventilation.	21 days from randomization
Pneumonia	Number of study participants are diagnosed with pneumonia with 21 day of randomization	21 days from randomization
Pulmonary Embolism	Number of study participants are diagnosed with pulmonary embolism with 21 day of randomization	21 days from start of randomization.
Death	Number of study participants who died with 21 day of randomization	Within 21 days from randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Diarrhea, nausea, abdominal cramping	60 days from randomization

Collaborators and Investigators

• Sponsor: Marvin McCreary, MD
• Investigators: Principal Investigator: Marvin R McCreary, Mount Carmel Health System

Publications and helpful links

General Publications

• McCreary MR, Schnell PM, Rhoda DA. Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19). Sci Rep. 2022 Jun 29;12(1):10978. doi: 10.1038/s41598-022-13920-9.
• McCreary MR, Schnell PM, Rhoda DA. Randomized Double-blind Placebo-controlled Proof-of-concept Trial of Resveratrol for Outpatient Treatment of Mild Coronavirus Disease (COVID-19). Res Sq. 2021 Sep 13:rs.3.rs-861831. doi: 10.21203/rs.3.rs-861831/v1. Preprint.

Helpful Links

• Recruitment website
• Peer reviewed final publication

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2020
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 22, 2020
• First Posted (Actual): May 26, 2020

Study Record Updates

• Last Update Posted (Actual): February 24, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; COVID; Vitamin D3; Polyphenol; Cholecalciferol; Resveratrol; Supplement; Stilbene; phytoalexin
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antioxidants; Vitamin D; Cholecalciferol; Resveratrol
• Other Study ID Numbers: McCreary2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

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