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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Resveratrol
* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Resveratrol with Vitamin D3<br>Resveratrol 1000mg four times per day for 15 days. Vitamin D3 100,000 IU on day 1 | Drug: Resveratrol<br>* Resveratrol vs placebo given for 15 days.<br>* Other names: Placebo;Dietary Supplement: Vitamin D3<br>* Vitamin D3 100,000 IU given on day one.<br>|
| Placebo Comparator: Placebo with Vitamin D3<br>Placebo capsules 4 times per day for 15 days. Vitamin D3 100,000 IU on day 1 | Dietary Supplement: Vitamin D3<br>* Vitamin D3 100,000 IU given on day one.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stilbene, Coronavirus, SARS-CoV-2, COVID, Vitamin D3, Cholecalciferol, Supplement, Polyphenol, Resveratrol, phytoalexin