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

• ClinicalTrials.gov Identifier: NCT04400890
• Recruitment Status: Active, not recruiting
• First Posted: May 26, 2020
• Last Update Posted: March 9, 2021
• Sponsor: Marvin McCreary, MD
• Information provided by (Responsible Party): Marvin McCreary, MD, Mount Carmel Health System

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Resveratrol; Dietary Supplement: Vitamin D3	Phase 2

Detailed Description:

This randomized placebo-controlled trial is for the outpatient treatment of 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 SARS-CoV2. 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Double-Blind Placebo-Controlled Proof-of-Concept Trial of Resveratrol, a Plant Polyphenol, for the Outpatient Treatment of Mild Coronavirus Disease (COVID-19)
• Actual Study Start Date: September 12, 2020
• Actual Primary Completion Date: January 11, 2021
• Estimated Study Completion Date: March 2021

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Hospitalization rates for COVID-19 [ Time Frame: 21 days from study randomization ]
   Proportion of study participants admitted to the hospital within 21 days of randomization

Secondary Outcome Measures :

1. ICU Admission Rates [ Time Frame: 21 days from randomization ]
   Proportion of study participants admitted within 21 who subsequently get admitted to the ICU
2. Invasive Ventilation Rates [ Time Frame: 21 days from randomization ]
   Proportion of study participants who get admitted with 21 day of randomization who receiving invasive ventilation.
3. Pneumonia [ Time Frame: 21 days from randomization ]
   Proportion of study participants are diagnosed with pneumonia with 21 day of randomization

Other Outcome Measures:

1. Adverse events [ Time Frame: 60 days from randomization ]
   Diarrhea, nausea, abdominal cramping

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Outpatients who test positive for infection with SARS-CoV-2.
• Age ≥45 years
• Mild COVID-19 based on 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 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 COPD or CHF)
• Currently pregnant
• Hospitalization

Contacts and Locations

Locations

United States, Ohio

Mt Carmel HealthSystems

Columbus, Ohio, United States, 43213

Sponsors and Collaborators

Marvin McCreary, MD

Investigators

• Principal Investigator: Marvin R McCreary; Mount Carmel Health System

More Information

Additional Information:

Recruitment website 

• Responsible Party: Marvin McCreary, MD, Emergency Physician, Mount Carmel Health System
• ClinicalTrials.gov Identifier: NCT04400890
• Other Study ID Numbers: McCreary2020
• First Posted: May 26, 2020
• Last Update Posted: March 9, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Clinical Study Report (CSR)

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Marvin McCreary, MD, Mount Carmel Health System:

Coronavirus; SARS-CoV-2; COVID; Vitamin D3; Cholecalciferol; Supplement; Polyphenol; Resveratrol; Stilbene; phytoalexin

Additional relevant MeSH terms:

Vitamin D; Cholecalciferol; Resveratrol; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antimutagenic Agents; Anticarcinogenic Agents