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

Tracking Information

• First Submitted Date: May 22, 2020
• First Posted Date: May 26, 2020
• Last Update Posted Date: March 9, 2021
• Actual Study Start Date: September 12, 2020
• Actual Primary Completion Date: January 11, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 31, 2020)

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

Original Primary Outcome Measures (submitted: May 22, 2020)

Hospitalization rates for COVID-19 [ Time Frame: 21 days from testing positive from COVID-19 ]

Proportion of study participants admitted to the hospital within 21 days of testing positive

Current Secondary Outcome Measures (submitted: March 4, 2021)

• ICU Admission Rates [ Time Frame: 21 days from randomization ]
  Proportion of study participants admitted within 21 who subsequently get admitted to the ICU
• 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.
• Pneumonia [ Time Frame: 21 days from randomization ]
  Proportion of study participants are diagnosed with pneumonia with 21 day of randomization

Original Secondary Outcome Measures (submitted: May 22, 2020)

• ICU Admission Rates [ Time Frame: 21 days from testing positive from COVID-19 ]
  Proportion of study participants admitted to the ICU within 21 days of testing positive
• Invasive Ventilation Rates [ Time Frame: 21 days from testing positive from COVID-19 ]
  Proportion of study participants receiving invasive ventilation within 21 days of testing positive

Current Other Pre-specified Outcome Measures (submitted: September 12, 2020)

Adverse events [ Time Frame: 60 days from randomization ]

Diarrhea, nausea, abdominal cramping

Original Other Pre-specified Outcome Measures (submitted: May 22, 2020)

• Reported symptom severity [ Time Frame: 21 days from testing positive from COVID-19 ]
  Modified BORG scale, visual analog scale for fatigue
• Adverse events [ Time Frame: 21 days from testing positive from COVID-19 ]
  Diarrhea, nausea, abdominal cramping

Descriptive Information

• Brief Title: Randomized Proof-of-Concept Trial to Evaluate the Safety and Explore the Effectiveness of Resveratrol, a Plant Polyphenol, for COVID-19
• 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)
• 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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: COVID-19

Intervention

• 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.

Study Arms

• Active Comparator: Resveratrol with Vitamin D3
  Resveratrol 1000mg four times per day for 15 days. Vitamin D3 100,000 IU on day 1
  Interventions:

  • Drug: Resveratrol
  • Dietary Supplement: Vitamin D3
• Placebo Comparator: Placebo with Vitamin D3
  Placebo capsules 4 times per day for 15 days. Vitamin D3 100,000 IU on day 1
  Intervention: Dietary Supplement: Vitamin D3

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 4, 2021): 100
• Original Estimated Enrollment (submitted: May 22, 2020): 200
• Estimated Study Completion Date: March 2021
• Actual Primary Completion Date: January 11, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04400890
• Other Study ID Numbers: McCreary2020
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

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

• Responsible Party: Marvin McCreary, MD, Mount Carmel Health System
• Study Sponsor: Marvin McCreary, MD
• Collaborators: Not Provided

Investigators

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

• PRS Account: Mount Carmel Health System
• Verification Date: March 2021