Clinical trial NCT04400890: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: Coronavirus
SARS-CoV-2
COVID
Vitamin D3
Cholecalciferol
Supplement
Polyphenol
Resveratrol
Stilbene
phytoalexin
Lead sponsor: Mount Carmel Health System
Sponsor class: OTHER
First posted: 2020-05-26
Enrollment: 105
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 (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.

Eligibility criteria: 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

Primary outcomes:
measure: Hospitalization Rates for COVID-19
timeFrame: 21 days from study randomization
Secondary outcomes:
measure: ICU Admission Rates
timeFrame: 21 days from randomization
measure: Invasive Ventilation Rates
timeFrame: 21 days from randomization
measure: Pneumonia
timeFrame: 21 days from randomization
measure: Pulmonary Embolism
timeFrame: 21 days from start of randomization.
measure: Death
timeFrame: Within 21 days from randomization
Other outcomes:
measure: Adverse Events
timeFrame: 60 days from randomization
Locations:
city: Columbus
country: United States
facility: Mt Carmel HealthSystems
state: Ohio
Study officials:
affiliation: Mount Carmel Health System
name: Marvin R McCreary
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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 [Preprint]. 2021 Sep 13:rs.3.rs-861831. doi: 10.21203/rs.3.rs-861831/v1.