COVID-19
Conditions
Keywords
Coronavirus, SARS-CoV-2, COVID, Vitamin D3, Cholecalciferol, Supplement, Polyphenol, Resveratrol, Stilbene, phytoalexin
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.
Interventions
DRUGResveratrol
Resveratrol vs placebo given for 15 days.
DIETARY_SUPPLEMENTVitamin D3
Vitamin D3 100,000 IU given on day one.
Sponsors
Marvin McCreary, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization Rates for COVID-19 | 21 days from study randomization | Number of study participants admitted to the hospital within 21 days of randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Admission Rates | 21 days from randomization | Number of study participants admitted within 21 who subsequently get admitted to the ICU |
| Invasive Ventilation Rates | 21 days from randomization | Number of study participants who get admitted with 21 day of randomization who receiving invasive ventilation. |
| Pulmonary Embolism | 21 days from start of randomization. | Number of study participants are diagnosed with pulmonary embolism with 21 day of randomization |
| Death | Within 21 days from randomization | Number of study participants who died with 21 day of randomization |
| Pneumonia | 21 days from randomization | Number of study participants are diagnosed with pneumonia with 21 day of randomization |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 60 days from randomization | Diarrhea, nausea, abdominal cramping |
Countries
United States
Participant flow
Recruitment details
Between September 13, 2020 and December 11, 2020, 1,694 patients were telephoned within 24-h of testing positive for COVID-19 to be recruited into the clinical trial . One-hundred-five were enrolled and randomized. Five withdrew after receiving treatment packets (four withdrew before starting treatment and one withdrew after one treatment day citing too many pills as reason for withdrawal).
Pre-assignment details
One-hundred-five subjects were enrolled and randomized. Four participants withdrew before starting treatment. One participant withdrew after one treatment day citing too many pills as reason for withdrawal.
Participants by arm
| Arm | Count |
|---|---|
| Resveratrol With Vitamin D3 Resveratrol 1000mg four times per day for up to 15 days (7 days minimum). Vitamin D3 100,000 IU on day 1
Vitamin D3: Vitamin D3 100,000 IU given on day one. | 53 |
| Placebo With Vitamin D3 Placebo capsules 4 times per day for up to 15 days (7 days minimum). Vitamin D3 100,000 IU on day 1
Vitamin D3: Vitamin D3 100,000 IU given on day one. | 52 |
| Total | 105 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Total | Resveratrol With Vitamin D3 | Placebo With Vitamin D3 |
|---|---|---|---|
| Age, Continuous | 56.0 years STANDARD_DEVIATION 8.98 | 55.7 years STANDARD_DEVIATION 8.55 | 56.3 years STANDARD_DEVIATION 9.46 |
| Angiotensin Converting Enzyme Inhibitor (ACEI) / Angiotensin Receptor Blocker (ARB) use | 15 Participants | 5 Participants | 10 Participants |
| BMI | 30.2 kg/m^2 STANDARD_DEVIATION 6.2 | 29.1 kg/m^2 STANDARD_DEVIATION 4.68 | 31.4 kg/m^2 STANDARD_DEVIATION 7.32 |
| Cardiovascular Disease | 6 Participants | 3 Participants | 3 Participants |
| Chronic Lung Disease | 19 Participants | 10 Participants | 9 Participants |
| Current Smoker | 3 Participants | 1 Participants | 2 Participants |
| Diabetes Mellitus | 10 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 43 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 15 Participants | 9 Participants | 6 Participants |
| Former Smoker | 20 Participants | 8 Participants | 12 Participants |
| High Risk Comorbidity= NO | 73 Participants | 38 Participants | 35 Participants |
| High Risk Comorbidity= YES | 32 Participants | 15 Participants | 17 Participants |
| Immunocompromised | 0 Participants | 0 Participants | 0 Participants |
| Inhaled Steroid Use | 4 Participants | 0 Participants | 4 Participants |
| Liver Disease | 0 Participants | 0 Participants | 0 Participants |
| Oral Steroid Use | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 93 Participants | 47 Participants | 46 Participants |
| Renal Disease | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 62 Participants | 29 Participants | 33 Participants |
| Sex: Female, Male Male | 43 Participants | 24 Participants | 19 Participants |
| Vitamin D use | 8 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 50 / 50 | 50 / 50 |
| serious Total, serious adverse events | 4 / 50 | 8 / 50 |
Outcome results
Primary
Hospitalization Rates for COVID-19
Number of study participants admitted to the hospital within 21 days of randomization
Time frame: 21 days from study randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Resveratrol With Vitamin D3 | Hospitalization Rates for COVID-19 | 1 Participants |
| Placebo With Vitamin D3 | Hospitalization Rates for COVID-19 | 3 Participants |
Secondary
Death
Number of study participants who died with 21 day of randomization
Time frame: Within 21 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Resveratrol With Vitamin D3 | Death | 0 Participants |
| Placebo With Vitamin D3 | Death | 0 Participants |
Secondary
ICU Admission Rates
Number of study participants admitted within 21 who subsequently get admitted to the ICU
Time frame: 21 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Resveratrol With Vitamin D3 | ICU Admission Rates | 0 Participants |
| Placebo With Vitamin D3 | ICU Admission Rates | 0 Participants |
Secondary
Invasive Ventilation Rates
Number of study participants who get admitted with 21 day of randomization who receiving invasive ventilation.
Time frame: 21 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Resveratrol With Vitamin D3 | Invasive Ventilation Rates | 0 Participants |
| Placebo With Vitamin D3 | Invasive Ventilation Rates | 0 Participants |
Secondary
Pneumonia
Number of study participants are diagnosed with pneumonia with 21 day of randomization
Time frame: 21 days from randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Resveratrol With Vitamin D3 | Pneumonia | 4 Participants |
| Placebo With Vitamin D3 | Pneumonia | 8 Participants |
Secondary
Pulmonary Embolism
Number of study participants are diagnosed with pulmonary embolism with 21 day of randomization
Time frame: 21 days from start of randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Resveratrol With Vitamin D3 | Pulmonary Embolism | 1 Participants |
| Placebo With Vitamin D3 | Pulmonary Embolism | 1 Participants |
Other Pre-specified
Adverse Events
Diarrhea, nausea, abdominal cramping
Time frame: 60 days from randomization