Vitamin D, Omega-3, and Combination Vitamins B, C and Zinc Supplementation for the Treatment and Prevention of COVID-19

Study Overview
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Brief Summary
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The NUTROVID Factorial Trials The purpose of the NUTROVID-Prevent and NUTROVID-Treat Factorial Trials is to determine whether Vitamin B Complex, Vitamin C, and Zinc; Vitamin D; and Omega3, taken at dosages approximating recommended dosages, can reduce the risk of COVID-19 infection, hospitalization, mortality.

Detailed Description
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Inadequate vitamin intake is common in Mexico. Vitamin deficiency is hypothesized as a risk factor for COVID-19 infection and severe outcomes. Specifically, Vitamin D has been hypothesized as a regulator of the inflammatory cytokine response; Vitamin C may help reduce the risk of a cytokine storm and support the immune system; Vitamin B reduces pro-inflammatory cytokine levels, helps improve respiratory function, reduces hypercoagulability, and promotes endothelial structural integrity; Resolvins, derived from Omega3s, are a type of specialized pro-resolving lipid autacoid mediators hypothesized to prevent cytokine storms. Elemental Zinc is hypothesized to inhibit the replication of viruses. The NUTROVID-Prevent and NUTROVID-Treat Factorial Trials are testing the efficacy of these supplements (Vitamins B, C, D, Zinc, and Omega 3) when used over a 60 day period among those who test positive (Treat) and negative (Prevent) for SARS-COV-2 via a PCR test. The NUTROVID Trials utilize an innovative and cost-efficient approach, leveraging the existing infrastructure of the hospital system in San Luis Potosí province of Mexico. For NUTROVID-Treat, we aim to enroll  1,800 adults who have recently tested positive for SARS-Cov-2 and who have given informed consent. These  1,800 adult females and males age 18 or older will be enrolled and randomized into the NUTROVID Treat Factorial Trial's 2x2x2 arms, in which 50% of the population will have a chance to receive any combination of the 3 supplement formulations; the other 50% will receive the respective placebos. Those who test negative will be randomized into the NUTROVID-Prevent Factorial Trial's 2x2x2 arms, in which 50% of the population will have a chance to receive any combination of the 3 supplement formulations; the other 50% will receive the respective placebos. For NUTROVID-Prevent, we also aim to recruit  1,800 adults, females and males. Hospital staff will review medical records for vital events and conduct patient and family follow-up until  November 2021.

Official Title
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Prevent and Treat Double-Blind Factorial Randomized Trials of Daily Oral Vitamin D, Omega 3, and Combination Vitamins B, C and Zinc Supplementation for the Treatment and Prevention of COVID-19

Conditions
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Covid19

Intervention / Treatment
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* Dietary Supplement: Vitamin D
* Dietary Supplement: Omega DHA / EPA
* Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Positive SARS-CoV-2 Test group (Target enrollment: N=1,800) NUTROVID Treat Trial: Adult men/women recently diagnosed with COVID-19 (positive PCR test for SARS-CoV-2 coronavirus) within <=5 days of symptom onset; and satisfying one of these risk factors: >=50 years old; or Diabetic & >=40 years old; or Obese & >=40 years old. Negative SARS-CoV-2 Test group (Target enrollment: N=1,800) NUTROVID Prevent Trial: Adult men/women recently tested negative for COVID-19 (negative PCR test for SARS-CoV-2 coronavirus); and satisfying one of these risk factors: >=50 years old; or Diabetic & >=40 years old; or Obese & >=40 years old. Signed Informed Consent Form Exclusion Criteria: Patients requiring immediate intubation or deemed likely to die within 48 hours. Patients deemed likely for transfer to an ICU within 48 hours. Patients currently taking oral corticosteroids for any reason at the time of presentation for care. Patients included in any other interventional trial. Uncontrolled bacterial superinfection. Severe chronic kidney disease (stage 4) or requiring dialysis (i.e. eGFR < 30). Pregnant women or women who are breastfeeding. Immunocompromised patients. Any patient with recent treatment (past 30 days) of immunosuppressive agents including (but not restricted to) DMARDs, corticosteroids, antibody therapy, intravenous immunoglobulins etc. Patients with acute myocardial infarction.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Double-blind randomized, placebo-controlled double blinded 2x2x2 factorial trials (includes 2 trials: treatment cohort and prevention cohort) of the following oral supplementation treatments for up to 60 days per person: Factorial 1 (F1): 4000 IU Vitamin D vs placebo Factorial 2 (F2): 1000mg Omega DHA/EPA vs. placebo Factorial 3 (F3): Combination 1000 mg Vitamin C, Vitamin B complex** and Zinc Acetate, 100 mg/day vs. placebo **(Vitamin B complex components: B12=1 mg; B6=50 mg; B9=2.5 mg; B1
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 - Vitamin D, Omega 3, Vitamins B, C, Zinc<br>Vitamin D of F1 Omega 3 of F2 Vitamins B, C, Zinc of F3 [60 days] | Dietary Supplement: Vitamin D<br>* Daily 4000 IU Vitamin D for 60 days<br>Dietary Supplement: Omega DHA / EPA<br>* Daily 1000mg Omega DHA/EPA for 60 days<br>Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate<br>* Combination 1000 mg Vitamin C, Vitamin B complex** and Zinc Acetate, 100 mg/day for 60 days **(Vitamin B complex components: B12=1 mg; B6=50 mg; B9=2.5 mg; B1=100 mg; B2=100 mg; B3=14 mg; B7=50 mg)<br>|
| Active Comparator: 2 - Vitamin D, Omega 3<br>Vitamin D of F1 Omega 3 of F2 Placebo of F3 [60 days] | Dietary Supplement: Vitamin D<br>* Daily 4000 IU Vitamin D for 60 days<br>Dietary Supplement: Omega DHA / EPA<br>* Daily 1000mg Omega DHA/EPA for 60 days<br>|
| Active Comparator: 3 - Vitamin D, Vitamins B, C, Zinc<br>Vitamin D of F1 Placebo of F2 Vitamins B, C, Zinc of F3 [60 days] | Dietary Supplement: Vitamin D<br>* Daily 4000 IU Vitamin D for 60 days<br>Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate<br>* Combination 1000 mg Vitamin C, Vitamin B complex** and Zinc Acetate, 100 mg/day for 60 days **(Vitamin B complex components: B12=1 mg; B6=50 mg; B9=2.5 mg; B1=100 mg; B2=100 mg; B3=14 mg; B7=50 mg)<br>|
| Active Comparator: 4 - Vitamin D<br>Vitamin D of F1 Placebo of F2 Placebo of F3 [60 days] | Dietary Supplement: Vitamin D<br>* Daily 4000 IU Vitamin D for 60 days<br>|
| Active Comparator: 5 - Omega 3, Vitamins B, C, Zinc,<br>Placebo of F1 Omega 3 of F2 Vitamins B, C, Zinc of F3 [60 days] | Dietary Supplement: Omega DHA / EPA<br>* Daily 1000mg Omega DHA/EPA for 60 days<br>Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate<br>* Combination 1000 mg Vitamin C, Vitamin B complex** and Zinc Acetate, 100 mg/day for 60 days **(Vitamin B complex components: B12=1 mg; B6=50 mg; B9=2.5 mg; B1=100 mg; B2=100 mg; B3=14 mg; B7=50 mg)<br>|
| Active Comparator: 6 - Omega 3<br>Placebo of F1 Omega 3 of F2 Placebo of F3 [60 days] | Dietary Supplement: Omega DHA / EPA<br>* Daily 1000mg Omega DHA/EPA for 60 days<br>|
| Active Comparator: 7 - Vitamins B, C, Zinc<br>Placebo of F1 Placebo of F2 Vitamins B, C, Zinc of F3 [60 days] | Dietary Supplement: Vitamin C, Vitamin B complex and Zinc Acetate<br>* Combination 1000 mg Vitamin C, Vitamin B complex** and Zinc Acetate, 100 mg/day for 60 days **(Vitamin B complex components: B12=1 mg; B6=50 mg; B9=2.5 mg; B1=100 mg; B2=100 mg; B3=14 mg; B7=50 mg)<br>|
| Placebo Comparator: 8 - No Interventions<br>Placebo of F1 Placebo of F2 Placebo of F3 [60 days] | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Covid infection rate (PREVENT Trial only) | 1.a. Incidence of positive PCR at  1 month and  2 months; 1.b. Incidence of symptomatic positive PCR and asymptomatic positive PCR at 1 month and 2 months. | 30 and 60 days | 
| Incidence of severe outcome (TREAT Trial only) | 1.a. Incidence of severe outcome (mortality or ICU admission or intubation) up to 30 days. 1.b. Incidence of severe outcome (mortality or ICU admission or intubation) from 30-60 days. 1.c. Incidence of severe outcome (mortality or ICU admission or intubation), from 30 days to   November 2021. 1.d. Incidence of severe outcome (mortality or ICU admission or intubation), from 60 days to   November 2021. | 1.a. 1-30 days; 1.b. 30-60; 1.c. 30 days to  November 2021; 1.d. 60 days to   November 2021 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of hospitalization and death (PREVENT Trial only) | 2.a. Incidence of hospitalization, follow-up to   November 2021. 2.b. Incidence of severe outcome (mortality or ICU admission or intubation), follow-up to  November 2021. 2.c. Incidence of death, follow-up to  November 2021. | 1-10 months | 
| Length of hospitalization and death after discharge (TREAT Trial only) | 2.a. Length of hospitalization for admissions less than 30 days from baseline versus for admissions after 30 days from baseline. 2.b. [If available] Incidence of hospital readmission after discharge, follow-up to  November 2021. 2.c. Incidence of death after discharge, follow-up to  November 2021. | 2.a. 1-30 days; 2.b. 1 day(s) to  November 2021, 2.c. 30 days to  November 2021 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Nutritional supplements, Vitamin B, Vitamin C, Elemental Zinc, Cytokine storm, Vitamin D, Vitamin B Complex, Omega 3