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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Covid19
• Intervention / Treatment: Other: Placebo; Dietary supplement: Vitamin D; Dietary supplement: Omega DHA / EPA; Dietary supplement: Vitamin C, Vitamin B complex and Zinc Acetate

Detailed Description

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.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • SLP
    • San Luis Potosí, SLP, Mexico, 78435
      • Hospital de Soledad

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1 - Vitamin D, Omega 3, Vitamins B, C, Zinc; Vitamin D of F1 Omega 3 of F2 Vitamins B, C, Zinc of F3 [60 days]	Dietary supplement: Vitamin D; Daily 4000 IU Vitamin D for 60 days; Dietary supplement: Omega DHA / EPA; Daily 1000mg Omega DHA/EPA for 60 days; Dietary supplement: Vitamin C, Vitamin B complex and Zinc Acetate; 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)
Active Comparator: 2 - Vitamin D, Omega 3; Vitamin D of F1 Omega 3 of F2 Placebo of F3 [60 days]	Dietary supplement: Vitamin D; Daily 4000 IU Vitamin D for 60 days; Dietary supplement: Omega DHA / EPA; Daily 1000mg Omega DHA/EPA for 60 days
Active Comparator: 3 - Vitamin D, Vitamins B, C, Zinc; Vitamin D of F1 Placebo of F2 Vitamins B, C, Zinc of F3 [60 days]	Dietary supplement: Vitamin D; Daily 4000 IU Vitamin D for 60 days; Dietary supplement: Vitamin C, Vitamin B complex and Zinc Acetate; 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)
Active Comparator: 4 - Vitamin D; Vitamin D of F1 Placebo of F2 Placebo of F3 [60 days]	Dietary supplement: Vitamin D; Daily 4000 IU Vitamin D for 60 days
Active Comparator: 5 - Omega 3, Vitamins B, C, Zinc,; Placebo of F1 Omega 3 of F2 Vitamins B, C, Zinc of F3 [60 days]	Dietary supplement: Omega DHA / EPA; Daily 1000mg Omega DHA/EPA for 60 days; Dietary supplement: Vitamin C, Vitamin B complex and Zinc Acetate; 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)
Active Comparator: 6 - Omega 3; Placebo of F1 Omega 3 of F2 Placebo of F3 [60 days]	Dietary supplement: Omega DHA / EPA; Daily 1000mg Omega DHA/EPA for 60 days
Active Comparator: 7 - Vitamins B, C, Zinc; Placebo of F1 Placebo of F2 Vitamins B, C, Zinc of F3 [60 days]	Dietary supplement: Vitamin C, Vitamin B complex and Zinc Acetate; 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)
Placebo Comparator: 8 - No Interventions; Placebo of F1 Placebo of F2 Placebo of F3 [60 days]	Other: Placebo; Placebo

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in HbA1c (PREVENT Trial only)	Change in HbA1c at 1 month and 2 months	1-30; 1-60 days
Change in diabetes status (PREVENT Trial only)	Change in diabetes status at 1 month and 2 months	1-30; 1-60 days
Change in weight (PREVENT Trial only)	Change in weight at 1 month and 2 months	1-30; 1-60 days
Incidence of COVID -19 symptoms at 1 month and 2 months (PREVENT Trial only)	[If available] Incidence of COVID -19 symptoms at 1 month and 2 months	1-30; 1-60 days
Incidence of hospital readmission (PREVENT Trial only)	[If available] Incidence of COVID -19 symptoms at 1 month and 2 months with follow-up to ~November 2021	1-30; 1-60 days; 1 day to ~November 2021
Incidence of ICU admission (PREVENT Trial only)	[If available] Incidence of ICU admission (PREVENT Trial only)	1-30; 1-60 days; 1 day to ~November 2021
Incidence of intubation (PREVENT Trial only)	[If available] Incidence of intubation (PREVENT Trial only)	1-30; 1-60 days; 1 day to ~November 2021
Incidence of Vaccination (PREVENT Trial only)	[If available] Incidence of vaccination	1-30; 1-60 days; 1 day to ~November 2021
Change in HbA1c at 1 month and 2 months (TREAT Trial only)	[If available] Change in HbA1c at 1 month and 2 months.	1-30 days and 1-60 days
Change in diabetes status at 1 month and 2 months (TREAT Trial only)	[If available] Change in diabetes status at 1 month and 2 months.	1-30 days and 1-60 days
Change in weight at 1 month and 2 months (TREAT Trial only)	[If available] Change in weight at 1 month and 2 months	1-30 days and 1-60 days
Incidence of COVID -19 symptoms at 1 month and 2 months (TREAT Trial only)	[If available] Incidence of COVID -19 symptoms at 1 month and 2 months.	1-30 days and 1-60 days
Incidence of depression (TREAT Trial only)	[If available] Incidence of depression	~1-60 days
Incidence of vaccination (TREAT Trial only)	[If available] Incidence of vaccination	1-30; 1-60 days; 1 day to ~November 2021
Incidence of vaccine hesitancy (TREAT Trial only)	[If available] Incidence of vaccine hesitancy	~1-60 days
ICU readmission (TREAT Trial only)	[If available] ICU readmission	1-30; 1-60 days; 1 day to ~November 2021
Incidence of Intubation (upon readmission) (TREAT Trial only)	[If available] Incidence of Intubation	1-30; 1-60 days; 1 day to ~November 2021

Collaborators and Investigators

• Sponsor: Hospital de la Soledad
• Investigators: Principal Investigator: José Yañez, General Hospital Soledad

Publications and helpful links

General Publications

• Laird E, Rhodes J, Kenny RA. Vitamin D and Inflammation: Potential Implications for Severity of Covid-19. Ir Med J. 2020 May 7;113(5):81.
• Boretti A, Banik BK. Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome. PharmaNutrition. 2020 Jun;12:100190. doi: 10.1016/j.phanu.2020.100190. Epub 2020 Apr 21. Review.
• Panigrahy D, Gilligan MM, Huang S, Gartung A, Cortes-Puch I, Sime PJ, Phipps RP, Serhan CN, Hammock BD. Inflammation resolution: a dual-pronged approach to averting cytokine storms in COVID-19? Cancer Metastasis Rev. 2020 Jun;39(2):337-340. doi: 10.1007/s10555-020-09889-4.
• Shakoor H, Feehan J, Mikkelsen K, Al Dhaheri AS, Ali HI, Platat C, Ismail LC, Stojanovska L, Apostolopoulos V. Be well: A potential role for vitamin B in COVID-19. Maturitas. 2021 Feb;144:108-111. doi: 10.1016/j.maturitas.2020.08.007. Epub 2020 Aug 15.
• Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, Alcala Diaz JF, Lopez Miranda J, Bouillon R, Quesada Gomez JM. "Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study". J Steroid Biochem Mol Biol. 2020 Oct;203:105751. doi: 10.1016/j.jsbmb.2020.105751. Epub 2020 Aug 29.
• Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013 Jun 18;(6):CD001364. doi: 10.1002/14651858.CD001364.pub4.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: March 12, 2021
• First Submitted That Met QC Criteria: March 31, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Covid19; Vitamin D; Vitamin B; Omega 3; Vitamin C; Nutritional supplements; Elemental Zinc; Cytokine storm; Vitamin B Complex
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Bone Density Conservation Agents; Antioxidants; Hematinics; Vitamin D; Vitamins; Folic Acid; Vitamin B Complex; Ascorbic Acid
• Other Study ID Numbers: 102020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No