Clinical trial NCT04828538: Vitamin D, Omega-3, and Combination Vitamins B, C and Zinc Supplementation for the Treatment and Prevention of COVID-19
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Covid19
Keywords: Covid19
Nutritional supplements
Vitamin B
Vitamin C
Elemental Zinc
Cytokine storm
Vitamin D
Vitamin B Complex
Omega 3
Lead sponsor: Hospital de la Soledad
Sponsor class: OTHER_GOV
First posted: 2021-04-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention 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
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Covid infection rate (PREVENT Trial only)
timeFrame: 30 and 60 days
measure: Incidence of severe outcome (TREAT Trial only)
timeFrame: 1.a. 1-30 days; 1.b. 30-60; 1.c. 30 days to ~November 2021; 1.d. 60 days to ~ November 2021
Secondary outcomes:
measure: Incidence of hospitalization and death (PREVENT Trial only)
timeFrame: 1-10 months
measure: Length of hospitalization and death after discharge (TREAT Trial only)
timeFrame: 2.a. 1-30 days; 2.b. 1 day(s) to ~November 2021, 2.c. 30 days to ~November 2021
Other outcomes:
measure: Changes in HbA1c (PREVENT Trial only)
timeFrame: 1-30; 1-60 days
measure: Change in diabetes status (PREVENT Trial only)
timeFrame: 1-30; 1-60 days
measure: Change in weight (PREVENT Trial only)
timeFrame: 1-30; 1-60 days
measure: Incidence of COVID -19 symptoms at 1 month and 2 months (PREVENT Trial only)
timeFrame: 1-30; 1-60 days
measure: Incidence of hospital readmission (PREVENT Trial only)
timeFrame: 1-30; 1-60 days; 1 day to ~November 2021
measure: Incidence of ICU admission (PREVENT Trial only)
timeFrame: 1-30; 1-60 days; 1 day to ~November 2021
measure: Incidence of intubation (PREVENT Trial only)
timeFrame: 1-30; 1-60 days; 1 day to ~November 2021
measure: Incidence of Vaccination (PREVENT Trial only)
timeFrame: 1-30; 1-60 days; 1 day to ~November 2021
measure: Change in HbA1c at 1 month and 2 months (TREAT Trial only)
timeFrame: 1-30 days and 1-60 days
measure: Change in diabetes status at 1 month and 2 months (TREAT Trial only)
timeFrame: 1-30 days and 1-60 days
measure: Change in weight at 1 month and 2 months (TREAT Trial only)
timeFrame: 1-30 days and 1-60 days
measure: Incidence of COVID -19 symptoms at 1 month and 2 months (TREAT Trial only)
timeFrame: 1-30 days and 1-60 days
measure: Incidence of depression (TREAT Trial only)
timeFrame: ~1-60 days
measure: Incidence of vaccination (TREAT Trial only)
timeFrame: 1-30; 1-60 days; 1 day to ~November 2021
measure: Incidence of vaccine hesitancy (TREAT Trial only)
timeFrame: ~1-60 days
measure: ICU readmission (TREAT Trial only)
timeFrame: 1-30; 1-60 days; 1 day to ~November 2021
measure: Incidence of Intubation (upon readmission) (TREAT Trial only)
timeFrame: 1-30; 1-60 days; 1 day to ~November 2021
Locations:
city: San Luis Potosí
country: Mexico
facility: Hospital de Soledad
state: SLP
Study officials:
affiliation: General Hospital Soledad
name: José Yañez
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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. No abstract available.
citation: 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.
citation: Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev. 2013 Jun 18;(6):CD001364. doi: 10.1002/14651858.CD001364.pub4.