Effectiveness and Safety of Two Vitamin D3 Supplementation Regimens in Adults with Early-stage COVID-19

NCT06585995 | Completed DMC

• 1 other identifier: No. 2022/C-015
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

This study aimed to determine the effectiveness and safety of individualized vitamin D3 supplementation in adult patients with early-stage severe COVID-19. The goal was to see if vitamin D3 could reduce the risk of progressing to critical COVID-19, characterized by severe respiratory distress and other life-threatening complications. The research question was: What is the effect of vitamin D3 on serum calcidiol levels during the active phase of the disease in adult patients with COVID-19? The study hypothesized that an accelerated vitamin D3 supplementation regimen in adult patients with COVID-19 would achieve the ideal serum calcidiol level (40-60 ng/ml) during the active phase of the disease. This was a randomized controlled clinical trial with two parallel groups. The first group, the accelerated supplementation group, received a single monthly dose of vitamin D3, while the second group, the daily supplementation group, received a daily dose of vitamin D3 during their hospital stay. A total of 216 patients were included in the study and were randomly assigned to one of the two groups. Key procedures and measurements included the collection of three blood samples from each patient during their hospital stay-at admission (day 1), on day 7, and on day 14. Biomarker analysis measured serum levels of vitamin D3, Von Willebrand Factor, interleukin-6 (IL-6), and glutathione peroxidase. Clinical monitoring was conducted to track the development of critical COVID-19, the need for mechanical ventilation, and overall clinical outcomes, such as recovery or death. The importance of this study lay in the role of vitamin D3 in immune regulation, as it had been identified as a protective factor against severe respiratory infections. By determining the optimal supplementation strategy, this study hoped to improve clinical outcomes for COVID-19 patients, reduce mortality rates, and prevent the progression to critical illness. Inclusion criteria for the study were adult patients aged 18-65 years with early-stage severe COVID-19, who had signed informed consent and had no contraindications for vitamin D3 supplementation. Exclusion criteria included patients with other severe comorbidities, those who were pregnant, those requiring immediate intensive care, and patients with a history of conditions that affect vitamin D metabolism. Safety and efficacy monitoring tracked the vitamin D3 levels and correlated them with inflammation markers, oxidative stress, and thrombotic status to evaluate the impact of supplementation. Clinical progression was also monitored to assess the safety and efficacy of the vitamin D3 regimens. Outcome measures included changes in serum calcidiol levels, correlation of calcidiol levels with biomarkers (IL-6, glutathione peroxidase, Von Willebrand Factor), duration and intensity of COVID-19 symptoms, incidence of critical COVID-19, need for mechanical ventilation, and overall clinical outcomes (recovery or death). This study aimed to provide valuable insights into the role of vitamin D3 in managing severe COVID-19, potentially informing treatment guidelines and improving patient outcomes.

Conditions

COVID-19

Keywords

COVID-19; Cholecalciferol; Vitamin D; Interleukin-6; Glutathione peroxidase; Cough; dyspnea; fatigue; anxiety; depression

Outcome Measures

Primary Outcomes (3)

• Glutathione Peroxidase (GPx) Activity

  This measure evaluates the amount of glutathione peroxidase, such determination is performed by determining the glutathione peroxidase enzyme activity in the plasma of each patient, this parameter is determined with a special glutathione peroxidase enzyme activity determination kit, which indicates the bodys ability to reduce systemic oxidative stress. An increase in GPx activity is expected as a result of vitamin D supplementation.

  Baseline before supplementation, seven days and fourteen days after supplementation

• Serum 25-Hydroxyvitamin D Levels

  Vitamin D (calcidiol ) will be measured in each sample taken from each of the patients, this measurement will be performed by the clinical laboratory of the hospital center. This measurement will confirm the efficacy of the vitamin D supplementation regimen in achieving and maintaining sufficient serum vitamin D levels, the unit of measurement is nanograms/milliliters.

  Baseline before supplementation, seven days and fourteen days after supplementation

• Serum Levels of Interleukin-6 (IL-6)

  Interleukin-6 will be quantified in the serum of each patients sample using the ELISA technique. IL-6 is a proinflammatory cytokine. The study aims to observe changes in IL-6 levels, which could be significantly altered by vitamin D supplementation according to preliminary results.

  Baseline before supplementation, seven days and fourteen days after supplementation

Secondary Outcomes (2)

• Intensity of headache

  Baseline before supplementation, seven days and fourteen days after supplementation

• Duration of fever in days

  Baseline before supplementation, seven days and fourteen days after supplementation

Study Arms (2)

Daily Vitamin D Supplementation Group

EXPERIMENTAL

This arm of the study involves daily administration of vitamin D to participants, with the dosage adjusted based on body weight and initial vitamin D levels, aiming to to investigate the efficacy of this regimen in improving vitamin D levels and reducing COVID-19 symptoms and IL-6, GPx and Von Willebrand Factor concentration.

Drug: vitamin D (cholecalciferol) supplementation

Monthly Bolus Vitamin D Supplementation Group

EXPERIMENTAL

This arm of the study consists of administering a monthly bolus dose of vitamin D, equivalent to the total daily dose accumulated over the month, divided into 4 daily doses on 4 consecutive days, to investigate the efficacy of this regimen in improving vitamin D levels and reducing COVID-19 symptoms and IL-6, GPx and Von Willebrand Factor concentration.

Drug: vitamin D (cholecalciferol) supplementation

Interventions

vitamin D (cholecalciferol) supplementation DRUG

This pilot clinical study administered and compared daily and bolus vitamin D dosing regimens to achieve and maintain optimal serum 25(OH)D levels in patients with COVID-19. The daily dose group received constant cholecalciferol supplementation (vitamin D supplementation), aimed at achieving more stable and non-peak 25(OH)D levels. In contrast, the bolus group received a one-month cumulative monthly dose, divided into 4 doses, administered on 4 consecutive days, which could result in rapid increases followed by gradual decreases in 25(OH)D levels. The daily dose of cholecalciferol was calculated using the following formula: Daily dose of cholecalciferol = \[Weight (kg) × desired increase in 25(OH)D (ng/ml) × 2.5\] - 10 . Bolus dose = (daily dose)(30 days)/4 doses

Daily Vitamin D Supplementation Group; Monthly Bolus Vitamin D Supplementation Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients hospitalized for severe COVID-19 clinical presentation in the "early stage," with a maximum of 9 days after the onset of the first symptoms and who have not progressed to the "active phase" (fever, cough, sore throat, diarrhea, loss of taste or smell, oxygen saturation \<92%, PaO2 / FiO2 \<300 mmHg, respiratory rate \>30 breaths per minute, or pulmonary infiltrates \>50%).
• Patients older than 18 years and younger than 65 years who have received at least 2 doses of the COVID-19 vaccine.
• Patients who agree to participate at the time of hospitalization and sign the informed consent.
• Patients with 25(OH)D levels below 40 ng/ml and without contraindications for Vitamin D3 supplementation.

You may not qualify if:

• Patients who, at the time of recruitment, have another comorbidity as the primary condition for which they were hospitalized and that places them at high risk of death (e.g., terminal cancer, postoperative patients, renal failure, liver disease, uncontrolled diabetes, patients with HIV, CMV, tuberculosis, traumatic brain injury, shock from any cause, etc.).
• Pregnant or breastfeeding patients.
• Patients who have received Vitamin D3 supplements greater than 800 IU/day, 15 days before recruitment.
• Patients with contraindications for Vitamin D3 supplementation, such as active granulomatous diseases (sarcoidosis, tuberculosis, lymphoma, Vitamin D3 metabolism disorders, hypercalcemia).
• History of kidney stones.
• Known Vitamin D3 hypervitaminosis or hypercalcemia.
• Known intolerance to Vitamin D3.
• Patients with extrapulmonary organ failure.
• Patients with 25(OH)D levels equal to or greater than 40 ng/ml.
• Patients who, at the time of recruitment, exhibit clear signs of "critical illness" due to COVID-19, such as organ failure requiring intensive care admission or who meet the criteria for mechanical ventilation due to oxygen desaturation: PaO2 \<60 mmHg (after supplemental oxygen), SpO2 \<88% (after supplemental oxygen), PaCO2 \>50 mmHg with pH \<7.32.
• Elimination Criteria:
• Patients who require major surgery after recruitment.
• Patients who develop contraindications to standard COVID-19 treatment.
• Patients who die before completing the three blood sample collections.
• Patients who receive an IL-6 blocking drug.

Sponsors & Collaborators

• Escuela Militar de Graduados de Sanidad, SEDENA: lead

Study Sites (1)

Instituto Nacional de Pediatría

Mexico City, 04530, Mexico

Location

MeSH Terms

Conditions

COVID-19; Cough; Dyspnea; Fatigue; Anxiety Disorders; Depression

Interventions

Vitamin D; Cholecalciferol; Dietary Supplements

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: September 19, 2024
• Study Start: April 29, 2022
• Primary Completion: March 28, 2024
• Study Completion: May 10, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

ME (1)