Effect of Vitamin D Supplementation on Glutathione Peroxidase (GPx) Activity, Interleukin-6 (IL-6) Levels and Clinical Outcomes in Post-COVID-19 Patients (VITDPOSTCOVID)

The goal of this clinical trial is to evaluate the effectiveness of vitamin D supplementation in treating neuropsychiatric symptoms and improving antioxidant levels in individuals diagnosed with post-COVID-19 condition, a state known as long-COVID. These individuals are primarily adults who have recovered from severe COVID-19 and exhibit persistent symptoms. The main questions it aims to answer are:

Does vitamin D (cholecalciferol) supplementation decrease levels of anxiety and depression in patients with post-COVID-19 condition? Does vitamin D (cholecalciferol) supplementation increase glutathione peroxidase (GPx) activity in these patients? Researchers will compare the effects of daily versus bolus doses of vitamin D (cholecalciferol) to see if one method is more effective than the other in achieving sufficient vitamin D levels and improving clinical outcomes.

Participants will:

Be randomly assigned to receive either a daily dose or a bolus dose of vitamin D over an 8-week period.

Undergo blood tests to measure biochemical markers such as interleukin-6 (IL-6) and GPx before and two months after starting supplementation.

Have their lung function tested using spirometry and diffusing capacity for carbon monoxide.

Complete the Hospital Anxiety and Depression Scale to assess changes in anxiety and depression levels.

Study Overview

• Status: Completed
• Conditions: Post-COVID19 Condition
• Intervention / Treatment: Drug: vitamin D (cholecalciferol) supplementation

Detailed Description

This clinical trial investigates the potential therapeutic benefits of vitamin D supplementation in individuals experiencing persistent health issues following recovery from severe COVID-19, commonly referred to as post-COVID-19 condition or long-COVID. The study primarily focuses on the neuropsychiatric symptoms such as anxiety and depression and the antioxidant enzyme activity, specifically glutathione peroxidase (GPx), which plays a critical role in mitigating oxidative stress within the body.

The trial is designed as a pilot, randomized controlled trial, where participants are divided into two groups to receive vitamin D in different dosing regimens: a daily dose and a bolus dose, administered weekly. This method allows for an examination of the efficacy of dosage frequency on achieving optimal serum vitamin D levels, which are hypothesized to influence the biochemical pathways involved in inflammatory and oxidative processes.

During the study, participants' serum levels of 25-hydroxyvitamin D (25(OH)D), a marker for vitamin D status, are assessed to ensure they reach and maintain a target level that previous studies have associated with optimal immune function and reduced inflammation. The participants' initial vitamin D status is carefully evaluated to tailor the supplementation dose according to individual needs, following a formula that considers their weight and the desired increase in 25(OH)D levels.

The antioxidant capacity of participants is measured through the activity of GPx in the blood. This enzyme is crucial for reducing oxidative stress, which is linked to various chronic diseases and has been suggested to play a significant role in the severity and progression of post-COVID-19 symptoms. By measuring GPx activity before and after vitamin D supplementation, the study aims to provide insights into the effectiveness of vitamin D in enhancing antioxidant defenses in post-COVID patients.

Furthermore, the trial includes an evaluation of lung function using high-resolution computed tomography (HRCT) and standard pulmonary function tests, including spirometry and the diffusing capacity of the lung for carbon monoxide (DLCO). These assessments help to determine any improvements in respiratory health, which is often compromised in patients with long-term COVID-19 effects.

The impact of vitamin D on neuropsychiatric symptoms is assessed using the Hospital Anxiety and Depression Scale (HADS), a validated tool that rates the severity of anxiety and depression symptoms. This aspect of the study highlights the potential of vitamin D not just as a physical health supplement but also as a modulator of mental health, particularly in the context of the ongoing recovery from a severe infectious disease.

By conducting this trial, the researchers aim to shed light on the broader implications of vitamin D supplementation, not only as a means of improving vitamin D status but also as a potentially significant intervention for improving the quality of life and health outcomes in individuals suffering from long-term effects of COVID-19.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Enfermedades Respiratorias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Post-COVID-19 Condition: Patients must have been previously diagnosed with COVID-19 and continue to experience persistent symptoms after recovery.
• Age: Participants must be adults aged 18 years or older.
• Vitamin D Deficiency: Initial serum 25-hydroxyvitamin D levels below 40 ng/mL.
• Completed Hospital Treatment for COVID-19: Patients must have been discharged from hospital treatment for COVID-19 at least 12 months prior to the study.
• Ability to Give Informed Consent: Participants must be capable of understanding and willing to sign a consent form.
• Ability to Perform Required Tests: Participants must be physically able to undergo spirometry and other functional tests as required by the study protocol.

Exclusion Criteria:

• Reading and Writing Difficulties: Patients who have difficulties in reading and/or writing that would impede their understanding of the study requirements or communication with study staff.
• Inability to Perform Physical Tests: Patients unable to perform functional walk and spirometry tests.
• Untreated Chronic Non-Respiratory Diseases: Individuals suffering from untreated chronic diseases such as diabetes mellitus, systemic arterial hypertension, hypothyroidism, or epilepsy that could interfere with the study outcomes.
• Recent Use of Vitamin D Supplements: Patients who have taken vitamin D supplements within three months prior to the start of the study.
• Participation in Other Clinical Trials: Patients currently participating in other clinical trials that might conflict with this study's protocol.
• Pregnancy: Due to potential risks and lack of data on high-dose vitamin D supplementation during pregnancy, pregnant women will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daily Vitamin D Supplementation Group; 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 achieve and maintain optimal serum vitamin D levels	Drug: vitamin D (cholecalciferol) supplementation; This clinical pilot study administered and compared daily and bolus dosing regi-mens of vitamin D to achieve and maintain optimal serum levels of 25(OH)D in post-COVID patients. The daily dose group received constant and gradual supplementation of cholecalciferol, intended to achieve more stable 25(OH)D levels without peaks. Conversely, the bolus group received a weekly dose that could lead to rapid increases followed by gradual declines 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 .
Experimental: Weekly Bolus Vitamin D Supplementation Group; This arm of the study involves administering a weekly bolus dose of vitamin D, equivalent to the total daily dose accumulated over the week, to investigate the efficacy of this regimen in improving vitamin D levels and reducing post-COVID-19 symptoms.	Drug: vitamin D (cholecalciferol) supplementation; This clinical pilot study administered and compared daily and bolus dosing regi-mens of vitamin D to achieve and maintain optimal serum levels of 25(OH)D in post-COVID patients. The daily dose group received constant and gradual supplementation of cholecalciferol, intended to achieve more stable 25(OH)D levels without peaks. Conversely, the bolus group received a weekly dose that could lead to rapid increases followed by gradual declines 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 .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glutathione Peroxidase (GPx) Activity	This measure assesses the antioxidant enzyme activity level in the blood, indicating the body's capacity to reduce oxidative stress. Increased activity of GPx is expected as a result of vitamin D supplementation	Baseline and two months post-supplementation
Neuropsychiatric Symptoms (Anxiety and Depression)	The severity of anxiety and depression will be quantified using the Hospital Anxiety and Depression Scale (HADS). A decrease in HADS scores post-supplementation is anticipated.	Baseline and two months post-supplementation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Levels of Interleukin-6 (IL-6)	IL-6 is a pro-inflammatory cytokine. The study aims to observe changes in IL-6 levels, which might not be significantly altered by vitamin D supplementation as per preliminary findings.	Baseline and two months post-supplementation.
Lung Function Tests	Includes Forced Vital Capacity (FVC) and Forced Expiratory Volume in One Second (FEV1). Improvements in these parameters would suggest beneficial effects of vitamin D on lung health	Baseline and two months post-supplementation.
Serum 25-Hydroxyvitamin D Levels	This measure will confirm the efficacy of the vitamin D supplementation regimen in achieving and maintaining sufficient serum levels of vitamin D.	Baseline and two months post-supplementation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms of Cough, Dyspnea, and Fatigue	Assessment of respiratory and general symptoms associated with long-COVID to determine any subjective improvement post-vitamin D supplementation	Baseline and two months post-supplementation.

Collaborators and Investigators

• Sponsor: Escuela Militar de Graduados de Sanidad, SEDENA

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2022
• Primary Completion (Actual): April 20, 2023
• Study Completion (Actual): May 25, 2023

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 15, 2024
• First Posted (Actual): May 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: fatigue; depression; anxiety; vitamin D; cough; cholecalciferol; dyspnea; interleukin-6; Post-COVID-19 condition; glutathione peroxidase; long-COVID-19
• 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; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: C32-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Upon completion of the study, and after publication of the primary findings, the following Individual Participant Data will be made available:

Anonymized Participant Data: This includes all individual data collected during the trial, minus any personally identifiable information. Data types include:

Demographic information (age, gender, etc.) Clinical data (symptoms, disease severity, etc.) Treatment data (dosage received, treatment duration, etc.) Outcome data (response to treatment, side effects, etc.) Laboratory results (vitamin D levels, IL-6 levels, GPx activity, etc.).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No