Magnesium and Vitamin D Combination for Post-COVID Syndrome
Study Details
Study Description
Brief Summary
The goal of this double-blind randomized controlled clinical trial is to determine the efficacy of the administration of magnesium chloride + vitamin D as an adjuvant in the treatment of post-Coronavirus Disease (COVID) syndrome.
The participants will be integrated: a) Intervention group that will receive 1 g of magnesium chloride (equivalent to 300 mg of elemental magnesium) + 4000 IU of vitamin D once a day, for four months. b) Control group that will receive inert placebo for four months.
The outcome variable will be the improvement of the post-COVID syndrome. At the beginning and end of the study, blood samples will be taken to determine serum levels of vitamin D, total magnesium, ionic magnesium, calcium, fasting glucose and lipid profile.
The evaluation of the efficacy and safety of the proposed intervention will be carried out by establishing the differences between the intervention and control groups.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Detailed Description
More than 50 signs and symptoms have been described that characterize the post-COVID syndrome, among them the early presence of fatigue, shortness of breath, cough, joint and chest pain. Later, the signs and symptoms that may occur are muscle pain, headache, tachycardia, loss of smell or taste, memory and concentration problems, difficulty falling asleep, skin rashes and hair loss.
Vitamin D is a fat-soluble vitamin whose best-known function is calcium and phosphate homeostasis, but it is also involved in multiple processes, including the regulation of the immune response. In vitro, vitamin D decreases viral replication, which is linked to its ability to stimulate innate immunity, increases the synthesis of cathelicidin and defensins, peptides that favor the preservation of the mucosa and enhance its protective effect against infection. In vivo, vitamin D decreases the expression of the cellular co-receptor dipeptidyl peptidase (DPP)-4/cluster of differentiation antigen 26 (CD26), which interacts with protein S, which decreases the penetration of the virus into the cell, contributes to the regulation of immunity, regulating excessive immune response, which is associated with an adverse prognosis, and interacts with the nuclear factor-kappa B (NF-kB) pathway, decreases the intensity of the Th1 response and the synthesis of proinflammatory cytokines, and increases the synthesis of anti-inflammatory cytokines.
Magnesium, through its calcium channel blocking effect, decreases the inflammatory response produced by the NF-kB cascade, reduces the production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) by monocytes and the expression of cytokines and inflammatory proteins. It influences both cell-mediated and humoral adaptive immunity, since it participates in the activation of leukocytes, the binding of antigens to macrophages, apoptotic regulation, and it reduces the production of superoxide anions.
The pathophysiology of the post-COVID syndrome is not precisely known, although it has been established that it is a disorder with inflammatory components, endothelial damage, and thromboembolism.
In this context, magnesium deficiency is associated with the development of the pro-inflammatory and pro-thrombotic response that generates a favorable microenvironment for the development of inflammation, endothelial damage and thromboembolism, components linked to the post-COVID syndrome. On the other hand, it has been described that patients with post-COVID present with vitamin D deficiency, a deficiency that contributes to the development of fatigue, anemia and chronic inflammation. In addition, there is interaction between magnesium and vitamin D, in such a way that the deficiency of the first contributes to the decrease in the synthesis of 25-hydroxy vitamin D and 1,25-hydroxy vitamin D and the number and activity of vitamin D receptors.
Therefore, it is plausible to assume that both magnesium and vitamin D play an important role in the development of post-COVID syndrome.
Goal. To determine the efficacy of the administration of magnesium chloride + vitamin D as an adjuvant in the treatment of post-COVID syndrome.
Methods. Double-blind randomized controlled clinical trial to which subjects diagnosed with post-COVID syndrome will be integrated. The participants will be integrated: a) Intervention group that will receive 1 g of magnesium chloride (equivalent to 300 mg of elemental magnesium) + 4000 IU of vitamin D once a day, for four months. b) Control group that will receive inert placebo for four months.
Men and women, aged 18 years or older, with a diagnosis of post-COVID syndrome, hypomagnesaemia and vitamin D insufficiency will be included. Having received magnesium or vitamin D supplements in the last 30 days, as well as treatment based on of steroids, will be exclusion criteria. The withdrawal of informed consent and adherence to the intervention less than 80% will be criteria for elimination.
The outcome variable will be the improvement of the post-COVID syndrome. At the beginning and end of the study, blood samples will be taken to determine serum levels of vitamin D, total magnesium, ionic magnesium, calcium, fasting glucose and lipid profile.
Statistic analysis. The evaluation of the efficacy and safety of the proposed intervention will be carried out by establishing the differences between the intervention and control groups, which will be estimated using the unpaired Student's t-test for analysis of the parametric variables (Mann-Whitney U for non-parametric variables) and Chi-Square (Fisher's exact test) for the analysis of categorical variables.
Intragroup differences will be estimated using the paired Student's t-test. Even when it is assumed that the confounding variables will be controlled by the randomization process; Additionally, a stratified analysis will be carried out by those confounding variables that in the bivariate analysis show significant differences.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Intervention group Will receive 1.2 g of magnesium chloride (equivalent to 360 mg of magnesium elemental) + 4000 IU of vitamin D once a day, for four months. |
Dietary Supplement: Magnesium chloride
Each 650 mg capsule contains 340 mg of magnesium chloride, which must be ingested twice a day with aliments.
Other Names:
Dietary Supplement: Vitamin D
Each tablet contains 4000 IU of vitamin D, and must be ingested a pill per night.
Other Names:
|
Placebo Comparator: Control group. Will receive inert placebo for four months. |
Dietary Supplement: Inert placebo
Instead of dietary supplements, sodium bicarbonate as inert placebo will be administered twice a day in 650 mg capsules.
|
Outcome Measures
Primary Outcome Measures
- Change from Baseline Post-COVID syndrome symptoms at 4 months [First control date, and four months after treatment initiation.]
The presence of two or more of the following signs and/or symptoms will be considered a suspicion of post-COVID syndrome: Fatigue, shortness of breath, cough, joint pain, chest pain, muscle pain, headache, tachycardia, arrhythmias, loss of smell, loss of taste, memory problems, concentration problems, depression, anxiety, insomnia, skin rashes, hair loss.
- Change from Baseline Post-COVID Functional Status at 4 months [First control date, and four months after treatment initiation.]
Post-COVID Functional Status Scale
- Change from Baseline Serum vitamin D levels at 4 months [First control assessment, and four months after treatment initiation.]
Recovery of serum vitamin D levels from deficiency (< 30 ng/mL) to normally (30 - 100 ng/mL). The serum concentration of the 25 OH vitamin D fraction will be determined by the enzyme-linked immunosorbent assay (ELISA) method, the serum levels of magnesium and calcium by colorimetric techniques (A15 Clinical Analyzer, Biosystems, USA).
- Change from Baseline Serum Magnesium levels at 4 months [First control assessment, and four months after treatment initiation.]
Recovery of serum magnesium levels from deficiency (< 2.0 mg/dL) to normally (2.0 - 2.5 mg/dL).
- Change from Baseline Mental State levels at 4 months [First control date, and four months after treatment initiation.]
Mini Mental State Examination
- Change from Baseline Anxiety Symptoms at 4 months [First control date, and four months after treatment initiation.]
Beck Anxiety Inventory
- Change from Baseline Depression Symptoms at 4 months [First control date, and four months after treatment initiation.]
Beck Depression Inventory
- Change from Baseline Post-traumatic Stress Symptoms at 4 months [First control date, and four months after treatment initiation.]
Severity of Post-traumatic Stress Symptoms
- Change from Baseline Dyspnea Symptoms at 4 months [First control date, and four months after treatment initiation.]
modified Medical Research Council (mMRC) dyspnea scale
Secondary Outcome Measures
- Change from Baseline Fasting Blood Glucose levels at 4 months [First control assessment, and four months after treatment initiation.]
Normal values: 70 - 100 mg/dL
- Change from Baseline Serum Lipid Profile at 4 months [First control assessment, and four months after treatment initiation.]
Normal values: total cholesterol 100 - 200 mg/dL; HDL-cholesterol 40 - 60 mg/dL; triglycerides 50 - 150 mg/dL.
- Change from Baseline Serum Calcium levels at 4 months [First control assessment, and four months after treatment initiation.]
Normal values: 8.4 - 10.2 mg/dL
- Change from Baseline Serum Creatinine levels at 4 months [First control assessment, and four months after treatment initiation.]
Normal values: 0.5 - 1.2 mg/dL
Eligibility Criteria
Criteria
Inclusion Criteria:
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Men and women aged 18 or older.
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Previous diagnosis of COVID-19, confirmed by Real Time Polymerase Chain Reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
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Diagnosis of post-COVID syndrome
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Hypomagnesemia
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Vitamin D deficiency
Exclusion Criteria:
- Subjects who have received magnesium and/or vitamin D supplements in the last 30 days
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Biomedical Research Unit. IMSS. Durango | Durango | Dgo | Mexico | 34067 |
Sponsors and Collaborators
- Coordinación de Investigación en Salud, Mexico
- Consejo de Ciencia y Tecnología del Estado de Durango
Investigators
- Principal Investigator: Fernando Guerrero, PhD, Instituto Mexicano del Seguro Social
- Study Chair: Gerardo Martínez, PhD, Instituto Mexicano del Seguro Social
- Study Chair: Luis Simental, PhD, Instituto Mexicano del Seguro Social
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Centers for Disease Control and Prevention
- Patient-Led Research Collaborative. Report: What Does COVID-19 Recovery Actually Look Like? An Analysis of the Prolonged COVID-19 Symptoms Survey by Patient-Led Research Team
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