Eucaloric Ketogenic Diet in COVID-19 Cytokine Storm Syndrome

Study Overview
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Brief Summary
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Covid 19 pandemia is causing millions of deaths worldwide. To date, the evidence gathered suggests that the subgroup of patients who present the most serious clinical feature of COVID-19 could have a cytokine storm syndrome better defined as secondary hemophagocytic lymphohistiocytosis (sHLH), characterized by acute respiratory distress (ARDS) and septic shock, followed by multi-organ failure due to an excess of cytokines induced by the inflammatory response to the virus. The reduction of phagocytic hyperactivation represents a possible treatment for HLH. Lowering the availability of glucose, the only substrate of aerobic glycolysis and of the Warburg effect in activated macrophages, through the use of ketogenic diets could be a promising solution. Actually diet is not recognized as impacting on the evolution of COVID-19, however, scientific literature data show that a low carbohydrate and high lipid diet (ketogenic diet) can inhibit inflammation and lead to a clinical improvement of respiratory function. The hypothesis of this study is that the administration of a ketogenic diet could improve mortality, lower the access to ICU and the need of NIV. The plan is to enroll 50 patients with COVID 19 infection and administer a 1:4 ketogenic formula during hospitalization in order to verify these outcomes.

Official Title
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Randomized Open Controlled Clinical Trial to Evaluate the Effectiveness of a Eucaloric Ketogenic Nutrition in Comparison With a Standard Nutrition in Covid-19 Disease in Reducing Cytokine Storm Syndrome and ARDS

Conditions
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Covid19, Ketogenic Dieting

Intervention / Treatment
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* Other: Ketogenic diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: documented clinical diagnosis of COVID-19 supported by clinical features and by the positivity to at least one pharyngeal swab age ≥18 years informed written consent Exclusion Criteria: Type I diabetes Type II diabetes in therapy with insulin, sulphonylureas, repaglinide, GLP-1 analogues, SGLT2 inhibitors Recent acute cardiovascular event (within a month) Food allergies to diet components Any metabolic disorder capable of influencing gluconeogenesis Clinical history of severe hypertriglyceridemia with or without pancreatitis Pregnancy and/or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a controlled, randomized, open-label, clinical trial designed to determine whether a ketogenic diet,in comparison with a standard diet, improves mortality and reduces ventilator requirements or ICU access in patients with coronavirus disease. The study team will prospectively enroll 50 patients with COVID-19 infection administering a 4:1 ratio ketogenic formula (both enteral or parenteral) and 50 with standard diet
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic diet group<br>patients with COVID-19 feeding with a ketogenic diet (4.1 formula) | Other: Ketogenic diet<br>* Eucaloric Ketogenic diet % composition : protein (27%), lipids (67%), carbohydrates (6%: <30g/day). In pts in artificial nutrition : Eucaloric Ketogenic parenteral nutrition % composition : aminoacids (27%), lipids (67%), carbohydrates (6%: <30g/day)<br>|
| No Intervention: Standard diet group<br>patients with COVID-19 feeding with a standard diet | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate in the ketogenic group diet vs standard one |  | Up to nine months | 
| Access in Intensive Care Unit in the ketogenic group diet vs standard one |  | Up to nine months | 
| Need of Non Invasive Ventilation in the ketogenic group diet vs standard one |  | Up to nine months | 
| Combined endpoint mortality, ICU transfer or need for CPAP or intubation in the ketogenic group diet vs standard one |  | Up to nine months |