Keto-diet for Intubated Critical Care COVID-19 (KICC-COVID19)

• ClinicalTrials.gov Identifier: NCT04358835
• Recruitment Status: Withdrawn
• First Posted: April 24, 2020
• Last Update Posted: August 25, 2020
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

Brief Summary:

Coronavirus disease (COVID-2019) is a devastating viral illness that originated in Wuhan China in late 2019 and there are nearly 2 million confirmed cases. The mortality rate is approximately 5% of reported cases and over half of patients that require mechanical ventilation for respiratory failure. As the disease continues to spread, strategies for reducing duration of ventilator support in patients with COVID-19 could significantly reduce morbidity and mortality of these individuals and future patients requiring this severely limited life-saving resource. Methods to improve gas exchange and to reduce the inflammatory response in COVID-19 are desperately needed to save lives.

The ketogenic diet is a high fat, low carbohydrate, adequate-protein diet that promotes metabolic ketosis (ketone body production) through hepatic metabolism of fatty acids. High fat, low carbohydrate diets have been shown to reduce duration of ventilator support and partial pressure carbon dioxide in patients with acute respiratory failure. In addition, metabolic ketosis reduces systemic inflammation. This mechanism could be leveraged to halt the cytokine storm characteristic of COVID-19 infection.

The hypothesis of this study is that the administration of a ketogenic diet will improve gas exchange, reduce inflammation, and duration of mechanical ventilation. The plan is to enroll 15 intubated patients with COVID 19 infection and administer a 4:1 ketogenic formula during their intubation.

Condition or disease	Intervention/treatment	Phase
COVID-19	Dietary Supplement: Ketogenic diet; Other: standard of care	Not Applicable

Detailed Description:

Coronavirus disease (COVID-2019) is a devastating viral illness that originated in Wuhan China in late 2019. The number of confirmed cases worldwide has nearly reached 2 million and more than 125,000 people have died. Early studies from Wuhan reported a mortality rate of 2-3% with lower rates in surrounding provinces as the disease spread (closer to 0.7% of confirmed cases). One hypothesized cause for the higher mortality rate in Wuhan compared to surrounding regions was the rapid "surge" of COVID-19 infections before the disease was identified and social distancing implemented. Critically ill patients developed acute respiratory distress syndrome with inflammatory pulmonary edema and life-threatening hypoxemia requiring mechanical ventilation. This resulted in a significant strain on health-care resources such as availability of mechanical ventilators to treat patients with acute respiratory failure. As the disease spreads worldwide, strategies for reducing duration of ventilator support in patients with COVID-19 could significantly reduce morbidity and mortality of these individuals and future patients requiring this severely limited life-saving resource.

Alterations in macronutrient composition may be leveraged to improve ventilation and inflammation in COVID-19 patients. The ketogenic diet is a high fat, low carbohydrate, adequate protein diet that promotes ketone body production through hepatic metabolism of fatty acids. High fat, low carbohydrate diets have been shown to reduce duration of ventilator support and partial pressure carbon dioxide in patients with acute respiratory failure. Switching from glucose to fat oxidation lowers the respiratory quotient, thereby reducing the amount of carbon dioxide produced. This reduces ventilator demands and may improve oxygenation by lowering alveolar carbon dioxide levels, ultimately reducing time on mechanical ventilation. A study published in 1989 compared 10 participants intubated for acute respiratory failure and randomized to a high-fat, low carbohydrate diet and 10 participants receiving a standard isocaloric, isonitrogenous diet and showed a decrease in the partial pressure of carbon dioxide of 16% in the ketogenic diet group compared to a 4% increase in the standard diet group (p=0.003). The patients in the high-fat diet group had a mean of 62 fewer hours on a ventilator (p = 0.006) compared to the control group.

The high-fat diet used in the study had a ratio of 1.2:1 fat to protein and carbohydrate combined in grams. The ketogenic diet, which has been used safely and effectively in patients with chronic epilepsy for nearly one century and more recently in critically ill, intubated patients for the management of refractory and super-refractory status epilepticus has a 4:1 ratio (90% fat kilocalories). While a 1:1 ratio diet can produce a state of mild metabolic ketosis (typically ~ 1 mmol/L of the ketone body betahydroxybutyrate, measured in serum), a higher 4:1 ratio ketogenic diet can produce higher ketone body betahydroxybutyrate levels and more rapidly (up to 2 mmol/L within 24 hours of initiation). One study of obese patients treated with ketogenic diet reported that increases in ketone body production correlated with a lower partial pressure of carbon dioxide levels. A more recent study showed that patients with refractory epilepsy had a reduction in the respiratory quotient and increased fatty acid oxidation without a change in the respiratory energy expenditure with chronic use of the ketogenic diet. These findings were replicated in healthy subjects on ketogenic diet compared to a control group and patients on a ketogenic diet also had a significant reduction in carbon dioxide output and partial pressure of carbon dioxide. The authors concluded that a ketogenic diet may decrease carbon dioxide body stores and that use of a ketogenic diet may be beneficial for patients with respiratory failure. Even in patients without hypercapnia (primarily hypoxic respiratory failure), lowering carbon dioxide production permits lowering tidal volumes - a cornerstone of acute respiratory distress syndrome management.

In addition to reducing the partial pressure of carbon dioxide, metabolic ketosis reduces systemic inflammation. This mechanism could be leveraged to halt the cytokine storm characteristic of COVID-19 infection. Several studies provide evidence that pro-inflammatory cytokine production is significantly reduced in animals fed a ketogenic diet in a variety of disease models. In a rodent model of Parkinson's disease, mice were found to have significantly decreased levels of pro-inflammatory, macrophage secreted cytokines interleukin-1β, interleukin-6, and Tumor necrosis factor-alpha after 1 week of treatment with a ketogenic diet. Likewise, rats pretreated with a ketogenic diet prior to injection with lipopolysaccharide to induce fever did not experience an increase in body temperature or interleukin-1β, while significant increases were seen in control animals not pretreated with a ketogenic diet. In a mouse model of NLRP3-mediated diseases as well as human monocytes, the ketone body beta-hydroxybutyrate inhibited the NLRP3 inflammasome-mediated production of interleukin-1β and interleukin-18. These findings have been replicated in several recent animal studies and preliminary studies in humans. The hypothesis of this study is that through induction of metabolic ketosis combined with carbohydrate restriction, a ketogenic diet is protective against the cytokine storm in COVID-19. With its carbon dioxide-lowering and anti-inflammatory properties, a ketogenic diet may become an important component of the acute respiratory distress syndrome arsenal with immediate relevance to the current COVID-19 pandemic.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a single-center, open-label, clinical trial designed to determine whether a ketogenic diet improves gas exchange and reduces ventilator requirements in patients with coronavirus disease intubated for respiratory failure. The study team will prospectively enroll 15 intubated patients with COVID-19 infection and administer a 4:1 ratio enteral ketogenic formula within 48 hours of intubation. This study will compare outcomes to a retrospective cohort of intubated patients with COVID-19 who did not receive ketogenic diet. As other clinical trials begin, co-administration of other therapies as well as standard care treatments will be recorded. In addition, the study will compare clinical outcomes with patients receiving exclusively standard clinical care.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Keto-diet for Intubated Critical Care COVID-19 (KICC-COVID19)
• Estimated Study Start Date: September 1, 2020
• Estimated Primary Completion Date: September 1, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intubated patients with COVID-19 on a ketogenic diet only; 4:1 ketogenic diet formula	Dietary Supplement: Ketogenic diet; 4:1 ratio enteral ketogenic formula within 48 hours of intubation; Other: standard of care; standard of care/supportive therapy

Outcome Measures

Primary Outcome Measures :

1. Change in the partial pressure of carbon dioxide (PaCO2) [ Time Frame: Daily until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   PaCO2 is the partial pressure of carbon dioxide Units: millimeters of mercury

Secondary Outcome Measures :

1. Change in minute ventilation [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Minute ventilation is the product of respiratory rate and tidal volume. Units: Liter per minute
2. Change in respiratory system compliance [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]

   Respiratory system compliance measures the extent to which the lungs will expand.

   In a ventilated patient, compliance can be measured by dividing the delivered tidal volume by the [plateau pressure minus the total peep]. Units: liter/centimeter of water

3. Change in driving pressure [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Driving pressure is a measure of the strain applied to the respiratory system and the risk of ventilator-induced lung injuries Driving pressure = Plateau pressure - Total Positive end-expiratory pressure (PEEP) Units: centimeter of water
4. Change in ventilator synchrony [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Ventilator synchrony is the match between the patient's neural inspiratory time and the ventilator insufflation time
5. Change in mean arterial pressure [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Mean arterial pressure is the average pressure in a patient's arteries during one cardiac cycle. Mean arterial pressure = diastolic blood pressure +[1/3(systolic blood pressure - diastolic blood pressure)] Units: millimeter of mercury
6. Change in the fraction of inspired oxygen percentage of oxygen (FiO2) [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]

   FiO2: Fraction of Inspired Oxygen Percentage of oxygen in the air mixture that is delivered to the patient.

   Units: %

7. Change in the partial pressure of carbon dioxide (PaO2) to the fraction of inspired oxygen percentage of oxygen (FiO2) ratio [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]

   PaO2/FiO2 ratio is the ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen.

   Units: millimeter of mercury

8. Change in hydrogen ion activity (pH) [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   pH measures hydrogen ion activity. It is a conventional part of every arterial blood gas determination pH: no units.
9. Change in Bicarbonate (HCO3) [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Bicarbonate is a conventional part of every arterial blood gas determination Units: milliequivalents/Liter
10. Change in red blood cell count [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Red blood cell count measure anemia or hypoglycemia. Units: cells per liter
11. Change in white blood cell count [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    White blood cell count evaluates leukopenia or leukocytosis. Units: cells/liter
12. Change in white cell differential [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    White cell differential shows the amount of neutrophils, lymphocytes, basophils, eosinophils and may give some clue of the type of infection. Units: %
13. Change in hemoglobin levels [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Hemoglobin is an indirect way to measure red blood cells. Units: gram/deciliter
14. Change in hematocrit [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Hematocrit measures the volume percentage of red blood cells in blood. Units: %
15. Change in mean cell volume [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Mean cell volume is a measure of the average volume of a red blood corpuscle. Units: femtoliters
16. Change in mean cell hemoglobin [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Mean cell hemoglobin is the average mass of hemoglobin per red blood cell in a sample of blood. Units: picograms
17. Change in mean cell hemoglobin concentration [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Mean cell hemoglobin concentration is the average concentration of hemoglobin in a given volume of blood. Units: %
18. Change in platelet count [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Platelet count measures the number of platelets in the blood and determines thrombocytopenia or thrombocytosis. Units: platelets/liter
19. Change in red cell distribution width [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Red cell distribution width is a measure of the range of variation of red blood cell volume. Units: no units
20. Change in blood albumin level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Liver function test Units: gram/deciliter
21. Change in serum alkaline phosphatase level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Liver function test Units: international units/liter
22. Change in serum aspartate transaminase level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Liver function test Units: international units/liter
23. Change in serum alanine aminotransferase level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Liver function test Units: international units/liters
24. Change in blood urea nitrogen levels [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Kidney function test Units: milligram/deciliter
25. Change in serum calcium level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Kidney function test Units: milligram/deciliter
26. Change in serum chloride level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Kidney function test Units: millimole/liter
27. Change in serum potassium level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Kidney function test Units: millimole/liter
28. Change in serum creatinine level [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Kidney function test Units: gram/deciliter
29. Date patient is re-intubated or need mechanical ventilation for a second time [ Time Frame: Up to 10 days ]
    If the patient needs mechanical ventilation for a second time, this information will be collected.
30. Length of intensive care unit stay [ Time Frame: Up to 10 days ]
    Time from intensive care unit admission until death or transfer to hospital bed.
31. The total hospital stay [ Time Frame: Up to 10 days ]
    Time from hospital admission to discharge from the hospital. This information will be collected.
32. Disposition at discharge [ Time Frame: Up to 10 days ]
    Once the patient feels better and can leave the hospital, he/she will be discharged. The place of discharge (e.g. home, rehab facility, nursing home, etc), time and date will be collected.
33. Change in heart rate [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Heart rate: is the number of times a person's heart beats per minute
34. Change in the dosage of vasopressor medication [ Time Frame: every 6 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Units: milligram

Other Outcome Measures:

1. Change in total blood cholesterol level [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Units: milligram/deciliter
2. Change in blood low-density lipoprotein level [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Units: milligram/deciliter
3. Change in blood high-density lipoprotein level [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Units: milligram/deciliter
4. Change in blood triglycerides level [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Units: milligram/deciliter
5. Change in blood glucose level [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Glucose: sugar in blood. Units: millimole/liter
6. Change in blood glucagon level [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Glucagon: hormone release by pancreas that increase concentration of glucose in blood. Units: nanogram/liter
7. Change in blood free fatty acids level [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Free fatty acids are fatty acids that are produced from triglycerides and are measure in blood.
8. Change in blood insulin levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Hormone that regulates glucose. Units: insulin units/liter
9. Change in blood leptin levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
   Leptin helps regulate and alter long-term food intake and energy expenditure. Units: nanogram/deciliter
10. Change in blood insulin like growth factor 1 levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Units: nanomole/liter
11. Change in blood C-reactive protein levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    C-reactive protein is a protein made by the liver that measures inflammation (e.g. pancreatitis). Units: microgram/milliliter
12. Change in blood interleukin-1β levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Cytokines are signaling molecules that measure inflammation.
13. Change in blood interleukin-6 levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Cytokines are signaling molecules that measure inflammation.
14. Change in blood interleukin-18 levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Cytokines are signaling molecules that measure inflammation.
15. Change in blood tumor necrosis factor alpha levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Cytokines are signaling molecules that measure inflammation.
16. Change in blood C-C motif chemokine ligand 2 (CCL2) levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Chemokine that mediates inflammation.
17. Change in blood C-C motif chemokine ligand 3 (CCL3) levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Chemokine that mediates inflammation.
18. Change in blood C-C motif chemokine ligand 4 (CCL4) levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Chemokine that mediates inflammation.
19. Change in blood B cell-attracting chemokine 1 (CXCL13) levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Chemokine that mediates inflammation.
20. Change in blood ferritin levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Ferritin stores iron inside of cells. Units: nanogram/milliliter
21. Change in blood betahydroxybutyrate levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Units: millimole/liter
22. Change in blood urine acetoacetate levels [ Time Frame: At baseline and every 24 hours until the patient is wean off the ventilator or die, whichever came first, assessed up to 10 days ]
    Units: millimole/liter

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients age 18 and older.
• COVID-19 positive and respiratory failure requiring intubation
• Legally authorized representative

Exclusion Criteria:

• Unstable metabolic condition
• Liver failure
• Acute Pancreatitis
• Inability to tolerate enteral feeds, ileus, gastrointestinal bleeding
• Known Pregnancy
• Received propofol infusion within 24 hours
• Known fatty acid oxidation disorder or pyruvate carboxylase deficiency

Contacts and Locations

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Mackenzie Cervenka, MD; Johns Hopkins University

More Information

Additional Information:

Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020 

Publications:

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McDonald TJW, Henry-Barron BJ, Felton EA, Gutierrez EG, Barnett J, Fisher R, Lwin M, Jan A, Vizthum D, Kossoff EH, Cervenka MC. Improving compliance in adults with epilepsy on a modified Atkins diet: A randomized trial. Seizure. 2018 Aug;60:132-138. doi: 10.1016/j.seizure.2018.06.019. Epub 2018 Jun 22.

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Tagliabue A, Bertoli S, Trentani C, Borrelli P, Veggiotti P. Effects of the ketogenic diet on nutritional status, resting energy expenditure, and substrate oxidation in patients with medically refractory epilepsy: a 6-month prospective observational study. Clin Nutr. 2012 Apr;31(2):246-9. doi: 10.1016/j.clnu.2011.09.012. Epub 2011 Oct 20.

Rubini A, Bosco G, Lodi A, Cenci L, Parmagnani A, Grimaldi K, Zhongjin Y, Paoli A. Effects of Twenty Days of the Ketogenic Diet on Metabolic and Respiratory Parameters in Healthy Subjects. Lung. 2015 Dec;193(6):939-45. doi: 10.1007/s00408-015-9806-7. Epub 2015 Sep 26. Erratum In: Lung. 2016 Nov 1;:

Ruskin DN, Ross JL, Kawamura M Jr, Ruiz TL, Geiger JD, Masino SA. A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington's disease. Physiol Behav. 2011 Jul 6;103(5):501-7. doi: 10.1016/j.physbeh.2011.04.001. Epub 2011 Apr 9.

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Schreck KC, Lwin M, Strowd RE, Henry-Barron BJ, Blakeley JO, Cervenka MC. Effect of ketogenic diets on leukocyte counts in patients with epilepsy. Nutr Neurosci. 2019 Jul;22(7):522-527. doi: 10.1080/1028415X.2017.1416740. Epub 2017 Dec 18.

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Dupuis N, Curatolo N, Benoist JF, Auvin S. Ketogenic diet exhibits anti-inflammatory properties. Epilepsia. 2015 Jul;56(7):e95-8. doi: 10.1111/epi.13038. Epub 2015 May 23.

Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nat Med. 2015 Mar;21(3):263-9. doi: 10.1038/nm.3804. Epub 2015 Feb 16.

Bae HR, Kim DH, Park MH, Lee B, Kim MJ, Lee EK, Chung KW, Kim SM, Im DS, Chung HY. beta-Hydroxybutyrate suppresses inflammasome formation by ameliorating endoplasmic reticulum stress via AMPK activation. Oncotarget. 2016 Oct 11;7(41):66444-66454. doi: 10.18632/oncotarget.12119.

Deora V, Albornoz EA, Zhu K, Woodruff TM, Gordon R. The Ketone Body beta-Hydroxybutyrate Does Not Inhibit Synuclein Mediated Inflammasome Activation in Microglia. J Neuroimmune Pharmacol. 2017 Dec;12(4):568-574. doi: 10.1007/s11481-017-9754-5. Epub 2017 Aug 23.

Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD. beta-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Rep. 2017 Feb 28;18(9):2077-2087. doi: 10.1016/j.celrep.2017.02.004.

Yamanashi T, Iwata M, Kamiya N, Tsunetomi K, Kajitani N, Wada N, Iitsuka T, Yamauchi T, Miura A, Pu S, Shirayama Y, Watanabe K, Duman RS, Kaneko K. Beta-hydroxybutyrate, an endogenic NLRP3 inflammasome inhibitor, attenuates stress-induced behavioral and inflammatory responses. Sci Rep. 2017 Aug 9;7(1):7677. doi: 10.1038/s41598-017-08055-1.

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Brozova K, Broz J. The risk of hypoglycemia and the ketogenic diet for super-refractory status epilepticus patients. Brain Dev. 2019 Sep;41(8):740. doi: 10.1016/j.braindev.2019.02.008. Epub 2019 Feb 22. No abstract available.

Cervenka MC, Henry BJ, Felton EA, Patton K, Kossoff EH. Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges. Epilepsy Behav. 2016 May;58:61-8. doi: 10.1016/j.yebeh.2016.02.038. Epub 2016 Apr 6.

van der Louw EJ, Williams TJ, Henry-Barron BJ, Olieman JF, Duvekot JJ, Vermeulen MJ, Bannink N, Williams M, Neuteboom RF, Kossoff EH, Catsman-Berrevoets CE, Cervenka MC. Ketogenic diet therapy for epilepsy during pregnancy: A case series. Seizure. 2017 Feb;45:198-201. doi: 10.1016/j.seizure.2016.12.019. Epub 2016 Dec 26.

Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Cross JH, Dahlin MG, Donner EJ, Guzel O, Jehle RS, Klepper J, Kang HC, Lambrechts DA, Liu YMC, Nathan JK, Nordli DR Jr, Pfeifer HH, Rho JM, Scheffer IE, Sharma S, Stafstrom CE, Thiele EA, Turner Z, Vaccarezza MM, van der Louw EJTM, Veggiotti P, Wheless JW, Wirrell EC; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018 May 21;3(2):175-192. doi: 10.1002/epi4.12225. eCollection 2018 Jun.

Correction to Lancet Respir Med 2020; published online Feb 21. https://doi.org/10.1016/S2213-2600(20)30079-5. Lancet Respir Med. 2020 Apr;8(4):e26. doi: 10.1016/S2213-2600(20)30103-X. Epub 2020 Feb 28. No abstract available.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT04358835
• Other Study ID Numbers: IRB00247383
• First Posted: April 24, 2020
• Last Update Posted: August 25, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johns Hopkins University:

ketogenic diet; Intensive care; COVID-19; Mechanical ventilation; Intubated patients; coronavirus

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases