Covid19ketocovidietNCT04492228
Eucaloric Ketogenic Diet in COVID-19 Cytokine Storm Syndrome
A study testing Ketogenic diet in people with Covid19 and Ketogenic Dieting, run by Ospedale Policlinico San Martino at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Ketogenic Dieting
- What is being tested?
- Ketogenic diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Sep 2020to 30 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Samir Giuseppe Sukkar
Genova, 16132
Samir G Sukkar, MD, 00393356098178, samir.sukkar@hsanmartino.it
Livia Pisciotta, MD, 00393471055508, livia.pisciotta@unige.it
About this study
Official title: 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
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.
Read more
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.
- Conditions
- Covid19, Ketogenic Dieting
- Being tested
- Ketogenic diet
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic dietOther
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)
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic diet group | Experimental | patients with COVID-19 feeding with a ketogenic diet (4.1 formula) Receives: Other: Ketogenic diet |
| Standard diet group | No intervention | patients with COVID-19 feeding with a standard diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality rate in the ketogenic group diet vs standard one
Measured: Up to nine months
Access in Intensive Care Unit in the ketogenic group diet vs standard one
Measured: Up to nine months
Need of Non Invasive Ventilation in the ketogenic group diet vs standard one
Measured: Up to nine months
Combined endpoint "mortality, ICU transfer or need for CPAP or intubation" in the ketogenic group diet vs standard one
Measured: Up to nine months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2020
- Study start1 Sep 2020
- Primary completion31 Dec 2020 (estimated)
- Study completion30 May 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ospedale Policlinico San Martino
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sukkar Samir, MD, Ospedale Policlinico San Martino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04492228
- Sponsor's protocol ID
- KETOCOV-1
- Acronym
- ketocovidiet
- Status last verified
- Sep 2020
- First submitted
- 25 Jul 2020
- Last updated
- 30 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
PubMed 32192578Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.
PubMed 32007143Karakike E, Giamarellos-Bourboulis EJ. Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis. Front Immunol. 2019 Jan 31;10:55. doi: 10.3389/fimmu.2019.00055. eCollection 2019.
PubMed 30766533Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009 Apr;83(7):3039-48. doi: 10.1128/JVI.01792-08. Epub 2008 Nov 12.
PubMed 19004938Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ; SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003 May 15;348(20):1953-66. doi: 10.1056/NEJMoa030781. Epub 2003 Apr 10.
PubMed 12690092Kindler E, Thiel V. SARS-CoV and IFN: Too Little, Too Late. Cell Host Microbe. 2016 Feb 10;19(2):139-41. doi: 10.1016/j.chom.2016.01.012.
PubMed 26867172Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, Perlman S. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016 Feb 10;19(2):181-93. doi: 10.1016/j.chom.2016.01.007.
PubMed 26867177Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
PubMed 31986264Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, Bi Z, Zhao Y. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020 May;109(5):531-538. doi: 10.1007/s00392-020-01626-9. Epub 2020 Mar 11.
PubMed 32161990Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available.
PubMed 32125452Tate RM, Repine JE. Neutrophils and the adult respiratory distress syndrome. Am Rev Respir Dis. 1983 Sep;128(3):552-9. doi: 10.1164/arrd.1983.128.3.552. No abstract available.
PubMed 6351681Keatings VM, Barnes PJ. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med. 1997 Feb;155(2):449-53. doi: 10.1164/ajrccm.155.2.9032177.
PubMed 9032177Foucher P, Heeringa P, Petersen AH, Huitema MG, Brouwer E, Tervaert JW, Prop J, Camus P, Weening JJ, Kallenberg CG. Antimyeloperoxidase-associated lung disease. An experimental model. Am J Respir Crit Care Med. 1999 Sep;160(3):987-94. doi: 10.1164/ajrccm.160.3.9807139.
PubMed 10471629Johnson KJ, Fantone JC 3rd, Kaplan J, Ward PA. In vivo damage of rat lungs by oxygen metabolites. J Clin Invest. 1981 Apr;67(4):983-93. doi: 10.1172/jci110149.
PubMed 6894154Haegens A, Vernooy JH, Heeringa P, Mossman BT, Wouters EF. Myeloperoxidase modulates lung epithelial responses to pro-inflammatory agents. Eur Respir J. 2008 Feb;31(2):252-60. doi: 10.1183/09031936.00029307. Epub 2007 Dec 5.
PubMed 18057061
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04492228
- Acronym / sponsor ID
- ketocovidiet / KETOCOV-1
- Conditions
- Covid19, Ketogenic Dieting
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Ospedale Policlinico San MartinoUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 31 Dec 2020 (estimated)
- Study completion
- 30 May 2021 (estimated)
- First posted
- 30 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Ketogenic diet group | Experimental | Other: Ketogenic dietpatients with COVID-19 feeding with a ketogenic diet (4.1 formula) |
| Standard diet group | No intervention | –patients with COVID-19 feeding with a standard diet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketogenic dietEucaloric 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) | Other | Ketogenic diet group |
Primary outcome
Mortality rate in the ketogenic group diet vs standard one
Time frame: Up to nine months
Access in Intensive Care Unit in the ketogenic group diet vs standard one
Time frame: Up to nine months
Need of Non Invasive Ventilation in the ketogenic group diet vs standard one
Time frame: Up to nine months
Combined endpoint "mortality, ICU transfer or need for CPAP or intubation" in the ketogenic group diet vs standard one
Time frame: Up to nine months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2020.
- Background: PubMed 32192578Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
- Background: PubMed 32007143Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.
- Background: PubMed 30766533Karakike E, Giamarellos-Bourboulis EJ. Macrophage Activation-Like Syndrome: A Distinct Entity Leading to Early Death in Sepsis. Front Immunol. 2019 Jan 31;10:55. doi: 10.3389/fimmu.2019.00055. eCollection 2019.
- Background: PubMed 19004938Yoshikawa T, Hill T, Li K, Peters CJ, Tseng CT. Severe acute respiratory syndrome (SARS) coronavirus-induced lung epithelial cytokines exacerbate SARS pathogenesis by modulating intrinsic functions of monocyte-derived macrophages and dendritic cells. J Virol. 2009 Apr;83(7):3039-48. doi: 10.1128/JVI.01792-08. Epub 2008 Nov 12.
- Background: PubMed 12690092Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ; SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003 May 15;348(20):1953-66. doi: 10.1056/NEJMoa030781. Epub 2003 Apr 10.
- Background: PubMed 26867172Kindler E, Thiel V. SARS-CoV and IFN: Too Little, Too Late. Cell Host Microbe. 2016 Feb 10;19(2):139-41. doi: 10.1016/j.chom.2016.01.012.
- Background: PubMed 26867177Channappanavar R, Fehr AR, Vijay R, Mack M, Zhao J, Meyerholz DK, Perlman S. Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016 Feb 10;19(2):181-93. doi: 10.1016/j.chom.2016.01.007.
- Background: PubMed 31986264Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24.
- Background: PubMed 32161990Li B, Yang J, Zhao F, Zhi L, Wang X, Liu L, Bi Z, Zhao Y. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol. 2020 May;109(5):531-538. doi: 10.1007/s00392-020-01626-9. Epub 2020 Mar 11.
- Background: PubMed 32125452Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available.
- Background: PubMed 6351681Tate RM, Repine JE. Neutrophils and the adult respiratory distress syndrome. Am Rev Respir Dis. 1983 Sep;128(3):552-9. doi: 10.1164/arrd.1983.128.3.552. No abstract available.
- Background: PubMed 9032177Keatings VM, Barnes PJ. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med. 1997 Feb;155(2):449-53. doi: 10.1164/ajrccm.155.2.9032177.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketogenic diet in people with Covid19 and Ketogenic Dieting, run by Ospedale Policlinico San Martino at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Samir G Sukkar, MD (0105553985, samir.sukkar@hsanmartino.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality rate in the ketogenic group diet vs standard one (time frame: Up to nine months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04492228, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2020.