Diet and COVID-19 Vaccination

Study Overview
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Brief Summary
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Recently, obesity and excess visceral fat were shown to be major risk factors for the development of complications following Covid 19 infection. Recently, KDs have been suggested as possible weapons to tame the cytokine storm being described in those developing complications upon COVID-19 infection, and preclinical evidence strongly supports the hypothesis, with mouse models of COVID-19 infection in the elderly reporting strikingly better outcomes upon consumption of a KD. Short-term interventions that use low-calorie ketogenic diets may be prescribed for selected overweight or obese patients with type 2 diabetes or prediabetes. No data is available on the impact of a ketogenic diet on immune modulation following vaccination. We herein aim at investigating whether obesity and unhealthy body composition are associated with poor seroconversion following the upcoming COVID-19 vaccine administration, and whether consumption of a KD before and between COVID-19 vaccine doses leads to better immune response in obese subjects. 24 obese patients will be assigned to follow a LCKD regimen for 5 weeks.

Detailed Description
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Recently, obesity and excess visceral fat were shown to be major risk factors for the development of complications following Covid 19 infection. Recently, KDs have been suggested as possible weapons to tame the cytokine storm being described in those developing complications upon COVID-19 infection, and preclinical evidence strongly supports the hypothesis, with mouse models of COVID-19 infection in the elderly reporting strikingly better outcomes upon consumption of a KD. Short-term interventions that use low-calorie ketogenic diets may be prescribed for selected overweight or obese patients with type 2 diabetes or prediabetes. No data is available on the impact of a ketogenic diet on immune modulation following vaccination. We herein aim at investigating whether obesity and unhealthy body composition are associated with poor seroconversion following the upcoming COVID-19 vaccine administration, and whether consumption of a KD before and between COVID-19 vaccine doses leads to better immune response in obese subjects. 24 patients will be assigned to follow a low-calorie ketogenic diet (LCKD). Outcome measures will be antiSARS-CoV-2 antibodies, cell mediated response to SARS CoV-2, anthropometric parameters, vital signs, metabolic profile, and body composition. The patients will be assessed at baseline (T0) and every two weeks (T1, T2) as they receive both SARS Cov-2 vaccination doses up to 1 week after the second dose (T3) when they will be finally evaluated and carbohydrate reintroduction takes place. Patients will be given support and counselling to enhance their compliance. Anthropometric parameters such as body weight, blood pressure (systolic and diastolic), heart rate, waist and hip circumference will be measured at baseline (T0), every two weeks up to the end of the trial (T3). Blood and urine chemistry Complete Blood Count (CBC), electrolytes (chloride, calcium, potassium, sodium, magnesium), fasting glucose, insulin, lipids (total and fractionated cholesterol and triglycerides) and proteins, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), plasma creatinine, blood urea nitrogen (BUN), alanine transferase (AST), aspartate transaminase (ALT), uric acid, beta hydroxy butyrate and estimated Glomerular Filtration Rate (using the Modification of Diet in Renal Disease study equation MDRD-eGFR) will be determined AntiSARS-CoV-2 antibodies: antibodies will be quantified by enzyme-linked immunosorbent assay using the appropriate antigen at T3 and T4 in all arms. The cell mediated response to SARS CoV-2 will be analyzed by taking whole blood that will be stimulated with immune ligands. Data obtained will be expressed as mean values ±Standard Deviation (SD) and finally processed to ascertain whether statistical differences among them can be demonstrated, using appropriate methods. In particular, the analysis of variance (ANOVA) at different times will be used for efficacy and safety data, such as weight reduction, changes in anthropometric measures, and variation of the metabolic parameters. P values <0.05 will be considered statistically significant.

Official Title
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COVID-19 Vaccination in Subjects With Obesity: Impact of Metabolic Health and the Role of a Ketogenic Diet

Conditions
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Obesity

Intervention / Treatment
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* Dietary Supplement: Low Calorie Ketogenic Diet


Participation Criteria
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Eligibility Criteria
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BMI ≥35.0 kg/m2 with comorbidities or BMI≥40 Stable body weight (less than 5 kg self-reported change during the previous 3 months) Informed consent obtained before any trial-related activity takes place Exclusion criteria Stage 3-5 CKD (GFR<60 ml/min) Type 1 diabetes Uncontrolled type 2 diabetes Previous infection with SARS CoV-2 Immunodeficiency or immunomodulating treatment Treatment with anti-obesity medications or other medications potentially affecting body weight or SGLT2 inhibitors Pregnancy and lactation Previous gout episodes Cardio and cerebrovascular accidents in the preceding 12 months

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic Diet-obese<br>LCKD (1200-1400kcal/day) low in carbohydrates (<50g per day) with a moderate protein intake (1-1.5g/kg of ideal body mass) but otherwise no other dietary restrictions. The participants will be counselled by a trained nutritionist at baseline and every two weeks, and compliance will be assessed through a 3-day dietary recall at each follow up visit and capillary beta hydroxybutyrate levels as well as urinary acetoacetate levels. The follow up visits take place at the time of the first vaccine dose, two weeks after the first vaccine dose, one week after the second vaccine dose. Then, gradual reintroduction of carbohydrates will take place following the second vaccine dose. | Dietary Supplement: Low Calorie Ketogenic Diet<br>* The very low-carbohydrate diet will be hypo caloric and aim to provide less than 50 g of carbohydrates per day. the participants will be counseled to choose vegetarian and healthy sources of fat and protein and to avoid trans fat. Then, gradual reintroduction of carbohydrates will take place following the second vaccine dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AntiSARS-CoV-2 antibodies | antibodies will be quantified by enzyme-linked immunosorbent assay at week 0 and 5 | 5 weeks | 
| Cell mediated response to SARS CoV-2 | whole blood will be stimulated with immune ligands within 8 h from blood collection. | 5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight | Body weight will be obtained with the subjects wearing very light clothing and no shoes, and with an empty bladder. The same scale will be used throughout the study. The scale will be calibrated. | 5 weeks | 
| Waist Circumference | Waist circumference will be measured on subjects while semi clothed, standing with their feet close together and their weight equally distributed on each leg. Subjects will be asked to breath normally. Circumference will be taken at the midpoint between the lower rib margin and the iliac crest. | 5 weeks | 
| Triglycerides, glucose, insulin, ESR, CRP, ferritin | All biochemical parameters will be measured according to local laboratory standards. | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ketogenic Diet, COVID-19, VAT, Obesity