Plant Stanol Esters and COVID-19 Vaccination Response

Study Overview
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Brief Summary
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Plant stanols are known to lower low-density lipoprotein cholesterol (LDL-C). However, studies have suggested that these compounds also beneficially influence the immune system, e.g. increasing vaccine-specific antibody titers. BMI has previously been negatively associated to vaccination responses. If plant stanols indeed have beneficial effect on the immune system, people with overweight or obesity might benefit from consuming plant stanols prior to receiving the COVID-19 vaccination. The primary objective of this study is to demonstrate clinical benefits of consumption of plant stanols (delivered via products enriched with plant stanol esters) on the vaccination response to a COVID-19 vaccine in overweight or obese patients. The main study endpoint is vaccination response to a COVID-19 vaccine. Secondary endpoints include amongst others hematological, inflammatory and immunological parameters (e.g. hs-CRP, leukocyte differential count) and metabolic markers (e.g. blood lipid profiles, plasma glucose, serum insulin, HOMA-IR).

Official Title
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The Effect of Plant Stanol Ester Consumption on the Vaccination Response to a COVID-19 Vaccine

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Dietary Supplement: Plant stanol mini drinks
* Dietary Supplement: Placebo mini drinks
* Biological: COVID-19 vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women Aged 18 years or older BMI between 27 and 35 kg/m2 Currently not using products containing plant sterols or stanols (products with a cholesterol lowering claim of Becel ProActiv, Benecol, Danacol, store brands) Willing to abstain from products containing plant sterols or stanols during the study (products with a cholesterol lowering claim of Becel ProActiv, Benecol, Danacol, store brands) Willing to keep the intake of fish oil and vitamin supplements constant Exclusion Criteria: Already received COVID-19 vaccination Already had a positive test for COVID-19 (this includes all types of tests, e.g. PCR tests or antibody tests) Allergy to an ingredient of the mini drinks Having donated blood within one month prior to the start of the study, or planning to donate blood during the study Pregnant women Breastfeeding women Excessive alcohol use (>20 consumptions per week) Regular use of soft or hard drugs

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plant stanol group<br>This arm receives 4g of plant stanols per day (delivered as plant stanol esters) by consuming mini drinks (100 mL each). | Dietary Supplement: Plant stanol mini drinks<br>* Oat milk based mini drinks (100 mL) containing 2g plant stanols each (delivered as plant stanol esters).<br>Biological: COVID-19 vaccine<br>* First dose of one of the COVID-19 vaccines. Participants have to wait until they are invited to receive the vaccine by the government; this study does not interfere with national planning of the vaccines.<br>|
| Placebo Comparator: Placebo group<br>This arm receives mini drinks without added plant stanols (delivered as plant stanol esters). | Dietary Supplement: Placebo mini drinks<br>* Oat milk based mini drinks (100 mL) without added plant stanols (delivered as plant stanol esters).<br>Biological: COVID-19 vaccine<br>* First dose of one of the COVID-19 vaccines. Participants have to wait until they are invited to receive the vaccine by the government; this study does not interfere with national planning of the vaccines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine specific antibody titers | The response to the COVID-19 vaccine will be measured by quantifying specific antibody titers (vaccine specific IgG and IgM). These titers will be measured in blood samples collected weekly during the month after vaccination by suitable ELISAs. | Change T=0 and T= 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune parameters (1) | Cytokine production by PBMCs after stimulation with antiCD3-antiCD28 antiCD28 antibodies using the TruCulture system | T=-1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination | 
| Immune parameters (2) | hsCRP | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Leukocyte count | Number of leukocytes measured in EDTA plasma | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Leukocyte differential count | Number of subgroups of leukocytes measured in EDTA plasma | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Fasted metabolism (1) | Serum non-cholesterol sterols and stanols | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Fasted metabolism (2) | Serum lipid and lipoprotein profile | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Fasted metabolism (3) | Glucose metabolism (including e.g. plasma glucose, serum insulin and calculated HOMA-IR) | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Anthropometry (1) | Body weight | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Anthropometry (2) | Height | T=-1 (start study) | 
| Anthropometry (3) | Waist circumference | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Anthropometry (4) | Hip circumference | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Anthropometry (5) | Waist-to-hip ratio | T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Diet | Food frequency questionnaire is used to determine if the participants maintain their habitual diet and to determine if the participants do not consume plant stanols and/or sterols outside the intervention | T=-1 (start study) and T=4 weeks after vaccination (end study) | 
| Diary outcomes (1) | General illness | T=-1 (start study) until T=4 weeks after vaccination (end of study) | 
| Diary outcomes (2) | Side effects COVID-19 vaccine | T=0 (day before vaccination) until T=4 weeks after vaccination (end of study) | 
| Diary outcomes (3) | Medication intake | T=-1 (start study) until T=4 weeks after vaccination (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overweight, Obesity, COVID-19 vaccine, Immune system, Vaccination response