A Double-blind, Randomised, Placebo-controlled Parallel Study to Investigate the Effect of Dietary Nitrate and Sex on COVID-19 Vaccine Induced Vascular Dysfunction in Healthy Men and Women
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Comparison of change in FMD from baseline between the sexes after COVID-19 vaccination
研究概览
简要总结
Inorganic nitrate can protect blood vessels from the damage that occurs during cardiovascular disease. Early experimental work suggests that nitrate-induced improvements in vascular function relate to the suppression of inflammatory pathways. Whether this protection against inflammation-induced damage to the blood vessel wall might also be functional in the setting of COVID-19 vaccination will be investigated.
Vascular function will be assessed before and after the healthy participant has received their COVID-19-vaccination. Whether there might be differences in the response to the vaccine between the sexes and whether a dietary nitrate intervention impacts upon the effects of vaccination will be investigated.
The study is in two parts:
Part A: To assess sex differences in the vascular response to COVID-19 vaccination.
Part B: To assess whether inorganic nitrate, in the form of dietary inorganic nitrate supplementation compared to placebo control, can raise circulating plasma nitrite levels and thereby prevent the systemic inflammation that causes vascular dysfunction.
详细描述
Whether the COVID-19 vaccine can be used to study endothelial dysfunction and whether inorganic nitrate might be useful in restoring the function of the endothelium in a scenario simulating the COVID-19 infection setting will be investigated.
Furthermore, sex differences in the vascular response to the COVID-19 vaccination will be investigated.
Design: A prospective randomised, double-blind, placebo-controlled trial.
Target population: A total of 98 healthy participants will be recruited. Part A: 30 participants (15 male, 15 female.) Part B: 68 participants (34 intervention, 34 placebo). Participants will be recruited prior to receiving the COVID-19 vaccination, via Barts Health NHS Trust approved vaccination hubs.
Setting: Equal numbers of healthy male and female volunteers, aged between 18 and 60 years of age, will be recruited. Following recruitment, participants will undergo baseline measurements of vascular function of flow mediated dilatation (FMD) and pulse wave analysis/velocity (PWA, PWV), in addition to haematological and clinical biochemical analyses. Volunteers will then be randomised into one of the 2 study Parts (Part A: sex differences in vascular response to COVID-19 vaccine, Part B: influence of dietary nitrate upon vascular responses to COVID-19 vaccine). If randomised to Part B, volunteers will be treated with 3 days of either 4-5mmol nitrate-containing beetroot juice or placebo. If randomised to Part A, the volunteers will not receive an intervention. On day 3, all participants will receive their COVID-19 vaccine. At 8±2hours after the vaccine, the participants will undergo repeat measurements of vascular function. A quality of life questionnaire will be obtained 28 days after the vaccine has been administered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers with a booking for COVID-19 vaccination slot as per government guidelines
- •Volunteers who are willing to sign the consent form
排除标准
- •Aged <18 or >60 years
- •Healthy subjects unwilling to consent
- •Pregnant, or any possibility that a subject may be pregnant
- •History of any serious illnesses, including recent infections or trauma
- •Subjects taking systemic medication (other than the oral contraceptive pill)
- •Subjects with self-reported use of mouthwash or tongue scrapes
- •Subjects with recent (2 weeks) or current antibiotic use
- •Subjects with a history, or recent treatment of (within last 3 months) any oral condition (excluding caries), including gingivitis, periodontitis and halitosis
- •Subjects with a history of COVID-19 vaccination
- •Subjects with any history of a blood-borne infectious
研究组 & 干预措施
Part A: Male healthy volunteers
干预措施: COVID-19 vaccine (Biological)
Part A: Female healthy volunteers
干预措施: COVID-19 vaccine (Biological)
Part B: Nitrate-rich beetroot juice
Dietary Supplement: Concentrate beetroot Juice (70 ml) containing ~5mmol of inorganic nitrate
干预措施: COVID-19 vaccine (Biological)
Part B: Nitrate-rich beetroot juice
Dietary Supplement: Concentrate beetroot Juice (70 ml) containing ~5mmol of inorganic nitrate
干预措施: Concentrate beetroot Juice (Biological)
Part B: Nitrate-deplete beetroot juice
Dietary Supplement: Concentrate beetroot Juice (70 ml) which is nitrate-depleted
干预措施: COVID-19 vaccine (Biological)
Part B: Nitrate-deplete beetroot juice
Dietary Supplement: Concentrate beetroot Juice (70 ml) which is nitrate-depleted
干预措施: Nitrate-deplete beetroot juice (Biological)
结局指标
主要结局
Comparison of change in FMD from baseline between the sexes after COVID-19 vaccination
时间窗: Up to 28 days
A measurement of brachial artery diameter using ultrasound (FMD, flow mediated dilatation) will be conducted at visits 2 and 3 (i.e. pre- and post-vaccine). This outcome measure will compare these 2 measurements, and change in FMD will be calculated as subtracting the value collected at visit 3 from visit 2, and expressed as a percentage (%). Comparisons will then be made between the sexes (i.e. males vs females) in Part A.
Comparison of change in FMD from baseline after COVID-19 vaccination following inorganic nitrate versus placebo supplementation
时间窗: Up to 28 days
A measurement of brachial artery diameter using ultrasound (FMD, flow mediated dilatation) will be conducted at visits 2 and 3 (i.e. pre- and post-vaccine). This outcome measure will compare these 2 measurements, and change in FMD will be calculated as subtracting the value collected at visit 3 from visit 2, and expressed as a percentage (%). Comparisons will then be made between intervention and placebo in Part B.
Comparison of change in plasma [NO2-] following inorganic nitrate versus placebo supplementation
时间窗: Up to 28 days
Quantification of \[NO2-\] will be made using ozone chemiluminescence. Samples of blood, urine and saliva will be acquired at visit 2 and visit 3 (i.e. pre- and post-vaccine). Measurement of \[NO2-\] will be made in all matrices at both timepoints, and a comparison will be made (for this we plan on using 2-way ANOVA, using GraphPad Prism statistics package) to compare time and intervention.
次要结局
- Comparison between the sexes in the systemic inflammatory response to COVID-19 vaccination(Up to 28 days)
- Comparison between nitrate and placebo with respect to endothelium independent vasodilation of the brachial artery(Up to 28 days)
- Comparison between nitrate and placebo with respect to inflammatory cell activation state(Up to 28 days)
- Comparison between nitrate and placebo with respect to circulating inflammatory mediators(Up to 28 days)
- Comparison between nitrate and placebo with respect to platelet function during systemic inflammation(Up to 28 days)