Here is the design of a clinical trial:

Official Title: 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

Included conditions:
- Cardiovascular Diseases
- Endothelial Dysfunction

Study Armgroups:
- {'label': 'Part A: Male healthy volunteers', 'type': 'EXPERIMENTAL', 'interventionNames': ['Biological: COVID-19 vaccine']}
- {'label': 'Part A: Female healthy volunteers', 'type': 'EXPERIMENTAL', 'interventionNames': ['Biological: COVID-19 vaccine']}
- {'label': 'Part B: Nitrate-rich beetroot juice', 'type': 'ACTIVE_COMPARATOR', 'description': 'Dietary Supplement: Concentrate beetroot Juice (70 ml) containing \\~5mmol of inorganic nitrate', 'interventionNames': ['Biological: COVID-19 vaccine', 'Biological: Concentrate beetroot Juice']}
- {'label': 'Part B: Nitrate-deplete beetroot juice', 'type': 'PLACEBO_COMPARATOR', 'description': 'Dietary Supplement: Concentrate beetroot Juice (70 ml) which is nitrate-depleted', 'interventionNames': ['Biological: COVID-19 vaccine', 'Biological: Nitrate-deplete beetroot juice']}

Interventions:
- {'type': 'BIOLOGICAL', 'name': 'COVID-19 vaccine', 'description': 'COVID-19 vaccine as offered by NHS England', 'armGroupLabels': ['Part A: Female healthy volunteers', 'Part A: Male healthy volunteers', 'Part B: Nitrate-deplete beetroot juice', 'Part B: Nitrate-rich beetroot juice']}
- {'type': 'BIOLOGICAL', 'name': 'Concentrate beetroot Juice', 'description': 'Beetroot juice containing approximately 5mmol/l nitrate', 'armGroupLabels': ['Part B: Nitrate-rich beetroot juice']}
- {'type': 'BIOLOGICAL', 'name': 'Nitrate-deplete beetroot juice', 'description': 'Beetroot juice with nitrate removed', 'armGroupLabels': ['Part B: Nitrate-deplete beetroot juice']}

Primary Outcomes:
- {'measure': 'Comparison of change in FMD from baseline between the sexes after COVID-19 vaccination', 'description': '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.', 'timeFrame': 'Up to 28 days'}
- {'measure': 'Comparison of change in FMD from baseline after COVID-19 vaccination following inorganic nitrate versus placebo supplementation', 'description': '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.', 'timeFrame': 'Up to 28 days'}
- {'measure': 'Comparison of change in plasma [NO2-] following inorganic nitrate versus placebo supplementation', 'description': '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.', 'timeFrame': 'Up to 28 days'}

Please estimate the sample size based on the assumption: 
For part A: 90% power, 10% dropout rate. For part B: 80% power for primary outcome, 90% power for sex differences, >95% power to detect a rise in [NO2−], 10% dropout rate.
Sample size determination and statistical analysis
        In this study, we aim to recruit 98 participants, with 30 healthy volunteers in part A and 64 in part B. This sample size will empower the study to test the primary endpoint.
        These numbers have been based upon our previous experience with typhoid vaccination which causes a reduction in FMD of ~ 1.5% absolute units which is a reduction of approximately 25% of the response [28]. We have previously identified sex differences in the response to typhoid vaccine, with a change from baseline of FMD of ââ0.5 (SD = 2.4) in men and 2.4 (SD = 2.5) in women [29]. For part A, using these data, if we use a conservative effect size of 25% less than that achieved in our previously published study, 13 participants are required in each group to provide 90% power for the primary outcome. To account for potential dropouts of ~ 10%, 15 participants will be recruited into each group and thus 30 volunteers in total. For the analysis of part A, a linear regression model will be used to compare changes in vascular dysfunction pre- to post-vaccination between the sexes, unadjusted and adjusted for important risk factors including age, body mass index, and baseline vessel diameter.
        Our unpublished preliminary data investigating the effects of dietary inorganic nitrate on vascular responses (FMD) has identified a decrease in FMD from baseline of 1.4 (SD = 1.5) with typhoid vaccine and with dietary nitrate intervention only 0.08 (SD = 1.7) [20]. Based on these data, for the primary outcome of change in FMD, 25 participants will be required in each group at an 80% power, to observe a difference between the intervention arms. To observe the differences between the sexes, 30 in each group provides a 90% power, which will also offer a > 95% power to detect a rise in [NO2â], as observed in previous studies [30]. To account for potential dropouts of ~ 10%, a total of 68 volunteers will be recruited. For the statistical analysis in part B, analysis of covariance (ANCOVA) will be used to compare the change in vascular dysfunction pre- to post-vaccination, between dietary nitrate and placebo control groups adjusting for pre-vaccination level, and to compare the change in plasma [NO2â] between the dietary nitrate and placebo control groups.
        Personal data will be stored in a secured site file and clinical notes in a paper CRF, which will be security locked and coded. Only the direct research team will have access to the trial CRF. The subject will be given a unique, single identifier which will be used to identify data and samples. Results data will only be stored, shared, analysed, transmitted, and presented in an anonymised form. Participant experience questionnaires will be completed and stored in the secure CRF. Reasons for drop-out or deviation from protocol will be detailed in full. Data quality will be assessed upon completion of the study and stored electronically. Confidentiality will be maintained through these secure measures before, during, and after the trial. Data access will be granted only to direct study members. Upon completion of the study, a fully blinded data analysis will be undertaken by a statistician.