Cardiovascular Diseases
Conditions
Brief summary
The principal research objective is to determine whether inorganic nitrate in the form of beetroot juice compared to placebo control prevents the systemic inflammation that underlies typhoid vaccine-induced endothelial dysfunction
Detailed description
We wish to determine in a prospective manner whether inorganic nitrate affects the endothelial dysfunction induced by systemic inflammation. At baseline we will measure flow-mediated dilatation (FMD) and peripheral augmentation index, as well as aortic stiffness, as measured by pulse wave velocity (PWV). Volunteers will then receive \ 8 mmols of dietary nitrate or nitrate free placebo juice once daily for 6 days. After this, depending on availability, volunteers will receive a typhoid vaccine Typherix®, GlaxoSmithKline UK or Typhim Vi ™, AAH Pharmaceuticals Ltd). This vaccine generates a mild systemic inflammation that is associated with vascular dysfunction. All vascular function measures will be repeated at 8 hours and 32 hours after vaccine administration.
Interventions
BIOLOGICALTyphoid vaccine
The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution
DIETARY_SUPPLEMENTConcentrate beetroot Juice
140 ml containing \ 8 mmol of inorganic nitrate
DIETARY_SUPPLEMENTConcentrate beetroot Juice (Placebo)
140 ml which is nitrate-depleted
Sponsors
Queen Mary University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy volunteers 2. Aged 18-45 3. Volunteers who are willing to sign the consent form. 4. Normal resting blood pressure (\<140/90 mmHg)
Exclusion criteria
1. Healthy subjects unwilling to consent 2. Pregnant, or any possibility that a subject may be pregnant unless in the latter case a pregnancy test is performed with a negative result 3. History of any serious illnesses, including recent infections or trauma 4. Subjects taking systemic medication (other than the oral contraceptive pill) 5. Subjects with self-reported use of mouthwash or tongue scrapes 6. Subjects with recent (3 months) or current antibiotic use 7. Subjects with a history, or recent treatment of (within last 3 months) any oral condition (excluding caries), including gingivitis, periodontitis and halitosis 8. Subjects with a history of typhoid vaccination in the last 6 months 9. Subjects with any history of a blood-borne infectious disease such Hepatitis B or C virus, or HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow mediated dilatation | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) | Comparison of change in FMD from baseline after typhoid vaccination following inorganic nitrate versus placebo supplementation |
| Plasma nitrite concentration | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) | Comparison of change in plasma nitrite concentration following inorganic nitrate versus placebo supplementation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Markers of acute inflammation | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) | Comparison of change in peripheral markers of inflammation and leucocyte count following nitrate versus placebo supplementation |
| Pulse wave velocity | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) | Comparison of change in PWV from baseline after typhoid vaccination following nitrate versus placebo supplementation |
| Platelet reactivity | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) | Comparison of change in platelet reactivity from baseline after typhoid vaccination following nitrate versus placebo supplementation |
| Plasma nitrate concentration | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) | Comparison of change in plasma nitrate concentration following inorganic nitrate versus placebo supplementation |
Countries
United Kingdom
Outcome results
None listed