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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
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 TypherixĀ®, GlaxoSmithKline UK or Typhim Vi ā¢, 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nitrate-rich beetroot juice | Active Comparator | Biological: Typhoid vaccine The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution Other Name: Typhim ViĀ® Dietary Supplement: Concentrate beetroot Juice 140 ml containing ~8 mmol of inorganic nitrate |
|
| Nitrate-deplete beetroot juice | Placebo Comparator | Biological: Typhoid vaccine The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution Other Name: Typhim ViĀ® Dietary Supplement: Concentrate beetroot Juice 140 ml which is nitrate-depleted |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Typhoid vaccine | Biological | The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution |
|
| Measure | Description | Time Frame |
|---|---|---|
| Flow mediated dilatation | Comparison of change in FMD from baseline after typhoid vaccination following inorganic nitrate versus placebo supplementation | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) |
| Plasma nitrite concentration | Comparison of change in plasma nitrite concentration following inorganic nitrate versus placebo supplementation | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) |
| Measure | Description | Time Frame |
|---|---|---|
| Markers of acute inflammation | Comparison of change in peripheral markers of inflammation and leucocyte count following nitrate versus placebo supplementation | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) |
| Pulse wave velocity |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amrita Ahluwalia, BSc PhD | William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| William Harvey Research Institute, Barts and The London School of Medicine | London | EC1M 6BQ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10961963 | Background | Hingorani AD, Cross J, Kharbanda RK, Mullen MJ, Bhagat K, Taylor M, Donald AE, Palacios M, Griffin GE, Deanfield JE, MacAllister RJ, Vallance P. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation. 2000 Aug 29;102(9):994-9. doi: 10.1161/01.cir.102.9.994. | |
| 12045164 | Background |
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D014436 | Typhoid-Paratyphoid Vaccines |
| C057664 | Vi polysaccharide vaccine, typhoid |
| ID | Term |
|---|---|
| D022562 | Salmonella Vaccines |
| D001428 | Bacterial Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
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|
| Concentrate beetroot Juice | Dietary Supplement | 140 ml containing ~8 mmol of inorganic nitrate |
|
| Concentrate beetroot Juice (Placebo) | Dietary Supplement | 140 ml which is nitrate-depleted |
|
Comparison of change in PWV from baseline after typhoid vaccination following nitrate versus placebo supplementation |
| Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) |
| Platelet reactivity | Comparison of change in platelet reactivity from baseline after typhoid vaccination following nitrate versus placebo supplementation | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) |
| Plasma nitrate concentration | Comparison of change in plasma nitrate concentration following inorganic nitrate versus placebo supplementation | Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine) |
| Kharbanda RK, Walton B, Allen M, Klein N, Hingorani AD, MacAllister RJ, Vallance P. Prevention of inflammation-induced endothelial dysfunction: a novel vasculo-protective action of aspirin. Circulation. 2002 Jun 4;105(22):2600-4. doi: 10.1161/01.cir.0000017863.52347.6c. |
| 17084260 | Background | Donald AE, Charakida M, Cole TJ, Friberg P, Chowienczyk PJ, Millasseau SC, Deanfield JE, Halcox JP. Non-invasive assessment of endothelial function: which technique? J Am Coll Cardiol. 2006 Nov 7;48(9):1846-50. doi: 10.1016/j.jacc.2006.07.039. Epub 2006 Oct 17. |
| 15364625 | Background | Clapp BR, Hingorani AD, Kharbanda RK, Mohamed-Ali V, Stephens JW, Vallance P, MacAllister RJ. Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc Res. 2004 Oct 1;64(1):172-8. doi: 10.1016/j.cardiores.2004.06.020. |
| 40209616 | Derived | Lau C, Primus CP, Shabbir A, Chhetri I, Ono M, Masucci M, Bin Noorany Aubdool MA, Amarin J, Hamers AJ, Khan Z, Kumar NA, Montalvo Moreira SA, Nuredini G, Osman M, Whitear C, Godec T, Kapil V, Massimo G, Khambata RS, Rathod KS, Ahluwalia A. Accelerating inflammatory resolution in humans to improve endothelial function and vascular health: Targeting the non-canonical pathway for NO. Redox Biol. 2025 May;82:103592. doi: 10.1016/j.redox.2025.103592. Epub 2025 Mar 28. |
| D045424 |
| Complex Mixtures |