Influence of Dietary Nitrate on Vascular Dysfunction and Inflammation

Phase 1

Completed

• Conditions: Cardiovascular Diseases
• Interventions: Biological: Typhoid vaccine; Dietary Supplement: Concentrate beetroot Juice; Dietary Supplement: Concentrate beetroot Juice (Placebo)

• Registration Number: NCT02715635
• Lead Sponsor: Queen Mary University of London

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.

Study Timeline

• Study First Submitted: 2016-03-16
• Study First Submitted QC: 2016-03-16
• Study First Posted: 2016-03-22
• Study Start: 2016-04
• Primary Completion: 2020-12
• Study Completion: 2021-08-01
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-19
• Last Update Posted: 2022-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 78

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nitrate-deplete beetroot juice	Typhoid vaccine	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 Vi® Dietary Supplement: Concentrate beetroot Juice 140 ml which is nitrate-depleted
Nitrate-rich beetroot juice	Typhoid vaccine	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 Vi® Dietary Supplement: Concentrate beetroot Juice 140 ml containing \~8 mmol of inorganic nitrate
Nitrate-rich beetroot juice	Concentrate beetroot Juice	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 Vi® Dietary Supplement: Concentrate beetroot Juice 140 ml containing \~8 mmol of inorganic nitrate
Nitrate-deplete beetroot juice	Concentrate beetroot Juice (Placebo)	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 Vi® Dietary Supplement: Concentrate beetroot Juice 140 ml which is nitrate-depleted

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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

Trial Locations

Locations (1)

William Harvey Research Institute, Barts and The London School of Medicine; 🇬🇧 London, United Kingdom