NCT02715635

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P75+ for phase_1 cardiovascular-diseases

Timeline
Completed

Started Apr 2016

Longer than P75 for phase_1 cardiovascular-diseases

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 16, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 22, 2016

Completed
10 days until next milestone

Study Start

First participant enrolled

April 1, 2016

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2021

Completed
Last Updated

July 20, 2022

Status Verified

July 1, 2022

Enrollment Period

4.7 years

First QC Date

March 16, 2016

Last Update Submit

July 19, 2022

Conditions

Cardiovascular Diseases

Outcome Measures

Primary Outcomes (2)

  • 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)

Secondary Outcomes (4)

  • Markers of acute inflammation

    Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)

  • Pulse wave velocity

    Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)

  • Platelet reactivity

    Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)

  • Plasma nitrate concentration

    Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)

Study Arms (2)

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 Vi® Dietary Supplement: Concentrate beetroot Juice 140 ml containing \~8 mmol of inorganic nitrate

Biological: Typhoid vaccineDietary Supplement: Concentrate beetroot Juice

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 Vi® Dietary Supplement: Concentrate beetroot Juice 140 ml which is nitrate-depleted

Biological: Typhoid vaccineDietary Supplement: Concentrate beetroot Juice (Placebo)

Interventions

Typhoid vaccineBIOLOGICAL

The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution

Also known as: Typhim Vi®
Nitrate-deplete beetroot juiceNitrate-rich beetroot juice
Concentrate beetroot JuiceDIETARY_SUPPLEMENT

140 ml containing \~8 mmol of inorganic nitrate

Nitrate-rich beetroot juice
Concentrate beetroot Juice (Placebo)DIETARY_SUPPLEMENT

140 ml which is nitrate-depleted

Nitrate-deplete beetroot juice

Eligibility Criteria

Age18 Years - 45 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Healthy volunteers
  • Aged 18-45
  • Volunteers who are willing to sign the consent form.
  • Normal resting blood pressure (\<140/90 mmHg)

You may not qualify if:

  • Healthy subjects unwilling to consent
  • Pregnant, or any possibility that a subject may be pregnant unless in the latter case a pregnancy test is performed with a negative result
  • 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 (3 months) 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 typhoid vaccination in the last 6 months
  • Subjects with any history of a blood-borne infectious disease such Hepatitis B or C virus, or HIV

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

William Harvey Research Institute, Barts and The London School of Medicine

London, EC1M 6BQ, United Kingdom

Location

Related Publications (5)

  • 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.

    PMID: 10961963BACKGROUND

  • 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.

    PMID: 12045164BACKGROUND

  • 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.

    PMID: 17084260BACKGROUND

  • 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.

    PMID: 15364625BACKGROUND

  • 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.

    PMID: 40209616DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Typhoid-Paratyphoid VaccinesVi polysaccharide vaccine, typhoid

Intervention Hierarchy (Ancestors)

Salmonella VaccinesBacterial VaccinesVaccinesBiological ProductsComplex Mixtures

Study Officials

  • Amrita Ahluwalia, BSc PhD

    William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of The William Harvey Research Institute, Prof of Vascular Pharmacology

Study Record Dates

First Submitted

March 16, 2016

First Posted

March 22, 2016

Study Start

April 1, 2016

Primary Completion

December 1, 2020

Study Completion

August 1, 2021

Last Updated

July 20, 2022

Record last verified: 2022-07

Locations

GB(1)