Influence of Dietary Nitrate on Vascular Dysfunction and Inflammation

Cardiovascular Diseases Clinical Trial

Official title:

A Double-blind, Randomised, Placebo-controlled Parallel Study to Investigate the Effect of Dietary Nitrate on a Model of Vascular Dysfunction in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02715635
• Other study ID #: 15/LO/0789
• Status: Completed
• Phase: Phase 1
• Start date: April 2016
• Est. completion date: August 1, 2021

Study information

• Verified date: July 2022
• Source: Queen Mary University of London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: August 1, 2021
• Est. primary completion date: December 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

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

Dietary Supplement:
• Concentrate beetroot Juice
140 ml containing ~8 mmol of inorganic nitrate
• Concentrate beetroot Juice (Placebo)
140 ml which is nitrate-depleted

Locations

Country	Name	City	State
United Kingdom	William Harvey Research Institute, Barts and The London School of Medicine	London

Sponsors (1)

Lead Sponsor	Collaborator
Queen Mary University of London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (4)

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. — View Citation

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. Epub 2006 Oct 17. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	Pulse wave velocity	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)
Secondary	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)
Secondary	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)