Influence of Dietary Nitrate on Vascular Dysfunction and Inflammation

• Sponsor: Queen Mary University of London (Other)
• Overall Status: Completed
• CT.gov ID: NCT02715635
• Collaborator: (none)
• Enrollment: 78
• Location: 1
• Arms: 2
• Actual Duration (Months): 64
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases	Biological: Typhoid vaccine; Dietary Supplement: Concentrate beetroot Juice; Dietary Supplement: Concentrate beetroot Juice (Placebo)	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Dec 1, 2020
• Actual Study Completion Date: Aug 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Nitrate-rich 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	Biological: Typhoid vaccine; The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution; Other Names: Typhim Vi® ; Dietary Supplement: Concentrate beetroot Juice; 140 ml containing ~8 mmol of inorganic nitrate
Placebo Comparator: Nitrate-deplete 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 which is nitrate-depleted	Biological: Typhoid vaccine; The typhoid vaccine is composed of purified polysaccharide from S. typhi capsule 25 micrograms contained in 0.5 ml solution; Other Names: Typhim Vi® ; Dietary Supplement: Concentrate beetroot Juice (Placebo); 140 ml which is nitrate-depleted

Outcome Measures

Primary Outcome Measures

1. 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

2. 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

1. 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

2. 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

3. 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

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	William Harvey Research Institute, Barts and The London School of Medicine	London		United Kingdom	EC1M 6BQ

Sponsors and Collaborators

• Queen Mary University of London

Investigators

• Principal Investigator: Amrita Ahluwalia, BSc PhD, William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.

• Responsible Party: Amrita Ahluwalia, Director of The William Harvey Research Institute, Prof of Vascular Pharmacology, Queen Mary University of London
• ClinicalTrials.gov Identifier: NCT02715635
• Other Study ID Numbers: 15/LO/0789
• First Posted: Mar 22, 2016
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Additional relevant MeSH terms: Cardiovascular Diseases

Study Results

No Results Posted as of Jul 20, 2022