Clinical trial NCT02715635: Influence of Dietary Nitrate on Vascular Dysfunction and Inflammation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiovascular Diseases
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
First posted: 2016-03-22
Enrollment: 78
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Flow mediated dilatation
timeFrame: Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)
measure: Plasma nitrite concentration
timeFrame: Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)
Secondary outcomes:
measure: Markers of acute inflammation
timeFrame: Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)
measure: Pulse wave velocity
timeFrame: Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)
measure: Platelet reactivity
timeFrame: Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)
measure: Plasma nitrate concentration
timeFrame: Day 1, Day 7 (8 hours post typhoid vaccine), Day 8 (32 hours post typhoid vaccine)
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: William Harvey Research Institute, Barts and The London School of Medicine
Study officials:
affiliation: William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry
name: Amrita Ahluwalia, BSc PhD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1161/01.cir.102.9.994.
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. doi: 10.1161/01.cir.0000017863.52347.6c.
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. doi: 10.1016/j.jacc.2006.07.039. Epub 2006 Oct 17.
citation: 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.