Influence of Dietary Nitrate on Vascular Dysfunction and Inflammation

Queen Mary University of London

Status and phase: Completed; Phase 1

Conditions: Cardiovascular Diseases

Treatments: Dietary Supplement: Concentrate beetroot Juice; Biological: Typhoid vaccine; Dietary Supplement: Concentrate beetroot Juice (Placebo)

Study type: Interventional

Funder types: Other

Identifiers

NCT02715635

15/LO/0789

Details and patient eligibility

About

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

Full 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.

Enrollment: 78 patients

Sex: Male

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

78 participants in 2 patient groups, including a placebo group

Nitrate-rich beetroot juice

Active Comparator group

Description:

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

Treatment:

Dietary Supplement: Concentrate beetroot Juice

Biological: Typhoid vaccine

Nitrate-deplete beetroot juice

Placebo Comparator group

Description:

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

Treatment:

Biological: Typhoid vaccine

Dietary Supplement: Concentrate beetroot Juice (Placebo)