Clinical trial NCT03478631: Dietary Nitrate on Blood Pressure and Cardiovascular Disease Risk Factors
Official title: The Role of Dietary Nitrate on Blood Pressure and Cardiovascular Disease Risk Factors: a Randomized, Controlled Trial in Individuals With Elevated Blood Pressure
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hypertension
Blood Pressure, High
Keywords: nitrate
vegetables
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2018-03-27
Enrollment: 90
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will be a randomized, double-blind, controlled parallel study. There will be two experimental arms of 16-week duration, in which participants are assigned to test or control arms under free living conditions in an outpatient setting.
Primary purpose: TREATMENT

Brief summary: The project aims to determine the effect of a high-nitrate dietary intervention on blood pressure and markers of vascular function compared to a low-nitrate intervention in people with elevated blood pressure. Half of the participants will receive the high-nitrate dehydrated vegetable intervention, while the other half will receive the low-nitrate dehydrated vegetable intervention.This project will advance the current hypothesis on the therapeutic link between dietary nitrate and high blood pressure, and potentially derive impactful recommendations for individuals at risk of hypertension.

Detailed description: Diets rich in fruits and in particular, vegetables, reduce blood pressure (BP) and the risk of cardiovascular events. Increasingly, attention is being given to high-nitrate containing vegetables, with emerging evidence that it might represent a source of vasoactive nitric oxide. Clinical data to date uniformly suggest an acute vasoprotective role of dietary nitrate administration and a BP-lowering effect. Whether the vascular effects extend to long-term intake and in individuals with elevated blood pressure is not well known. The investigators hypothesize that consumption of a dietary intervention high in nitrate from vegetable sources will have a greater effect on BP and related vascular parameters than a similar intervention that is low in dietary nitrates.

Eligibility criteria: Inclusion Criteria:

* BMI 18.5-35 kg/m2
* Seated systolic blood pressure ≥130 and \<160 mmHg

Exclusion Criteria:

* current use of antihypertensive agents
* history of major cardiovascular events in the last 1 year (stroke or myocardial infarction)
* stage II hypertension as per JNC7 criteria (systolic BP/ diastolic BP ≥160/100 mmHg) - angina pectoris
* gastrointestinal (i.e. inflammatory bowel disease, celiac), liver or kidney disease
* cardiac condition that compromises normal function (e.g. mitral valve disease, heart failure)
* serum triglyceride \>4.5mmol/L
* major disability or disorder requiring continuous medical attention
* planned initiation in antihypertensive therapy
* herb or supplement use that may affect primary outcome
* consuming \>3 servings of vegetables/day (based on semi-quantitative food frequency questionnaire)
* alcohol use \>2 drinks/day
* chronic or prescribed use of medications including prescription NSAIDs, antacids, warfarin, medications affecting NO synthesis (ie. sildenafil, organic nitrates, etc)
* use of antibiotics within 3-months of the study start
* participants should also be willing to refrain from using mouthwash (ie chlorhexidine) for the duration of their participation in the study

Primary outcomes:
measure: Systolic Blood Pressure
timeFrame: Baseline, 8 and16 weeks
Secondary outcomes:
measure: Mean 24h and Daytime Ambulatory Systolic, Diastolic and Mean Arterial Blood Pressure
timeFrame: Baseline and 16 weeks
measure: Aortic Systolic and Diastolic Blood Pressure
timeFrame: Baseline, 8 and 16 weeks
measure: Pulse Wave Velocity (PWV)
timeFrame: Baseline and 16 weeks
measure: Augmentation Index (AI)
timeFrame: Baseline, 8 and 16 weeks
measure: High Sensitivity C-reactive protein (hs-CRP)
timeFrame: Baseline and 16 weeks
measure: Plasma Lipids
timeFrame: Baseline and 16 weeks
Other outcomes:
measure: Symptoms Diary
timeFrame: Screening, baseline, 8 and 16 weeks
measure: Aspartate Aminotransferase (AST)
timeFrame: Screening, baseline, 8 and 16 weeks
measure: Creatinine
timeFrame: Screening, baseline, 8 and 16 weeks
measure: Sachet Count
timeFrame: 8 and 16 weeks
measure: 7-Day Food Record
timeFrame: Baseline, 8 and 16 weeks
measure: Nitrate Food Frequency Questionnaire
timeFrame: Biweekly (screening, 0,2,4,6,8,10,12,14,16,18 weeks)
measure: Habitual Physical Activity Questionnaire
timeFrame: Baseline, Week 16
measure: Body Weight
timeFrame: Screening, baseline, 8 and 16 weeks
measure: 24h Urinary Nitrite and Nitrate levels (exploratory outcome, TBD)
timeFrame: 16 weeks
measure: 24h Urinary Potassium levels (exploratory outcome, TBD)
timeFrame: 16 weeks
measure: 24h Urinary Sodium levels (exploratory outcome, TBD)
timeFrame: 16 weeks
measure: Cyclic guanosine monophosphate (cGMP) (exploratory outcome, TBD)
timeFrame: Baseline and 16 weeks
measure: Plasma nitrate/nitrite (exploratory outcome, TBD)
timeFrame: Baseline and 16 weeks
Locations:
city: Toronto
country: Canada
facility: Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
state: Ontario
Study officials:
affiliation: Unity Health Toronto
name: Vladimir Vuksan, PhD
role: PRINCIPAL_INVESTIGATOR
References: