Dietary Nitrate on Blood Pressure and Cardiovascular Disease Risk Factors

The Role of Dietary Nitrate on Blood Pressure and Cardiovascular Disease Risk Factors: a Randomized, Controlled Trial in Individuals With Elevated Blood Pressure

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.

Study Overview

• Status: Unknown
• Conditions: Hypertension; Blood Pressure, High
• Intervention / Treatment: Other: High-nitrate dehydrated vegetable powder; Other: Low-nitrate dehydrated vegetable powder

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.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Elena Jovanovski, MSc; Phone Number: 2597 416 864 6060; Email: JovanovskiE@smh.ca
• Study Contact Backup: Name: Dandan Li, MSc (c); Phone Number: 5527 416 864 6060; Email: LiDand@smh.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
      • Contact: Elena Jovanovski, MSc; Phone Number: 2597 416-864-6060; Email: JovanovskiE@smh.ca
      • Contact: Dandan Li, MSc (c); Phone Number: 5527 416-864-6060; Email: LiDand@smh.ca
      • Principal Investigator: Vladimir Vuksan, PhD
      • Sub-Investigator: John Sievenpiper (Qualified Investigator), MD, PhD
      • Sub-Investigator: Verma Subodh, MD,FRCSC,PhD
      • Sub-Investigator: David Jenkins, MD, PhD, DSc
      • Sub-Investigator: Alexandra Jenkins, PhD, RD
      • Sub-Investigator: Elena Jovanovski, MSc, PhD (c)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High Nitrate Dehydrated Vegetables; Participants are given high-nitrate dehydrated vegetable powders contained in opaque sachets. Participants are advised to consume three sachets per day, over the course of three meals, for 16 weeks.	Other: High-nitrate dehydrated vegetable powder; A mixed combination of vegetable powders that are naturally high in nitrate content, such as beet, spinach, and kale
ACTIVE_COMPARATOR: Low-Nitrate Dehydrated Vegetables; Participants are given low-nitrate dehydrated vegetable powders contained in three opaque sachets. Participants are advised to consume three sachets per day, over the course of three meals, for 16 weeks.	Other: Low-nitrate dehydrated vegetable powder; A mixed combination of vegetable powders that are naturally low in nitrate content, such as peas, tomato, broccoli, carrots, and brussel sprouts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure	Change in systolic blood pressure vs. control at 16 weeks	Baseline, 8 and16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 24h and Daytime Ambulatory Systolic, Diastolic and Mean Arterial Blood Pressure	Change in mean 24h and daytime ambulatory systolic, diastolic and mean arterial blood pressure vs. control at 16 weeks	Baseline and 16 weeks
Aortic Systolic and Diastolic Blood Pressure	Change in aortic systolic and diastolic blood pressure vs. control at 16 weeks	Baseline, 8 and 16 weeks
Pulse Wave Velocity (PWV)	Change in PWV vs. control at 16 weeks	Baseline and 16 weeks
Augmentation Index (AI)	Change in AI vs. control at 16 weeks	Baseline, 8 and 16 weeks
High Sensitivity C-reactive protein (hs-CRP)	Change in hs-CRP vs. control at 16 weeks	Baseline and 16 weeks
Plasma Lipids	Change in Total-C, LDL-C, HDL-C vs. control at 16 weeks	Baseline and 16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptoms Diary	Record of any adverse symptoms experienced and the level of severity	Screening, baseline, 8 and 16 weeks
Aspartate Aminotransferase (AST)	Liver function test	Screening, baseline, 8 and 16 weeks
Creatinine	Kidney function test	Screening, baseline, 8 and 16 weeks
Sachet Count	Record of the amount of sachets and contents returned	8 and 16 weeks
7-Day Food Record	Record of food intake 7 days prior to study visit day	Baseline, 8 and 16 weeks
Nitrate Food Frequency Questionnaire	Assess consumption of nitrate-rich meats and vegetables	Biweekly (screening, 0,2,4,6,8,10,12,14,16,18 weeks)
Habitual Physical Activity Questionnaire	Questions to assess level of physical activity	Baseline, Week 16
Body Weight	Body Weight in kg	Screening, baseline, 8 and 16 weeks
24h Urinary Nitrite and Nitrate levels (exploratory outcome, TBD)	Marker of treatment compliance	16 weeks
24h Urinary Potassium levels (exploratory outcome, TBD)	Urine samples collected for estimation of potassium intake	16 weeks
24h Urinary Sodium levels (exploratory outcome, TBD)	Urine samples collected for estimation of sodium intake	16 weeks
Cyclic guanosine monophosphate (cGMP) (exploratory outcome, TBD)	Change in cGMP vs. control at 16 weeks	Baseline and 16 weeks
Plasma nitrate/nitrite (exploratory outcome, TBD)	Change in plasma nitrate and nitrite vs. control at 16 weeks	Baseline and 16 weeks

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR)

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 1, 2018
• Primary Completion (ANTICIPATED): August 1, 2020
• Study Completion (ANTICIPATED): August 1, 2020

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (ACTUAL): March 27, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: vegetables; nitrate
• Additional Relevant MeSH Terms: Vascular Diseases; Hypertension; Cardiovascular Diseases
• Other Study ID Numbers: DINO3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No