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Dietary Nitrate on Blood Pressure and Cardiovascular Disease Risk Factors

Primary Purpose

Hypertension, Blood Pressure, High

Status
Unknown status
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
High-nitrate dehydrated vegetable powder
Low-nitrate dehydrated vegetable powder
Sponsored by
Unity Health Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension focused on measuring nitrate, vegetables

Eligibility Criteria

30 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

High Nitrate Dehydrated Vegetables

Low-Nitrate Dehydrated Vegetables

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Systolic Blood Pressure
Change in systolic blood pressure vs. control at 16 weeks

Secondary Outcome Measures

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
Aortic Systolic and Diastolic Blood Pressure
Change in aortic systolic and diastolic blood pressure vs. control at 16 weeks
Pulse Wave Velocity (PWV)
Change in PWV vs. control at 16 weeks
Augmentation Index (AI)
Change in AI vs. control at 16 weeks
High Sensitivity C-reactive protein (hs-CRP)
Change in hs-CRP vs. control at 16 weeks
Plasma Lipids
Change in Total-C, LDL-C, HDL-C vs. control at 16 weeks

Full Information

First Posted
March 20, 2018
Last Updated
March 26, 2018
Sponsor
Unity Health Toronto
Collaborators
Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT03478631
Brief Title
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

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Unknown status
Study Start Date
August 2018 (Anticipated)
Primary Completion Date
August 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Unity Health Toronto
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Blood Pressure, High
Keywords
nitrate, vegetables

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants and study coordinators will be blinded to the nature of the treatment allocation. Stratified randomization lists by baseline sex and age will be created.
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
High Nitrate Dehydrated Vegetables
Arm Type
Experimental
Arm Description
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.
Arm Title
Low-Nitrate Dehydrated Vegetables
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
High-nitrate dehydrated vegetable powder
Intervention Description
A mixed combination of vegetable powders that are naturally high in nitrate content, such as beet, spinach, and kale
Intervention Type
Other
Intervention Name(s)
Low-nitrate dehydrated vegetable powder
Intervention Description
A mixed combination of vegetable powders that are naturally low in nitrate content, such as peas, tomato, broccoli, carrots, and brussel sprouts
Primary Outcome Measure Information:
Title
Systolic Blood Pressure
Description
Change in systolic blood pressure vs. control at 16 weeks
Time Frame
Baseline, 8 and16 weeks
Secondary Outcome Measure Information:
Title
Mean 24h and Daytime Ambulatory Systolic, Diastolic and Mean Arterial Blood Pressure
Description
Change in mean 24h and daytime ambulatory systolic, diastolic and mean arterial blood pressure vs. control at 16 weeks
Time Frame
Baseline and 16 weeks
Title
Aortic Systolic and Diastolic Blood Pressure
Description
Change in aortic systolic and diastolic blood pressure vs. control at 16 weeks
Time Frame
Baseline, 8 and 16 weeks
Title
Pulse Wave Velocity (PWV)
Description
Change in PWV vs. control at 16 weeks
Time Frame
Baseline and 16 weeks
Title
Augmentation Index (AI)
Description
Change in AI vs. control at 16 weeks
Time Frame
Baseline, 8 and 16 weeks
Title
High Sensitivity C-reactive protein (hs-CRP)
Description
Change in hs-CRP vs. control at 16 weeks
Time Frame
Baseline and 16 weeks
Title
Plasma Lipids
Description
Change in Total-C, LDL-C, HDL-C vs. control at 16 weeks
Time Frame
Baseline and 16 weeks
Other Pre-specified Outcome Measures:
Title
Symptoms Diary
Description
Record of any adverse symptoms experienced and the level of severity
Time Frame
Screening, baseline, 8 and 16 weeks
Title
Aspartate Aminotransferase (AST)
Description
Liver function test
Time Frame
Screening, baseline, 8 and 16 weeks
Title
Creatinine
Description
Kidney function test
Time Frame
Screening, baseline, 8 and 16 weeks
Title
Sachet Count
Description
Record of the amount of sachets and contents returned
Time Frame
8 and 16 weeks
Title
7-Day Food Record
Description
Record of food intake 7 days prior to study visit day
Time Frame
Baseline, 8 and 16 weeks
Title
Nitrate Food Frequency Questionnaire
Description
Assess consumption of nitrate-rich meats and vegetables
Time Frame
Biweekly (screening, 0,2,4,6,8,10,12,14,16,18 weeks)
Title
Habitual Physical Activity Questionnaire
Description
Questions to assess level of physical activity
Time Frame
Baseline, Week 16
Title
Body Weight
Description
Body Weight in kg
Time Frame
Screening, baseline, 8 and 16 weeks
Title
24h Urinary Nitrite and Nitrate levels (exploratory outcome, TBD)
Description
Marker of treatment compliance
Time Frame
16 weeks
Title
24h Urinary Potassium levels (exploratory outcome, TBD)
Description
Urine samples collected for estimation of potassium intake
Time Frame
16 weeks
Title
24h Urinary Sodium levels (exploratory outcome, TBD)
Description
Urine samples collected for estimation of sodium intake
Time Frame
16 weeks
Title
Cyclic guanosine monophosphate (cGMP) (exploratory outcome, TBD)
Description
Change in cGMP vs. control at 16 weeks
Time Frame
Baseline and 16 weeks
Title
Plasma nitrate/nitrite (exploratory outcome, TBD)
Description
Change in plasma nitrate and nitrite vs. control at 16 weeks
Time Frame
Baseline and 16 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elena Jovanovski, MSc
Phone
416 864 6060
Ext
2597
Email
JovanovskiE@smh.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Dandan Li, MSc (c)
Phone
416 864 6060
Ext
5527
Email
LiDand@smh.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vladimir Vuksan, PhD
Organizational Affiliation
Unity Health Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elena Jovanovski, MSc
Phone
416-864-6060
Ext
2597
Email
JovanovskiE@smh.ca
First Name & Middle Initial & Last Name & Degree
Dandan Li, MSc (c)
Phone
416-864-6060
Ext
5527
Email
LiDand@smh.ca
First Name & Middle Initial & Last Name & Degree
Vladimir Vuksan, PhD
First Name & Middle Initial & Last Name & Degree
John Sievenpiper (Qualified Investigator), MD, PhD
First Name & Middle Initial & Last Name & Degree
Verma Subodh, MD,FRCSC,PhD
First Name & Middle Initial & Last Name & Degree
David Jenkins, MD, PhD, DSc
First Name & Middle Initial & Last Name & Degree
Alexandra Jenkins, PhD, RD
First Name & Middle Initial & Last Name & Degree
Elena Jovanovski, MSc, PhD (c)

12. IPD Sharing Statement

Plan to Share IPD
No

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Dietary Nitrate on Blood Pressure and Cardiovascular Disease Risk Factors

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