Investigation of the Effect of Dietary Nitrate Treatment on Endothelial Function and Platelet Reactivity in Hypercholesterolemics.

NCT01493752 | Completed Phase 1

• 1 other identifier: 11/LO/0715
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Diets rich in fruit and vegetables reduce the risk of strokes and heart attacks, however the exact cause of this beneficial effect is uncertain. Evidence suggests that certain vegetables, including beetroot and the green leafy vegetables, possess high inorganic nitrate concentrations. The investigators recent evidence suggests that inorganic nitrate provides a source of gas called nitric oxide in the body that exerts a number of beneficial effects upon the heart and blood vessels . The investigators have previously shown that beetroot juice ingestion improves blood vessel (vascular endothelial) and platelet function in healthy volunteers. Studies by the investigators show that these effects are due to conversion of nitrate to nitrite by symbiotic (helpful) bacteria (located on the tongue) and subsequent conversion of nitrite to nitric oxide in blood vessels. The investigators now wish to explore whether dietary nitrate, via its beneficial effects on platelets and blood vessels, might improve indices of atherosclerotic disease progression in high risk individuals (hypercholesterolemics). Recruits will have high cholesterol and no known atherosclerosis and will not yet be on any anti-cholesterol medications. Volunteers will consume a daily dose of beetroot juice or placebo nitrate-free juice for six weeks. Vascular function will be assessed using non-invasive techniques at the beginning and at the end of the study using ultrasound measurement of flow mediated dilatation (FMD) of the brachial artery in the arm and pulse wave analysis (PWA) and pulse wave velocity (PWV) to measure arterial compliance. To assess impact on platelet function, blood samples will also be taken at the start and at the end of the study.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Flow Mediated Dilatation (FMD)

  Brachial artery ultrasound FMD as a measure of endothelial function before and after beetroot juice

  6 weeks

Secondary Outcomes (1)

• Platelet aggregation studies, pulse wave analysis, pulse wave velocity, plasma nitrate and nitrate concentration.

  after 6 weeks

Study Arms (2)

Nitrate-rich beetroot juice

ACTIVE COMPARATOR

Six weeks once daily dose of nitrate rich beetroot juice

Dietary Supplement: beetroot juice

Nitrate deplete beetroot juice

PLACEBO COMPARATOR

six weeks daily dose beetroot juice (nitrate deplete)

Dietary Supplement: beetroot juice

Interventions

beetroot juice DIETARY_SUPPLEMENT

250mls daily beetroot juice

Nitrate deplete beetroot juice; Nitrate-rich beetroot juice

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants will be between 18-80 years of age.
• They will be largely newly diagnosed patients with hypercholesterolemia (total serum cholesterol\>6.0mmol/L or any elevation of total cholesterol, LDL cholesterol or triglycerides with a QRISK 2 score \>15%).
• We will include patients with familial hypercholesterolemia. These patients in general will either be managed in primary care alone or will attend the clinic following referral from general practitioners for further investigation following routine health tests.
• In addition, patients who have been referred due to inability to tolerate statin treatment will be included.

You may not qualify if:

• Hypercholesterolemics will be screened by taking a medical history and physical examination, blood pressure measurement and urine sample taken to check for diabetes. The subject will continue his/her usual diet and exercise regime prior to diagnosis of hypercholesterolemia for purposes of this study. They will not be taking any additional vitamin or food supplements for the duration of the study.
• A history of symptomatic ischemic heart disease (angina, previous myocardial infarction, acute coronary syndrome) or other known atherosclerosis.
• A history of heart failure NYHA class 2-4 or severe LV dysfunction LVEF\<30% regardless of symptom status.
• Use of statins within 2 months of screening visit.
• A history of diabetes.
• Systemic autoimmune disease such as rheumatoid arthritis, connective tissue disease, or other conditions known to be associated with chronic inflammation such as inflammatory bowel disease.
• Any use of non steroidal anti-Inflammatory drugs, antiplatelet agents or steroids within two months of commencing study or likely future use required during the study.
• Subjects with any acute infection, or significant trauma (burns, fractures).
• Subjects who have donated \> 500mls blood within 56 days prior to study medication administration.
• Anaemia with Hb \<10g/dl, or any other known blood disorder or significant illness that may affect platelet function, and coagulation. Known essential hypertension on antihypertensive medication is not a contraindication.
• History of malignancy within the past 5 years other than non-melanoma skin cancer.
• Any current life threatening condition including severe chronic obstructive airways disease, HIV infection, life threatening arrhythmia that may prevent subject completing the study.
• Alcohol/drug abuse within the past 6 months of screening visit.
• Excess alcohol consumption as defined as regular weekly consumption of \>28 units male and \>21 units female. (Department of Health Guidelines)
• Use of an investigational device or investigational drug within 30 days or 5 half lives (whichever is longer) preceding the first dose of study medication.

Sponsors & Collaborators

• Queen Mary University of London: lead
• British Heart Foundation: collaborator

Study Sites (1)

Barts & The London Medical School, William Harvey Research Institute

London, EC1M 6BQ, United Kingdom

Location

Related Publications (1)

• Velmurugan S, Gan JM, Rathod KS, Khambata RS, Ghosh SM, Hartley A, Van Eijl S, Sagi-Kiss V, Chowdhury TA, Curtis M, Kuhnle GG, Wade WG, Ahluwalia A. Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study. Am J Clin Nutr. 2016 Jan;103(1):25-38. doi: 10.3945/ajcn.115.116244. Epub 2015 Nov 25.

  PMID: 26607938 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Vascular Pharmacology

Study Record Dates

• First Submitted: December 15, 2011
• First Posted: December 16, 2011
• Study Start: August 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: April 9, 2014

Record last verified: 2014-04

Locations

GB (1)