HypercholesterolemiaPhase 1NCT01493752
Investigation of the Effect of Dietary Nitrate Treatment on Endothelial Function and Platelet Reactivity in Hypercholesterolemics.
A Phase 1 study testing beetroot juice in people with Hypercholesterolemia, run by Queen Mary University of London at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- beetroot juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2011to May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- They will be recruited into the study if they are interested in taking part in research, do not have any exclusion criteria on screening and give their written informed consent.
- 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.
Who cannot join
- 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.
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- 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.
- Any non stable dosing of ongoing medication regimens throughout the study trial.
- A history of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody or other chronic hepatic disorder.)
- Abnormal liver function due to acute or chronic liver conditions 3 x upper limit of normal at screening.
- Renal impairment with creatinine clearance (eGFR) of <50ml/min at screening.
- Pregnancy at time of screening or intention of getting pregnant during course of study.
- Current smokers or ex smokers who stopped smoking <3 months prior to administration of study medication.
- BMI <18.5 or > or = 40kg/m2.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Barts & The London Medical School, William Harvey Research Institute
London, EC1M 6BQ
About this study
Official title: Investigation of the Effect of Dietary Nitrate Treatment on Endothelial Function, Platelet Reactivity in Hypercholesterolemics Without Known Cardiovascular Disease or Atherosclerosis.
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.
Read the detailed description
Please refer to brief summary.
- Conditions
- Hypercholesterolemia
- Being tested
- beetroot juice
- Medical subject headings
- Hypercholesterolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
beetroot juiceDietary supplement
250mls daily beetroot juice
| Study group | Role | What they receive |
|---|---|---|
| Nitrate-rich beetroot juice | Active comparator | Six weeks once daily dose of nitrate rich beetroot juice Receives: Dietary Supplement: beetroot juice |
| Nitrate deplete beetroot juice | Placebo comparator | six weeks daily dose beetroot juice (nitrate deplete) Receives: Dietary Supplement: beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Flow Mediated Dilatation (FMD)
Brachial artery ultrasound FMD as a measure of endothelial function before and after beetroot juice
Measured: 6 weeks
Secondary outcomes (1)
Platelet aggregation studies, pulse wave analysis, pulse wave velocity, plasma nitrate and nitrate concentration.
Measured: after 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2011 (estimated)
- Study startAug 2011
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by Queen Mary University of LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation
- Responsible party
- Principal investigator, Amrita Ahluwalia, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01493752
- Sponsor's protocol ID
- 11/LO/0715
- Status last verified
- Apr 2014
- First submitted
- 15 Dec 2011
- Last updated
- 9 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26607938
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Effect of Dietary Nitrate Treatment on Endothelial Function, Platelet Reactivity in Hypercholesterolemics Without Known Cardiovascular Disease or Atherosclerosis.
- ClinicalTrials.gov ID
- NCT01493752
- Acronym / sponsor ID
- 11/LO/0715
- Conditions
- Hypercholesterolemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Collaborators
- British Heart Foundation
- Study start
- Aug 2011
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 16 Dec 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Please refer to brief summary.
Study design
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitrate-rich beetroot juice | Active comparator | Dietary Supplement: beetroot juiceSix weeks once daily dose of nitrate rich beetroot juice |
| Nitrate deplete beetroot juice | Placebo comparator | Dietary Supplement: beetroot juicesix weeks daily dose beetroot juice (nitrate deplete) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- They will be recruited into the study if they are interested in taking part in research, do not have any exclusion criteria on screening and give their written informed consent.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| beetroot juice250mls daily beetroot juice | Dietary supplement | Nitrate deplete beetroot juice, Nitrate-rich beetroot juice |
Primary outcome
Flow Mediated Dilatation (FMD)
Time frame: 6 weeks
Brachial artery ultrasound FMD as a measure of endothelial function before and after beetroot juice
1 secondary outcome
Platelet aggregation studies, pulse wave analysis, pulse wave velocity, plasma nitrate and nitrate concentration.
Time frame: after 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2014.
- Derived from this study: PubMed 26607938Velmurugan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing beetroot juice in people with Hypercholesterolemia, run by Queen Mary University of London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Flow Mediated Dilatation (FMD) (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01493752, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2014.