AgingNCT01395277
Role of Flavanols In Cardiovascular Function in Healthy Aging
A study testing High Flavanol first then Low Flavanol and Low Flavanol first then High Flavanol in people with Aging, run by University of Texas at Austin at 1 site in United States.
Trial summary
Groups of naturally occurring compounds called flavonoids are found in foods such as fruits and vegetables, red wine, tea, dark chocolate and cocoa products. Diets rich in flavonoids are associated with decreased risk for cardiovascular disease and major cardiovascular events (i.e. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- High Flavanol first then Low Flavanol and Low Flavanol first then High Flavanol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to May 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and Females between 18 - 26 years old
- Males and Females between 65 - 80 years old
Who cannot join
- cardiovascular disease
- metabolic disease
- neurological disease
- Pregnant lady
- Current smoker (or regularly smoked within last year)
- Currently taking medications known to effect the autonomic nervous system
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas at Austin: Environmental and Autonomic Physiolgy Laboratory
Austin, Texas, 78712
About this study
Official title: Effects of Dietary Flavanols on Cutaneous, Peripheral, and Cerebral Vascular Function in Young and Old Humans
Groups of naturally occurring compounds called flavonoids are found in foods such as fruits and vegetables, red wine, tea, dark chocolate and cocoa products. Diets rich in flavonoids are associated with decreased risk for cardiovascular disease and major cardiovascular events (i.e. myocardial infarction) and have been shown to improve blood pressure, insulin sensitivity, and vascular function in a variety populations (Type II diabetes, elderly, smokers, etc.). The presumed beneficial effects of these compounds are thought to act through their inherent ability to scavenge free radicals. Specifically flavonoids scavenge superoxide anions which are free radicals that react with nitric oxide (NO) to produce peroxynitrite. The formation of peroxynitrite ultimately reduces the bioavailability of NO which is essential for vasodilation and thus vascular health and function. Normal aging is associated with impaired endothelial function, which presumably is due to less than optimal levels of NO bioavailability. Therefore, interventions that can increase NO bioavailability would be expected to improve microvascular function and vascular health in this population. The purpose of this study is to investigate the effects of dietary flavonoid supplementation on the vasodilatory capacity of the cutaneous vasculature, as well as on cerebral vascular reactivity and arterial stiffness in young and old humans. This study will test the hypothesis that acute dietary flavonoid treatment will improve impaired cutaneous vasodilatory capacity, cerebral vasomotor reactivity, and reduce arterial stiffness in older but not young humans.
Read the detailed description
Role of nitric oxide in vascular function. Nitric oxide (NO) is an important signaling molecule involved in many physiological processes. Of particular interest is its role in endothelial function and blood flow regulation. In response to heat or sheer stress against the walls of blood vessels, the endothelial layer of blood vessels releases NO, which causes smooth muscle in the vessel wall to relax and the vessel to dilate. Environmental heat-stress leads to an increase in skin blood flow to allow for improved heat loss from the body surface to the environment, and relies on NO. Normal aging reduces NO bioavailability leading to an impaired ability to increase skin blood flow in response to environmental heat-stress. Additionally, cerebral blood flow is reduced and arterial stiffness is increased in the normal aging process which is at least partially attributed to reductions in NO bioavailability.
Effects of dietary flavonoids. As previously mentioned Flavonoids are a group of natural compounds found in vegetables, fruits, wine, tea, and cocoa. Flavanols are a subfamily of flavonoids, and are quantitatively the most important compound in flavonoid family in western diets. Flavanol intake has been shown to improve vascular health, as well as increase insulin sensitivity, decrease blood pressure, reduce platelet aggregation, and enhance cerebral blood flow. The basic chemical features of flavanol allows them to act as classic antioxidants to scavenge free-radicals decreasing oxidant level in cells. High levels of free radicals, especially superoxide, can reduce the bioavailability of NO and thus any NO-mediated actions. Cocoa and cocoa products are potent sources of flavanols, and therefore have been used extensively as a dietary intervention to study the effects of flavanol supplementation on various disease states.
Impairments in vascular health in the normal aging process. The ability to increase skin blood flow in response to environmental heat-stress is lost with normal aging, especially when individuals exceed 65 years of age. An attenuated skin blood flow response during exposure to environmental heat stress would place these older individuals at an increased risk for heat-related illness or death. The ability to raise skin blood flow with rising skin temperature has been demonstrated to have a large nitric oxide component, so a deficit in NO bioavailability, which is also consistently observed in aging populations, could presumably lead to the attenuated skin blood flow response to heat stress. Furthermore, it is well documented that cerebral blood flow is reduced while arterial stiffness is increased in the normal aging process. In regard to the reduction in NO in aging populations, flavanol supplementation has been shown to decrease production of free radicals, which can scavenge and reduce NO levels thereby improving indices of vascular health including flow mediated vasodilation. Therefore, flavanol supplementation may maintain NO bioavailability at optimal levels, and provide a feasible way for aging populations to maintain vascular health and prevent heat-related illness and death.
Significance:
This study will address the mechanisms of impaired cutaneous and cerebral blood flow as well as increased arterial stiffness that can occur in aging populations. Furthermore, if the hypothesis is correct, findings from this study will provide evidence for the efficacy of flavanols to be used (as a simple and safe lifestyle intervention) to reverse or combat impaired vascular function that commonly occurs in older individuals.
- Conditions
- Aging
- Being tested
- High Flavanol first then Low Flavanol, Low Flavanol first then High Flavanol
- Keywords
- Nitric Oxide, Vascular Function, Aging, Blood Pressure, Arterial Stiffness, Cardiovascular Disease, Cerebral Blood Flow
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Flavanol first then Low FlavanolDietary supplement
Also called dark chocolate beverage
The high flavanol trial will be performed following consumption of a beverage containing 1,050 mg of commercially available Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. The low flavanol trial will be performed following consumption of a beverage containing 0 mg of Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption.
Low Flavanol first then High FlavanolDietary supplement
Also called chocolate, Mars Incorporated
The low flavanol trial will be performed following consumption of a beverage containing 0 mg of Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. The high flavanol trial will be performed following consumption of a beverage containing 1,050 mg of commercially available Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption.
| Study group | Role | What they receive |
|---|---|---|
| High Flavanol first then Low Flavanol | Experimental | The measurements will be made on all study participants on two separate occasions; 1) before and 2 hours following consumption of a beverage with "high" flavanol content and 2) before and 2 hours following consumption of a beverage with "low" flavanol content. Receives: Dietary Supplement: High Flavanol first then Low Flavanol |
| Low Flavanol first then High Flavanol | Experimental | The measurements will be made on all study participants on two separate occasions; 1) before and 2 hours following consumption of a beverage with "low" flavanol content and 2) before and 2 hours following consumption of a beverage with "high" flavanol content. Receives: Dietary Supplement: Low Flavanol first then High Flavanol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cutaneous Blood Flow Response to Local Heating of the Skin.
Local heating of the cutaneous vasculature to 42 degree C is commonly used to evoke a maximal skin blood flow response (only at the site of local heating). This response is almost entirely dependent on nitric oxide mediated vasodilation.
Measured: prior to (baseline) and 2 hours post beverage consumption
Secondary outcomes (1)
Pulse Wave Velocity / Arterial Stiffness
Assessment of pulse wave velocity in the common carotid artery and the femoral artery provides an index of arterial stiffness.
Measured: Prior to (baseline) and 2 hours following beverage consumption
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2011 (estimated)
- Study startSep 2011
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by University of Texas at AustinThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas at Austin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert M. Brothers, University of Texas at Austin
- Investigators
- R. Matthew Brothers, PhD, Principal investigator, University of Texas at Austin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01395277
- Sponsor's protocol ID
- 2011-05-0029
- Status last verified
- Jul 2015
- First submitted
- 13 Jul 2011
- Last updated
- 10 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Dietary Flavanols on Cutaneous, Peripheral, and Cerebral Vascular Function in Young and Old Humans
- ClinicalTrials.gov ID
- NCT01395277
- Acronym / sponsor ID
- 2011-05-0029
- Conditions
- Aging
- Keywords
- Nitric Oxide, Vascular Function, Aging, Blood Pressure, Arterial Stiffness, Cardiovascular Disease, Cerebral Blood Flow
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of Texas at AustinUniversity, hospital or other
- Study start
- Sep 2011
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 15 Jul 2011 (estimated)
- Results
- Posted 10 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Groups of naturally occurring compounds called flavonoids are found in foods such as fruits and vegetables, red wine, tea, dark chocolate and cocoa products. Diets rich in flavonoids are associated with decreased risk for cardiovascular disease and major cardiovascular events (i.e. myocardial infarction) and have been shown to improve blood pressure, insulin sensitivity, and vascular function in a variety populations (Type II diabetes, elderly, smokers, etc.). The presumed beneficial effects of these compounds are thought to act through their inherent ability to scavenge free radicals. Specifically flavonoids scavenge superoxide anions which are free radicals that react with nitric oxide (NO) to produce peroxynitrite. The formation of peroxynitrite ultimately reduces the bioavailability of NO which is essential for vasodilation and thus vascular health and function. Normal aging is associated with impaired endothelial function, which presumably is due to less than optimal levels of NO bioavailability. Therefore, interventions that can increase NO bioavailability would be expected to improve microvascular function and vascular health in this population. The purpose of this study is to investigate the effects of dietary flavonoid supplementation on the vasodilatory capacity of the cutaneous vasculature, as well as on cerebral vascular reactivity and arterial stiffness in young and old humans. This study will test the hypothesis that acute dietary flavonoid treatment will improve impaired cutaneous vasodilatory capacity, cerebral vasomotor reactivity, and reduce arterial stiffness in older but not young humans.
Detailed description
Role of nitric oxide in vascular function. Nitric oxide (NO) is an important signaling molecule involved in many physiological processes. Of particular interest is its role in endothelial function and blood flow regulation. In response to heat or sheer stress against the walls of blood vessels, the endothelial layer of blood vessels releases NO, which causes smooth muscle in the vessel wall to relax and the vessel to dilate. Environmental heat-stress leads to an increase in skin blood flow to allow for improved heat loss from the body surface to the environment, and relies on NO. Normal aging reduces NO bioavailability leading to an impaired ability to increase skin blood flow in response to environmental heat-stress. Additionally, cerebral blood flow is reduced and arterial stiffness is increased in the normal aging process which is at least partially attributed to reductions in NO bioavailability.
Effects of dietary flavonoids. As previously mentioned Flavonoids are a group of natural compounds found in vegetables, fruits, wine, tea, and cocoa. Flavanols are a subfamily of flavonoids, and are quantitatively the most important compound in flavonoid family in western diets. Flavanol intake has been shown to improve vascular health, as well as increase insulin sensitivity, decrease blood pressure, reduce platelet aggregation, and enhance cerebral blood flow. The basic chemical features of flavanol allows them to act as classic antioxidants to scavenge free-radicals decreasing oxidant level in cells. High levels of free radicals, especially superoxide, can reduce the bioavailability of NO and thus any NO-mediated actions. Cocoa and cocoa products are potent sources of flavanols, and therefore have been used extensively as a dietary intervention to study the effects of flavanol supplementation on various disease states.
Impairments in vascular health in the normal aging process. The ability to increase skin blood flow in response to environmental heat-stress is lost with normal aging, especially when individuals exceed 65 years of age. An attenuated skin blood flow response during exposure to environmental heat stress would place these older individuals at an increased risk for heat-related illness or death. The ability to raise skin blood flow with rising skin temperature has been demonstrated to have a large nitric oxide component, so a deficit in NO bioavailability, which is also consistently observed in aging populations, could presumably lead to the attenuated skin blood flow response to heat stress. Furthermore, it is well documented that cerebral blood flow is reduced while arterial stiffness is increased in the normal aging process. In regard to the reduction in NO in aging populations, flavanol supplementation has been shown to decrease production of free radicals, which can scavenge and reduce NO levels thereby improving indices of vascular health including flow mediated vasodilation. Therefore, flavanol supplementation may maintain NO bioavailability at optimal levels, and provide a feasible way for aging populations to maintain vascular health and prevent heat-related illness and death.
Significance:
This study will address the mechanisms of impaired cutaneous and cerebral blood flow as well as increased arterial stiffness that can occur in aging populations. Furthermore, if the hypothesis is correct, findings from this study will provide evidence for the efficacy of flavanols to be used (as a simple and safe lifestyle intervention) to reverse or combat impaired vascular function that commonly occurs in older individuals.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Flavanol first then Low Flavanol | Experimental | Dietary Supplement: High Flavanol first then Low FlavanolThe measurements will be made on all study participants on two separate occasions; 1) before and 2 hours following consumption of a beverage with "high" flavanol content and 2) before and 2 hours following consumption of a beverage with "low" flavanol content. |
| Low Flavanol first then High Flavanol | Experimental | Dietary Supplement: Low Flavanol first then High FlavanolThe measurements will be made on all study participants on two separate occasions; 1) before and 2 hours following consumption of a beverage with "low" flavanol content and 2) before and 2 hours following consumption of a beverage with "high" flavanol content. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Males and Females between 18 - 26 years old
- Males and Females between 65 - 80 years old
Key exclusion criteria (6 listed)
- cardiovascular disease
- metabolic disease
- neurological disease
- Pregnant lady
- Current smoker (or regularly smoked within last year)
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 |
|---|---|---|
| High Flavanol first then Low FlavanolAlso: dark chocolate beverageThe high flavanol trial will be performed following consumption of a beverage containing 1,050 mg of commercially available Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. The low flavanol trial will be performed following consumption of a beverage containing 0 mg of Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. | Dietary supplement | High Flavanol first then Low Flavanol |
| Low Flavanol first then High FlavanolAlso: chocolate, Mars IncorporatedThe low flavanol trial will be performed following consumption of a beverage containing 0 mg of Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. The high flavanol trial will be performed following consumption of a beverage containing 1,050 mg of commercially available Cocoa Flavanols which will be mixed into 250 ml of distilled water. The subjects will consume this beverage and measurements will be performed 2 hours after consumption. | Dietary supplement | Low Flavanol first then High Flavanol |
Primary outcome
Cutaneous Blood Flow Response to Local Heating of the Skin.
Time frame: prior to (baseline) and 2 hours post beverage consumption
Local heating of the cutaneous vasculature to 42 degree C is commonly used to evoke a maximal skin blood flow response (only at the site of local heating). This response is almost entirely dependent on nitric oxide mediated vasodilation.
1 secondary outcome
Pulse Wave Velocity / Arterial Stiffness
Time frame: Prior to (baseline) and 2 hours following beverage consumption
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
R. Matthew Brothers, PhD principal investigator
University of Texas at Austin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High Flavanol first then Low Flavanol and Low Flavanol first then High Flavanol in people with Aging, run by University of Texas at Austin at 1 site in United States.
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 2 inclusion and 6 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 10 Aug 2015. 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 States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cutaneous Blood Flow Response to Local Heating of the Skin. (time frame: prior to (baseline) and 2 hours post beverage consumption). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Aug 2015.