- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04236388
Short Term Ketone Supplementation and Cardiometabolic Health
Short Term Dietary Ketone Drink Consumption and Cardiometabolic Health in Adults
The purpose of this research study is to determine if short-term consumption of a dietary ketone drink, which increases the blood circulation concentrations of beta-hydroxybutyrate, a ketone, affects blood vessel health and cognitive health in adults. Ketones are normally produced by the liver when people fast longer than 16-24 hours or eat a diet low in carbohydrates. Participants will be asked to randomly consume a dietary ketone drink and placebo (flavored water) for a 2-week period each in a crossover fashion with a 2-week washout period while maintaining habitual diet and physical activity patterns.
The investigators hypothesize that consumption of a ketone drink will reduce BP and improve vascular health by reducing aortic pulse wave velocity and increasing brachial artery flow mediated dilation. Furthermore, they hypothesize that ketone consumption will improve cognitive health by increasing attention and processing speed.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Objective: The objective of this study is threefold: 1) To establish feasibility and proof-of-concept for the efficacy of ketone supplementation in reducing blood pressure and improving vascular and cognitive function in older adults; 2) Establish proficiency and feasibility with the proposed cognitive function measurements; and 3) Obtain preliminary data for effect size generation.
Background: Age is the primary risk factor for cardiovascular disease. Middle age is a vulnerable period where cardiovascular risk factors, such as BP, begin to emerge and signs and symptoms of disease first becomes evident. Hypertension is present in 60-75% of adults in this demographic and associated with vascular dysfunction and cognitive decline. Low Carbohydrate High Fat (LCHF) ketogenic diets have become increasingly popular for improving cardiometabolic health but adherence is suboptimal due to their restrictive nature. Supplementation with ketone drinks increase plasma β-hydroxybutyrate and mimics the metabolic effects of LCHF ketogenic diets as well as lowers BP and improves vascular and cognitive function in rodent models. Whether ketone supplementation lowers BP and improves vascular and cognitive health in humans of any age is unknown.
Approach: A double-blind randomized 2x2 crossover design with 2 repeated measures in each period will be used. Pre-/post-test evaluation in each period will be used to evaluate the benefits to vascular and cognitive health ingestion with consumption of a ketone drink/placebo drink.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Virginia
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Blacksburg, Virginia, United States, 24061
- Virginia Polytechnic and State University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Ability to provide informed consent
- 50-75 years of age
- Systolic blood pressure <160 mmHg
- Diastolic blood pressure <100 mmHg
- Sedentary to recreationally active
- Body Mass Index <35 kg/m^2
- Postmenopausal women must be >1 year since last menses
Exclusion Criteria:
- Current smoker
- Pregnant or planning to become pregnant
- Dyslipidemia (Total cholesterol >240 mg/dL, LDL >160 mg/dL)
- Chronic clinical disease (e.g., inflammatory bowel disease/irritable bowel syndrome, unstable coronary heart disease, stroke, heart failure, diabetes, neurological disorders)
- Following an extreme dietary pattern or planning to change to one (e.g., low carbohydrate, carnivore)
- Not weight stable in the prior 3 months (>2 kg weight change)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Dietary Ketone
Participants will consume three daily ketone drinks (one before each meal) for 2 weeks.
|
Pre- and post-testing will be completed before and after participants receive 42 doses of ketone supplement drink over a 2-week period (3x/day for 14 days).
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Placebo Comparator: Placebo
Participants will consume three daily placebo drinks (one before each meal) for 2 weeks. .
|
Pre- and post-testing will be completed before and after participants receive 42 doses of placebo supplement drink over a 2-week period (3x/day for 14 days).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Arterial Stiffness after Supplementation
Time Frame: 45-minute measurement in laboratory
|
The blood flow and diameter in the common arteries in the neck will be measured from the image obtained from an ultrasound unit (GE Vivid S6) equipped with a high-resolution linear array transducer.
For applanation tonometry, the carotid, brachial, radial and femoral artery pressure waveform and amplitude will be obtained by a fingertip probe incorporating a high-fidelity strain gauge transducer.
Each of these measures are used to calculate arterial stiffness.
These tests will be conducted two times separated by about 2 weeks.
The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design).
The supplement drink will be consumed 3 times per day, once before each meal.
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45-minute measurement in laboratory
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Change in Brachial Artery Function after Supplementation
Time Frame: 30-minute measurement in laboratory
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Brachial artery function or flow mediated dilation (FMD), the blood flow and diameter of the brachial artery in the forearm (fMD), will be measured using a duplex ultrasound machine before and after the inflation of a blood pressure cuff on the forearm for 5 minutes and after placing a nitroglycerine tablet (0.4 mg) under the participant's tongue.
This test will be conducted two times separated by about 2 weeks.
The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design).
The supplement drink will be consumed 3 times per day, once before each meal.
Off-line analysis of baseline and post-reactive hyperemic diameters and velocities will be performed using edge detection software (Vascular Analysis Tools, Medical Imaging Applications, Inc.).
|
30-minute measurement in laboratory
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Blood Pressure after Supplementation
Time Frame: 15-minute measurement in laboratory
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Blood pressure measurements will be made under quiet, comfortable ambient laboratory conditions via mercury sphygmomanometry.
Three consecutive measurements within 6mmHg will be averaged.
This measurement will be conducted two times separated by about 2 weeks.
The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design).
The supplement drink will be consumed 3 times per day, once before each meal.
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15-minute measurement in laboratory
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Change in Glucose Tolerance after Supplementation
Time Frame: 2-hour test in laboratory
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Participants will complete an oral glucose tolerance test, which includes having each subject consume a sugary glucose drink (75 grams) and collecting small amounts (less than one half teaspoon) of blood every half hour (4 blood draws) for a 2-hour period.
These tests will be conducted two times separated by about 2 weeks.
Each participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design).
The supplement drink will be consumed 3 times per day, once before each meal.
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2-hour test in laboratory
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Change in 24-hour Area Under the Curve for Glucose Levels after Supplementation
Time Frame: 3-day measurement during free living
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Glucose will be monitored by a Continuous Glucose Monitor (CGM) sensor (Enlite Sensor, Medtronic, Inc. or FreeStyle Libre, Abbott) and this will be placed on the subject's abdomen or back of the upper arm in order to measure glucose continuously.
The measured glucose levels will be assessed by an iPro2 Professional CGM, Medtronic, Inc. or FreeStyle Libre Pro CGM, Abbott and the CGM will be worn for consecutive 3 days.
These tests will be conducted two times separated by about 2 weeks.
The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design).
The supplement drink will be consumed 3 times per day, once before each meal.
|
3-day measurement during free living
|
Change in Executive Cognitive Function after Supplementation
Time Frame: 40-min measurement in laboratory
|
Participants will be instructed to complete a set of computerized tasks to asses executive cognitive function (e.g., working memory), speed of processing, and semantic verbal fluency.
These tests will be conducted two times separated by about 2 weeks.
The participant will be randomly-assigned to a supplement drink (ketone or placebo) followed by a 2-week washout period (crossover design).
The supplement drink will be consumed 3 times per day, once before each meal.
|
40-min measurement in laboratory
|
Collaborators and Investigators
Investigators
- Principal Investigator: Kevin Davy, PhD, Virginia Polytechnic Institute and State University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- 19-440
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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