Cardiovascular Diseases in Old AgeNCT05888506
Ketone Ester Supplementation and Nocturnal Blood Pressure
A study testing Ketone Ester in people with Cardiovascular Diseases in Old Age and Aging, run by Georgia Southern University at 1 site in United States.
Trial summary
Cardiovascular disease (CVD) is the number one cause of death globally and high blood pressure (i.e., hypertension) is the leading modifiable risk factor for CVD and all-cause mortality. Advancing age is the primary risk factor for hypertension and CVD. Read more about this study
- Who is it for?
- Ages 50 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases in Old Age, Aging, Cardiovascular Diseases
- What is being tested?
- Ketone Ester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2023to 3 Oct 2023
- Phase
- Interventional
- 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 50 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Greater than or equal to 50 years of age
- Body mass index (BMI) below 40 kg/m^2
- No alterations to use of prescription medication within the past 6 months
Who cannot join
- Alterations to use of prescription medication within the past 6 months
- Allergy to any of the ingredients in the ketone beverage
- Communication barriers
Trial locations and contacts
1 site in 1 country.
United States1 site
Biodynamics and Human Performance Center
Savannah, Georgia, 31419
About this study
Official title: The Effects of Ketone Ester Supplementation on Nocturnal Blood Pressure in Middle-Aged and Older Adults
Cardiovascular disease (CVD) is the number one cause of death globally and high blood pressure (i.e., hypertension) is the leading modifiable risk factor for CVD and all-cause mortality. Advancing age is the primary risk factor for hypertension and CVD. Moreover, compared to younger adults, older adults exhibit reduced nocturnal dipping of blood pressure resulting in elevated nighttime blood pressure values, which are a better predictor of cardiovascular outcomes than daytime blood pressure. Intriguingly, recently published rodent data suggests that ketone supplementation protects against hypertension, blood vessel dysfunction, and kidney injury. Whether ketone supplementation provides vascular health benefits in humans remains to be determined. Therefore, the investigations seek to conduct an acute ketone supplementation study to determine whether ketone supplementation may restore a more healthy nighttime blood pressure phenotype in middle-aged and older adults. The investigations will also determine whether ketone supplementation influences nocturnal heart rate variability, a non-invasive of autonomic function that may be influenced by ketone supplementation in a manner that influences blood pressure.
Read the detailed description
Cardiovascular disease (CVD) is the leading cause of death globally, killing one American approximately every 40 seconds. Among known risk factors, hypertension, or high blood pressure (BP), is the most important risk factor for the development of CVD. While sleeping, a healthy adult will experience a blood pressure dip of about 10% compared to resting values while awake. However, advancing age is associated with reduced blood pressure dipping, which is linked with an increased risk for CVD. Moreover, attenuated blood pressure dipping results in elevated nighttime blood pressure, which is in general a better predictor of cardiovascular outcomes than daytime blood pressure.
The autonomic nervous system plays a key role in blood pressure regulation and autonomic dysregulation is implicated in the pathophysiology of hypertension. Advancing age is associated with structural and function changes in the autonomic nervous system, which likely contribute, at least in part, to the marked elevation in the prevalence of hypertension and CVD that is observed in older adults. Heart rate variability (HRV) is an inexpensive and accessible index of autonomic function that is shown to decline rapidly form the second to fifth decades of life. Thus, strategies to improve nocturnal HRV may help to restore a more healthy nighttime blood pressure phenotype. However, this remains to be proven. Moreover, the link between aging, nocturnal HRV, and nighttime blood pressure is unclear.
Hypertension costs the United States between $131 and $198 billion dollars each year. Therefore, there exists a critical need to find ways to mitigate these negative health effects and costs to both the American public, and populations across the globe. Interestingly, there is a small but emerging body of evidence suggesting that ketone bodies may positively impact endothelial function and vascular health. In rodents, ketone supplementation prevents high-salt induced increase in blood pressure, blood vessel dysfunction, and kidney injury. However, there is a lack of data regarding whether ketone supplementation may provide similar cardiovascular health benefits in humans. Thus, in this first-of-kind placebo-controlled, randomized crossover design acute ketone supplementation study the investigations will evaluate the hypothesis that acute ketone supplementation will improve nocturnal blood pressure and HRV in middle-aged and older adults.
- Being tested
- Ketone Ester, Placebo
- Keywords
- blood pressure, sleep, heart rate variability, ketone ester
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone EsterDietary supplement
Participants will consume the ketone ester beverage produced by KetoneAid prior to bedtime. Participants will consume 60 mL (30 grams ketones) of the ketone beverage.
PlaceboDietary supplement
Participants will consume the placebo supplement prior to bedtime. The placebo supplement will be a ketone ester-free, taste and viscosity-matched, beverage produced by KetoneAid.
| Study group | Role | What they receive |
|---|---|---|
| Ketone Ester | Experimental | Participants will consume the supplement prior to bedtime. Nocturnal blood pressure, heart rate, and sleep characteristics will be assessed Receives: Dietary Supplement: Ketone Ester |
| Placebo Supplement | Placebo comparator | Participants will consume the supplement prior to bedtime. Nocturnal blood pressure, heart rate, and sleep characteristics will be assessed Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nocturnal blood pressure dipping
The investigations will use ambulatory blood pressure monitoring to characterize night-to-day blood pressure ratio
Measured: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary outcomes (8)
Nighttime blood pressure
The investigations will use ambulatory blood pressure monitoring to characterize nighttime blood pressure (mmHg)
Measured: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Nighttime heart rate variability
The investigators will use a single-lead electrocardiograph to characterize nocturnal heart rate variability (ms)
Measured: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Objective sleep duration
Actigraph accelerometers will be used to quantify sleep duration
Measured: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Objective sleep efficiency
Actigraph accelerometers will be used to quantify % of time in bed actually spent sleeping to calculate sleep efficiency
Measured: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Subjective sleep quality
A single-item visual analogue sleep scale will be used to quantify subjective sleep quality (i.e., 0 to 100, with a higher score indicating better sleep)
Measured: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Subjective sleep quality
The investigators will use the Pittsburgh Sleep Quality Index (PSQI) to assess perceived sleep quality reflective of the one month period leading into the study. PSQI scores range from 0-21, with a higher score indicting worse sleep.
Measured: Pre-intervention
Pulse wave analysis
The investigators will use the SphygmoCor XCEL system to assess pulse wave analysis (PWA) The sampling site is the brachial artery (upper alarm instrumented with a cuff for oscillometric sphygmomanometer).
Measured: Pre-intervention
Pulse wave velocity
The investigators will use the SphygmoCor XCEL system to assess pulse wave velocity (PWV). A high-fidelity strain-gauge transducer is used to obtain the pressure waveform at the carotid pulse. Distances from the carotid artery sampling site to the femoral artery (upper leg instrumented with a thigh cuff for oscillometric sphygmomanometry), and from the carotid artery to the suprasternal notch will be recorded. PWV will be expressed as m/s.
Measured: Pre-intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2023
- Study start1 Aug 2023
- Primary completion1 Oct 2023
- Study completion3 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular Diseases in Old AgeStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgia Southern University
- Sponsor type
- University, hospital or other
- Collaborators
- Auburn University
- Responsible party
- Sponsor
- Investigators
- Gregory J Grosicki, PhD, Principal investigator, Georgia Southern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05888506
- Sponsor's protocol ID
- H23223
- Status last verified
- Oct 2023
- First submitted
- 5 Apr 2023
- Last updated
- 6 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008 Jan;51(1):55-61. doi: 10.1161/HYPERTENSIONAHA.107.100727. Epub 2007 Nov 26.
PubMed 18039980Valensi P. Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications. Cardiovasc Diabetol. 2021 Aug 19;20(1):170. doi: 10.1186/s12933-021-01356-w.
PubMed 34412646Chakraborty S, Galla S, Cheng X, Yeo JY, Mell B, Singh V, Yeoh B, Saha P, Mathew AV, Vijay-Kumar M, Joe B. Salt-Responsive Metabolite, beta-Hydroxybutyrate, Attenuates Hypertension. Cell Rep. 2018 Oct 16;25(3):677-689.e4. doi: 10.1016/j.celrep.2018.09.058.
PubMed 30332647
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Ketone Ester Supplementation on Nocturnal Blood Pressure in Middle-Aged and Older Adults
- ClinicalTrials.gov ID
- NCT05888506
- Acronym / sponsor ID
- H23223
- Keywords
- blood pressure, sleep, heart rate variability, ketone ester
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Georgia Southern UniversityUniversity, hospital or other
- Collaborators
- Auburn University
- Study start
- 1 Aug 2023 (actual)
- Primary completion
- 1 Oct 2023 (actual)
- Study completion
- 3 Oct 2023 (actual)
- First posted
- 5 Jun 2023 (actual)
- 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.
Cardiovascular disease (CVD) is the number one cause of death globally and high blood pressure (i.e., hypertension) is the leading modifiable risk factor for CVD and all-cause mortality. Advancing age is the primary risk factor for hypertension and CVD. Moreover, compared to younger adults, older adults exhibit reduced nocturnal dipping of blood pressure resulting in elevated nighttime blood pressure values, which are a better predictor of cardiovascular outcomes than daytime blood pressure. Intriguingly, recently published rodent data suggests that ketone supplementation protects against hypertension, blood vessel dysfunction, and kidney injury. Whether ketone supplementation provides vascular health benefits in humans remains to be determined. Therefore, the investigations seek to conduct an acute ketone supplementation study to determine whether ketone supplementation may restore a more healthy nighttime blood pressure phenotype in middle-aged and older adults. The investigations will also determine whether ketone supplementation influences nocturnal heart rate variability, a non-invasive of autonomic function that may be influenced by ketone supplementation in a manner that influences blood pressure.
Detailed description
Cardiovascular disease (CVD) is the leading cause of death globally, killing one American approximately every 40 seconds. Among known risk factors, hypertension, or high blood pressure (BP), is the most important risk factor for the development of CVD. While sleeping, a healthy adult will experience a blood pressure dip of about 10% compared to resting values while awake. However, advancing age is associated with reduced blood pressure dipping, which is linked with an increased risk for CVD. Moreover, attenuated blood pressure dipping results in elevated nighttime blood pressure, which is in general a better predictor of cardiovascular outcomes than daytime blood pressure.
The autonomic nervous system plays a key role in blood pressure regulation and autonomic dysregulation is implicated in the pathophysiology of hypertension. Advancing age is associated with structural and function changes in the autonomic nervous system, which likely contribute, at least in part, to the marked elevation in the prevalence of hypertension and CVD that is observed in older adults. Heart rate variability (HRV) is an inexpensive and accessible index of autonomic function that is shown to decline rapidly form the second to fifth decades of life. Thus, strategies to improve nocturnal HRV may help to restore a more healthy nighttime blood pressure phenotype. However, this remains to be proven. Moreover, the link between aging, nocturnal HRV, and nighttime blood pressure is unclear.
Hypertension costs the United States between $131 and $198 billion dollars each year. Therefore, there exists a critical need to find ways to mitigate these negative health effects and costs to both the American public, and populations across the globe. Interestingly, there is a small but emerging body of evidence suggesting that ketone bodies may positively impact endothelial function and vascular health. In rodents, ketone supplementation prevents high-salt induced increase in blood pressure, blood vessel dysfunction, and kidney injury. However, there is a lack of data regarding whether ketone supplementation may provide similar cardiovascular health benefits in humans. Thus, in this first-of-kind placebo-controlled, randomized crossover design acute ketone supplementation study the investigations will evaluate the hypothesis that acute ketone supplementation will improve nocturnal blood pressure and HRV in middle-aged and older adults.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketone Ester | Experimental | Dietary Supplement: Ketone EsterParticipants will consume the supplement prior to bedtime. Nocturnal blood pressure, heart rate, and sleep characteristics will be assessed |
| Placebo Supplement | Placebo comparator | Dietary Supplement: PlaceboParticipants will consume the supplement prior to bedtime. Nocturnal blood pressure, heart rate, and sleep characteristics will be assessed |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Greater than or equal to 50 years of age
- Body mass index (BMI) below 40 kg/m^2
- No alterations to use of prescription medication within the past 6 months
Key exclusion criteria (3 listed)
- Alterations to use of prescription medication within the past 6 months
- Allergy to any of the ingredients in the ketone beverage
- Communication barriers
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 |
|---|---|---|
| Ketone EsterParticipants will consume the ketone ester beverage produced by KetoneAid prior to bedtime. Participants will consume 60 mL (30 grams ketones) of the ketone beverage. | Dietary supplement | Ketone Ester |
| PlaceboParticipants will consume the placebo supplement prior to bedtime. The placebo supplement will be a ketone ester-free, taste and viscosity-matched, beverage produced by KetoneAid. | Dietary supplement | Placebo Supplement |
Primary outcome
Nocturnal blood pressure dipping
Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
The investigations will use ambulatory blood pressure monitoring to characterize night-to-day blood pressure ratio
8 secondary outcomes
Nighttime blood pressure
Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Nighttime heart rate variability
Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Objective sleep duration
Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Objective sleep efficiency
Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Subjective sleep quality
Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Subjective sleep quality
Time frame: Pre-intervention
Pulse wave analysis
Time frame: Pre-intervention
Pulse wave velocity
Time frame: Pre-intervention
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 6 Oct 2023.
- Background: PubMed 18039980Fagard RH, Celis H, Thijs L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer DA. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008 Jan;51(1):55-61. doi: 10.1161/HYPERTENSIONAHA.107.100727. Epub 2007 Nov 26.
- Background: PubMed 34412646Valensi P. Autonomic nervous system activity changes in patients with hypertension and overweight: role and therapeutic implications. Cardiovasc Diabetol. 2021 Aug 19;20(1):170. doi: 10.1186/s12933-021-01356-w.
- Background: PubMed 30332647Chakraborty S, Galla S, Cheng X, Yeo JY, Mell B, Singh V, Yeoh B, Saha P, Mathew AV, Vijay-Kumar M, Joe B. Salt-Responsive Metabolite, beta-Hydroxybutyrate, Attenuates Hypertension. Cell Rep. 2018 Oct 16;25(3):677-689.e4. doi: 10.1016/j.celrep.2018.09.058.
- Individual participant dataSharing planned: No
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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.
Gregory J Grosicki, PhD principal investigator
Georgia Southern University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone Ester in people with Cardiovascular Diseases in Old Age and Aging, run by Georgia Southern University 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 3 inclusion and 3 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 6 Oct 2023. 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. 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.
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?
Nocturnal blood pressure dipping (time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)). 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 NCT05888506, which also lists 3 linked publications.
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 6 Oct 2023.