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Completed

NCT Number: NCT05888506

Ketone Ester Supplementation and Nocturnal Blood Pressure

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.

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Key information

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Biodynamics and Human Performance Center

Savannah, Georgia, 31419, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • Alterations to use of prescription medication within the past 6 months
  • Allergy to any of the ingredients in the ketone beverage
  • Communication barriers

Treatment and study plan

Ketone ester

Dietary 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.

Placebo

Dietary 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.

Primary outcomes

  1. 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

Secondary outcomes

  1. Nighttime blood pressure

    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 nighttime blood pressure (mmHg)

  2. Nighttime heart rate variability

    Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)

    The investigators will use a single-lead electrocardiograph to characterize nocturnal heart rate variability (ms)

  3. Objective sleep duration

    Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)

    Actigraph accelerometers will be used to quantify sleep duration

  4. Objective sleep efficiency

    Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)

    Actigraph accelerometers will be used to quantify % of time in bed actually spent sleeping to calculate sleep efficiency

  5. Subjective sleep quality

    Time frame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)

    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)

  6. Subjective sleep quality

    Time frame: Pre-intervention

    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.

  7. Pulse wave analysis

    Time frame: Pre-intervention

    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).

  8. Pulse wave velocity

    Time frame: Pre-intervention

    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.

Sponsors and collaborators

Lead sponsor

Georgia Southern University

Other

Collaborators

  • Auburn University

Registry information

Official study title

The Effects of Ketone Ester Supplementation on Nocturnal Blood Pressure in Middle-Aged and Older Adults

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Jun 5, 2023
Registry last updated
Oct 6, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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