Clinical trial NCT05888506: Ketone Ester Supplementation and Nocturnal Blood Pressure
Official title: The Effects of Ketone Ester Supplementation on Nocturnal Blood Pressure in Middle-Aged and Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases in Old Age
Aging
Cardiovascular Diseases
Sleep
Keywords: blood pressure
sleep
heart rate variability
ketone ester
Lead sponsor: Georgia Southern University
Sponsor class: OTHER
Collaborators: name: Auburn University
First posted: 2023-06-05
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: 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

Primary outcomes:
measure: Nocturnal blood pressure dipping
timeFrame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
Secondary outcomes:
measure: Nighttime blood pressure
timeFrame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
measure: Nighttime heart rate variability
timeFrame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
measure: Objective sleep duration
timeFrame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
measure: Objective sleep efficiency
timeFrame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
measure: Subjective sleep quality
timeFrame: Night one of supplement ingestion (i.e., from time asleep to time awake for one night per condition)
measure: Subjective sleep quality
timeFrame: Pre-intervention
measure: Pulse wave analysis
timeFrame: Pre-intervention
measure: Pulse wave velocity
timeFrame: Pre-intervention
Other outcomes:
Locations:
city: Savannah
country: United States
facility: Biodynamics and Human Performance Center
state: Georgia
Study officials:
affiliation: Georgia Southern University
name: Gregory J Grosicki, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Valensi 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.
citation: Chakraborty 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.