This is a randomized, placebo-controlled, double-blinded crossover design. Nineteen patients with essential hypertension will be randomized to receive either ketone bodies (KE4) or placebo delivered by KetoneAid. After a period of 5-days treatment, effect variables will be measured (experiment day 1). After a washout period of 14 days, the subjects are crossed over to a similar treatment period with the other treatment. The study is terminated by measuring effect variables after the second treatment period (experiment day 2).
Background: Renewed interest in ketone bodies has emerged, partly driven by the recent success of selective sodium glucose co transporter 2 (SGLT-2) inhibition in preventing cardiovascular deaths in patients with diabetes mellitus (DM) and chronic kidney disease (CKD). Effects of ketosis are of importance in order to understand the beneficial effects of SGLT-2 inhibitors and to account for the full therapeutic potential of this treatment. Hypothesis: Ketosis decreases 24 hour systolic blood pressure and increases renal blood flow and glomerular filtration rate (GFR). Methods: It is a randomized, placebo-controlled double-blinded cross over study. Nineteen patients with essential hypertension will be randomized to receive either ketone bodies (KE4) or for 5 days. After a wash out period of at least 14 days, the subjects are crossed over to receive the other treatment. After each treatment period effect variables will be measured including Technetium(Tc)99m - Diethylenetriamine pentaacetate (DTPA) clearance and water based positron emission tomography computed tomography (PET/CT) Perspectives: The study has the potential to provide information regarding the therapeutic potential of treatment with ketone bodies and understanding of conditions characterized by ketosis, such as SGLT2-inhibitor treatment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
Each subject will receive beta-hydroxybutyrate boned to R 1,3 Butandiol (KE4) 300mg/kg x 3 for five days. After the treatment period effect variables will be examined.
Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.
The University Clinic in Nephrology and Hypertension, Gødstrup Region Hospital
Herning, Denmark
24-hour systolic blood pressure
Change in systolic 24-hour blood pressure
Time frame: Measured after each treatment period (each treatment period is 6 days)
Renal Blood Flow (RBF)
Change in RBF determined by water based PET/CT scans
Time frame: Measured after each treatment period (each treatment period is 6 days)
GFR
Change in GFR measured by Tc99m-DTPA clearance
Time frame: Measured after each treatment period (each treatment period is 6 days)
Vasoactive hormones
Change in plasma levels of aldosterone, renin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), copeptin
Time frame: Measured after each treatment period (each treatment period is 6 days)
P-Beta-hydroxybutyrate
Change ind p-beta-hydroxybutyrate concentration
Time frame: Measured after each treatment period (each treatment period is 6 days)
Plasma concentration of renal tubular transport proteins
Urine excretions of aquaporin 2 (AQP2), thiazide-sensitive sodium-chloride cotransporter (NCC) and distal epithelial sodium channel (ENaC)
Time frame: Measured after each treatment period (each treatment period is 6 days)
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