Essential Hypertension, Ketosis
Conditions
Keywords
Natriuresis, Kidney circulation, Kidney physiology, Glomerular Filtration Rate
Brief summary
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).
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTKetone Monoester (KE4)
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.
OTHERPlacebo
Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.
Sponsors
Gødstrup Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Essential hypertension (treatment with maximum 2 antihypertensive drugs) * eGFR \> 60ml/min * BMI \< 35 kg/m2 * Urine Albumin Creatinin Ratio (UACR) \< 300mg/g * Safe contraception if women in childbearing age
Exclusion criteria
* Diabetes type 1 or 2 * Heart Failure * Pregnancy or breast feeding * Liver disease * Malignant disease * Recent acute myocardial infarction (AMI), apoplexia/transient ischemic attack (TIA) (within 12 months of inclusion) * Daily use of prescription drugs (expect for contraceptives) * Alcohol or drug abuse * Periodic fasting * Routinely intake of ketogenic diet * Treatment with immunosuppressants or SGLT2-inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour systolic blood pressure | Measured after each treatment period (each treatment period is 6 days) | Change in systolic 24-hour blood pressure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Renal Blood Flow (RBF) | Measured after each treatment period (each treatment period is 6 days) | Change in RBF determined by water based PET/CT scans |
| GFR | Measured after each treatment period (each treatment period is 6 days) | Change in GFR measured by Tc99m-DTPA clearance |
| Vasoactive hormones | Measured after each treatment period (each treatment period is 6 days) | Change in plasma levels of aldosterone, renin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), copeptin |
| P-Beta-hydroxybutyrate | Measured after each treatment period (each treatment period is 6 days) | Change ind p-beta-hydroxybutyrate concentration |
| Plasma concentration of renal tubular transport proteins | Measured after each treatment period (each treatment period is 6 days) | Urine excretions of aquaporin 2 (AQP2), thiazide-sensitive sodium-chloride cotransporter (NCC) and distal epithelial sodium channel (ENaC) |
Countries
Denmark
Outcome results
None listed