Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity

Not Applicable

Recruiting

• Conditions: Ketosis; Essential Hypertension
• Interventions: Dietary Supplement: Ketone Monoester (KE4); Other: Placebo

• Registration Number: NCT06418074
• Lead Sponsor: Gødstrup Hospital

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.

Study Timeline

• Study First Submitted: 2024-05-06
• Study First Submitted QC: 2024-05-13
• Study First Posted: 2024-05-16
• Study Start: 2024-09-11
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-20
• Last Update Posted: 2024-11-22
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 19

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ketone Monoester (KE4), then Placebo drink	Placebo	For five days each subject will receive beta-hydroxybutyrate boned to R 1,3 Butandiol (KE4), then crossed over to receive placebo drink for 5 days.
Placebo drink, then Ketone Monoester (KE4)	Ketone Monoester (KE4)	For five days each subject will receive a placebo drink three times daily, then subjects are crossed over to receive beta-hydroxybutyrate boned to R 1,3 Butandiol (KE4).
Ketone Monoester (KE4), then Placebo drink	Ketone Monoester (KE4)	For five days each subject will receive beta-hydroxybutyrate boned to R 1,3 Butandiol (KE4), then crossed over to receive placebo drink for 5 days.
Placebo drink, then Ketone Monoester (KE4)	Placebo	For five days each subject will receive a placebo drink three times daily, then subjects are crossed over to receive beta-hydroxybutyrate boned to R 1,3 Butandiol (KE4).

Primary Outcome Measures

Name	Time	Method
24-hour systolic blood pressure	Measured after each treatment period (each treatment period is 6 days)	Change in systolic 24-hour blood pressure

Secondary Outcome Measures

Name	Time	Method
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
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)
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

Trial Locations

Locations (1)

The University Clinic in Nephrology and Hypertension, Gødstrup Region Hospital; 🇩🇰 Herning, Denmark