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

NCT ID: NCT06418074

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-11
• Study Completion Date: 2025-06-19

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.

Conditions

Ketosis; Essential Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Ketone Monoester (KE4), then Placebo drink

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.

Group Type: ACTIVE_COMPARATOR

Ketone Monoester (KE4)

Intervention Type: DIETARY_SUPPLEMENT

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.

Placebo

Intervention Type: OTHER

Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.

Placebo drink, then 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).

Group Type: PLACEBO_COMPARATOR

Ketone Monoester (KE4)

Intervention Type: DIETARY_SUPPLEMENT

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.

Placebo

Intervention Type: OTHER

Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.

Interventions

Ketone 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.

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gødstrup Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Trine Z Lyksholm, MD

Role: PRINCIPAL_INVESTIGATOR

The University Clinic for Nephrology and Hypertenion, Regional Hospital Godstrup

Locations

The University Clinic in Nephrology and Hypertension, Gødstrup Region Hospital

Herning, , Denmark

Countries

Denmark

Other Identifiers

TZL-1-2024

Identifier Type: -

Identifier Source: org_study_id