Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity in Healthy Subjects (KETO)

This is a randomized, placebo-controlled, double-blinded crossover design. Fifteen healthy subjects 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).

Study Overview

• Status: Completed
• Conditions: Ketosis; Ketonemia
• Intervention / Treatment: Dietary supplement: Beta-hydroxybutyrate; Other: Placebo

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 increases renal blood flow and glomerular filtration rate (GFR).

Methods: It is a randomized, placebo-controlled double-blinded cross over study. Fifteen healthy subjects 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
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Jutland
    • Herning, Jutland, Denmark, 7400
      • The University Clinic of Nephrology and Hypertension

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI < 30 kg/m2
• Safe contraception if women in childbearing age
• Normal biochemical screening

Exclusion Criteria:

• Pregnancy or breast feeding
• Major heart-, liver-, kidney-, lung-, neurological- or endocrine disease
• Daily use of prescription drugs (expect for contraceptives)
• Alcohol or drug abuse
• Periodic fasting
• Routinely intake of ketogenic diet

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: KetoneAid KE4, then Placebo drink; For five days each subject will receive beta-hydroxybutyrate (KE4), then crossed over to receive placebo drink for 5 days.	Dietary supplement: Beta-hydroxybutyrate; Each subject receive Beta-hydroxybutyrate 300mg/kg x 3 for five days. After the treatment period effect variables will be examined.; Other: Placebo; Each subject receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.
Active Comparator: Placebo drink, then KetoneAid KE4; For five days each subject will receive a placebo drink three times daily, then subjects are crossed over to receive beta-hydroxybutyrate (KE4).	Dietary supplement: Beta-hydroxybutyrate; Each subject receive Beta-hydroxybutyrate 300mg/kg x 3 for five days. After the treatment period effect variables will be examined.; Other: Placebo; Each subject receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GFR	Change in GFR measured by Tc99m-DTPA clearance	Measured after each treatment period (day 6 and approximately day 26)
Renal Blood Flow (RBF)	Change in RBF determined by water based PET/CT scans	Subjects are scanned after each treatment period (day 6 and approximately day 26)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour blood pressure	Change in systolic 24-hour blood pressure	Measured after each treatment period (day 6 and approximately day 26)
Vasoactive hormones	Change in plasma levels of angiotensin II, aldosterone, renin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), copeptin	Measured after each treatment period (day 6 and approximately day 26)
Beta-hydroxybutyrate	Change ind p-beta-hydroxybutyrate	Measured after each treatment period (day 6 and approximately day 26)
Renal tubular transport proteins	Urine excretions of aquaporin 2 (AQP2), thiazide-sensitive sodium-chloride cotransporter (NCC) and distal epithelial sodium channel (ENaC)	Measured after each treatment period (day 6 and approximately day 26)

Collaborators and Investigators

• Sponsor: Gødstrup Hospital
• Investigators: Principal Investigator: Jesper N Bech, PhD, Prof, University Clinic in Nephrology and Hypertension

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2023
• Primary Completion (Actual): April 11, 2024
• Study Completion (Actual): April 11, 2024

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Kidney function; Glomerular Filtration Rate; Kidney circulation; Kidney physiology
• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis; Ketosis
• Other Study ID Numbers: TZL-2-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No