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

Sponsor

Gødstrup Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05980858

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a randomized, placebo-controlled, double-blinded crossover design. Fifteen healthy subjects will be randomized to receive either ketone bodies or placebo. 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 and the study is terminated by measuring effect variables after the second treatment period (experiment day 2).

Condition or Disease	Intervention/Treatment	Phase
Ketosis Ketonemia	Dietary Supplement: Beta-hydroxybutyrate Other: Placebo	N/A

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 or placebo 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 Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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 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.

Arm

Intervention/Treatment

Active Comparator: 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 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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Gødstrup Hospital

Investigators

Principal Investigator: Jesper N Bech, PhD, Prof, University Clinic in Nephrology and Hypertension

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Trine Lyksholm, Principal investigator, Gødstrup Hospital

ClinicalTrials.gov Identifier:

NCT05980858

Other Study ID Numbers:

TZL-2-2023

First Posted:

Aug 8, 2023

Last Update Posted:

Aug 8, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Trine Lyksholm, Principal investigator, Gødstrup Hospital

Kidney circulation

Kidney physiology

Kidney function

Glomerular Filtration Rate

Additional relevant MeSH terms:

Ketosis

Study Results

No Results Posted as of Aug 8, 2023