Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity ((KETO-HT))

June 3, 2024 updated by: Trine Lyksholm, Gødstrup Hospital

Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity in Patients With Essential Hypertension

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).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

19

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trine Z Lykshom, MD
  • Phone Number: 0045 78432534
  • Email: trizur@rm.dk

Study Contact Backup

  • Name: Jesper N Bech, MD, prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
Other: Placebo
Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.
Dietary supplement: 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.
Placebo Comparator: 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).
Other: Placebo
Each subject will receive a placebo drink 3 x day for five days. After the treatment period effect variables will be examined.
Dietary supplement: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24-hour systolic blood pressure
Time Frame: Measured after each treatment period (each treatment period is 6 days)
Change in systolic 24-hour blood pressure
Measured after each treatment period (each treatment period is 6 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Renal Blood Flow (RBF)
Time Frame: Measured after each treatment period (each treatment period is 6 days)
Change in RBF determined by water based PET/CT scans
Measured after each treatment period (each treatment period is 6 days)
GFR
Time Frame: Measured after each treatment period (each treatment period is 6 days)
Change in GFR measured by Tc99m-DTPA clearance
Measured after each treatment period (each treatment period is 6 days)
Vasoactive hormones
Time Frame: 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
Measured after each treatment period (each treatment period is 6 days)
P-Beta-hydroxybutyrate
Time Frame: Measured after each treatment period (each treatment period is 6 days)
Change ind p-beta-hydroxybutyrate concentration
Measured after each treatment period (each treatment period is 6 days)
Plasma concentration of renal tubular transport proteins
Time Frame: 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)
Measured after each treatment period (each treatment period is 6 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gødstrup Hospital

Investigators

  • Principal Investigator: Trine Z Lyksholm, MD, The University Clinic for Nephrology and Hypertenion, Regional Hospital Godstrup

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

May 6, 2024

First Submitted That Met QC Criteria

May 13, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Estimated)

June 4, 2024

Last Update Submitted That Met QC Criteria

June 3, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TZL-1-2024

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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