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

Essential Hypertension Clinical Trial

— (KETO-HT)  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06418074
• Other study ID #: TZL-1-2024
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2024
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Gødstrup Hospital
• Contact: Trine Z Lykshom, MD
• Phone: 78432534
• Email: trizur[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 19
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Essential Hypertension
• Hypertension
• Ketosis

Intervention

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.

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gødstrup Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24-hour systolic blood pressure	Change in systolic 24-hour blood pressure	Measured after each treatment period (each treatment period is 6 days)
Secondary	Renal Blood Flow (RBF)	Change in RBF determined by water based PET/CT scans	Measured after each treatment period (each treatment period is 6 days)
Secondary	GFR	Change in GFR measured by Tc99m-DTPA clearance	Measured after each treatment period (each treatment period is 6 days)
Secondary	Vasoactive hormones	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)
Secondary	P-Beta-hydroxybutyrate	Change ind p-beta-hydroxybutyrate concentration	Measured after each treatment period (each treatment period is 6 days)
Secondary	Plasma concentration of 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 (each treatment period is 6 days)