Clinical trial NCT06418074: Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity
Official title: Effects of Exogenous Ketosis on Renal Function, Renal Perfusion, and Sodium Excretory Capacity in Patients with Essential Hypertension
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ketosis
Essential Hypertension
Keywords: Natriuresis
Kidney circulation
Kidney physiology
Glomerular Filtration Rate
Lead sponsor: Gødstrup Hospital
Sponsor class: OTHER
First posted: 2024-05-16
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: 24-hour systolic blood pressure
timeFrame: Measured after each treatment period (each treatment period is 6 days)
Secondary outcomes:
measure: Renal Blood Flow (RBF)
timeFrame: Measured after each treatment period (each treatment period is 6 days)
measure: GFR
timeFrame: Measured after each treatment period (each treatment period is 6 days)
measure: Vasoactive hormones
timeFrame: Measured after each treatment period (each treatment period is 6 days)
measure: P-Beta-hydroxybutyrate
timeFrame: Measured after each treatment period (each treatment period is 6 days)
measure: Plasma concentration of renal tubular transport proteins
timeFrame: Measured after each treatment period (each treatment period is 6 days)
Other outcomes:
Locations:
city: Herning
country: Denmark
facility: The University Clinic in Nephrology and Hypertension, Gødstrup Region Hospital
Study officials:
affiliation: The University Clinic for Nephrology and Hypertenion, Regional Hospital Godstrup
name: Trine Z Lyksholm, MD
role: PRINCIPAL_INVESTIGATOR
References: