Clinical trial NCT06867471: Effects of Exogenous Ketosis on Proteinuria and Renal Function
Official title: Effects of Exogenous Ketosis on Proteinuria and Renal Function in Patients with Chronic Kidney Disease and Patients with Polycystic Kidney Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Renal Insufficiency, Chronic
Polycystic Kidney Diseases
Proteinuria
Ketosis
Keywords: Kidney physiology
Glomerular Filtration Rate
Chronic Kidney disease
Ketosis
Proteinuria
Natriuresis
Lead sponsor: Gødstrup Hospital
Sponsor class: OTHER
First posted: 2025-03-10
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: A randomized, placebo-controlled, double-blinded crossover study will be conducted. Fourteen patients with polycystic kidney disease (PKD) and 29 patients with proteinuric kidney disease will receive ketone bodies (Ketone-IQ) and placebo in a randomized order. Each treatment period is four weeks. There will be a wash-out period of two weeks in between treatment periods. Effect variables will be measured in the last day of each treatment period.

Detailed description: Background: Until recently, the only treatment shown to slow progression of chronic kidney disease (CKD) has been angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

The use of sodium glucose transporter 2 (SGLT2)-inhibitors, which work by blocking the activity of sodium-glucose-cotransporter 2 channels in the proximal kidney tubule, has completely transformed the treatment of proteinuric kidney disease, with a 28% decrease in the risk for cardiorenal outcomes. Despite these new treatment options, a significant proportion of patients still succumb to kidney failure, require hospitalization for heart failure and die prematurely. Thus, additional preventive measures are essential.

Renewed interest in the physiological role of ketone bodies (KB) has emerged. It has become increasingly clear that ketosis has several beneficial effects including anti-epileptic effects, improved exercise capacity, lipid profile, cardiac function and cognition.

However, only few clinical studies have studied renal effects of exogenous ketosis, and to our knowledge there are no clinical studies examining the effects long term effects of renal ketosis in patients with CKD.

Hypothesis: Ketosis decreases urine albumin to creatinine ratio (ACR) and glomerular filtration rate (GFR) in patients with CKD/PKD.

Methods: A randomized, placebo-controlled, double-blinded crossover study will be conducted. Twenty-nine patients with proteinuric kidney disease (study a) and 14 patients with PKD (study b) will receive ketone bodies (Ketone-IQ) and placebo in a randomized order. Each treatment period is four weeks. There will be a wash-out period of two weeks in between treatment periods. Effect variables will be measured in the last day of each treatment period.

Perspectives: The study has the potential to provide information regarding the therapeutic potential of ketone bodies in patients with CKD/PKD.

Eligibility criteria: Inclusion Criteria

Study A (patients with CKD):

* ACR \> 200 mg/g \<3000 mg/g
* eGFR \>30 ml/min/1,73m2
* Treatment with Renin-Angiotension System (RAS) blockers and SGLT-2 inhibitors for a minimum of 4 weeks prior to inclusion
* Safe contraception if women in childbearing age

Study B (patients with PKD):

* Prior diagnose with PKD
* eGFR \>30 ml/min/1,73m2
* Treatment with Renin-Angiotension System (RAS) blockers for a minimum of 4 weeks prior to inclusion
* Safe contraception if women in childbearing age

Exclusion Criteria (Study A+B)

* Diabetes Mellitus type 1
* Heart Failure
* Liver Disease
* Kidney transplant
* Malignant diseases (except skin cancer)
* Recent acute myocardial infarction (AMI), apoplexia/transient ischemic attack (TIA) (within 3 months of inclusion)
* Pregnancy or breast feeding
* Alcohol or drug abuse
* Periodic fasting within four weeks of inclusion
* Routinely intake of ketogenic diet within four weeks of inclusion
* Treatment with nitrate

Primary outcomes:
measure: Proteinuria
timeFrame: Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks)
measure: GFR
timeFrame: Measured on the last day in each treatment period (each treatment period is 4 weeks)
Secondary outcomes:
measure: Aldosterone
timeFrame: Measured on the last day in each treatment period (each treatment period is 4 weeks)
measure: P-Beta-hydroxybutyrate
timeFrame: Measured on the last day in each treatment period (each treatment period is 4 weeks)
measure: Excretion rate of renal tubular transport proteins
timeFrame: Measured on the last day in each treatment period (each treatment period is 4 weeks)
measure: 24-hour Ambulatory Blood Pressure
timeFrame: Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)
measure: Sodium and potassium excretion
timeFrame: Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks)
measure: Peripherial Vascular Resistance
timeFrame: Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)
measure: Heart rate
timeFrame: Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)
measure: Pulse Wave Velocity
timeFrame: Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)
measure: Renin
timeFrame: Measured on the last day in each treatment period (each treatment period is 4 weeks)
Other outcomes:
Locations:
city: Herning
country: Denmark
facility: University Clinic in Nephrology and Hypertension, Gødstrup Region Hospital
state: Jutland
Study officials:
affiliation: University Clinic in Nephrology and Hypertenion, Godstrup Region Hospital
name: Trine Z Lyksholm, MD
role: PRINCIPAL_INVESTIGATOR
References: