Effects of Exogenous Ketosis on Proteinuria and Renal Function (KETO-CKD)

Gødstrup Hospital

Status: Enrolling

Conditions: Proteinuria; Ketosis; Polycystic Kidney Diseases; Renal Insufficiency, Chronic

Treatments: Dietary Supplement: Ketone Diol, R-1,3-butanediol (Ketone-IQ); Other: Placebo drink

Study type: Interventional

Funder types: Other

Identifiers

NCT06867471

TZL-2-2024

Details and patient eligibility

About

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.

Full 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.

Enrollment: 43 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

43 participants in 2 patient groups

Ketone diol (Ketone-IQ), then Placebo drink

Other group

Description:

For four weeks each subject will receive Ketone Diol, R-1,3-butanediol, administered as a drink (Ketone-IQ) twice a day, then crossed over to receive a taste and volume matched placebo drink for four weeks. Each individual will receive 400mg/kg before bedtime in addition to 200mg/kg with a minimum of 6 hours in between throughout the treatment period.

Treatment:

Other: Placebo drink

Dietary Supplement: Ketone Diol, R-1,3-butanediol (Ketone-IQ)

Placebo drink, then Ketone diol (Ketone-IQ)

Other group

Description:

For four weeks each subject will receive a placebo drink twice a day, then crossed over to receive Ketone Diol, R-1,3-butanediol, administered as a drink (Ketone-IQ) twice a day for four weeks. Each individual will receive 400mg/kg before bedtime in addition to 200mg/kg with a minimum of 6 hours in between throughout the treatment period.

Treatment:

Other: Placebo drink

Dietary Supplement: Ketone Diol, R-1,3-butanediol (Ketone-IQ)