Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketone diol (Ketone-IQ), then Placebo drink | Other | 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. |
|
| Placebo drink, then Ketone diol (Ketone-IQ) | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketone Diol, R-1,3-butanediol (Ketone-IQ) | Dietary Supplement | Effect variables will be measured on the last day of treatment with Ketone-IQ |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proteinuria | Mean difference between Log UACR after 4 weeks treatment with ketone bodies and placebo (primary outcome study a) | Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks) |
| GFR | Mean difference between GFR measured by Technetium99 (Tc99m) - Diethylene Triamine Pentaacetic Acid (DTPA) clearance after 4 weeks treatment with ketone bodies and placebo (primary outcome study b, secondary outcome in study a) | Measured on the last day in each treatment period (each treatment period is 4 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Aldosterone | Mean difference in plasma levels of aldosterone (pmol/L) after 4 weeks treatment with ketone bodies and placebo | Measured on the last day in each treatment period (each treatment period is 4 weeks) |
| P-Beta-hydroxybutyrate |
Not provided
Inclusion Criteria
Study A (patients with CKD):
Study B (patients with PKD):
Exclusion Criteria (Study A+B)
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Trine Z Lyksholm, MD | Contact | 78432534 | 0045 | trizur@rm.dk |
| Name | Affiliation | Role |
|---|---|---|
| Trine Z Lyksholm, MD | University Clinic in Nephrology and Hypertenion, Godstrup Region Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Clinic in Nephrology and Hypertension, Gødstrup Region Hospital | Recruiting | Herning | Jutland | 7400 | Denmark |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D007690 | Polycystic Kidney Diseases |
| D011507 | Proteinuria |
| D007662 | Ketosis |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Ketone-IQ and the placebo drink will be transferred to neutral bottles and relabeled. The local pharmacy will be handling the blinding and randomization.
| Placebo drink | Other | Effect variables will be measured on the last day of treatment with Placebo |
|
Change ind p-beta-hydroxybutyrate concentration
| Measured on the last day in each treatment period (each treatment period is 4 weeks) |
| Excretion rate of renal tubular transport proteins | Mean difference between urine excretion rate of aquaporin 2 (AQP2) (pq/min), thiazide-sensitive sodium-chloride cotransporter (NCC)(pg/min), and distal epithelial sodium channel (ENaC)(pg/min) after 4 weeks treatment with ketone bodies and placebo | Measured on the last day in each treatment period (each treatment period is 4 weeks) |
| 24-hour Ambulatory Blood Pressure | Mean difference between systolic and diastolic 24-hour ambulatory blood pressure (mmHg) after treatment with ketone bodies and placebo. | Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks) |
| Sodium and potassium excretion | Diffeence between mean fractional and absolute excretion af sodium and postassium after 4 weeks treatment with ketone bodies and placebo | Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks) |
| Peripherial Vascular Resistance | Mean difference between peripherial vascular resistance (dyn*s/cm5) during treatment with ketone bodies compared to placebo | Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks) |
| Heart rate | Mean difference between heart rate after 4 weeks treatment with ketone bodies and placebo | Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks) |
| Pulse Wave Velocity | Mean difference between pulse wave velocity (m/s) after 4 weeks treatment with ketone bodies and placebo | Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks) |
| Renin | Mean difference in plasma concentration of renin(pmol/L) after 4 weeks treatment with ketone bodies and placebo | Measured on the last day in each treatment period (each treatment period is 4 weeks) |
| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D052177 | Kidney Diseases, Cystic |
| D000015 | Abnormalities, Multiple |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D000072661 | Ciliopathies |
| D030342 | Genetic Diseases, Inborn |
| D014555 | Urination Disorders |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D000138 | Acidosis |
| D000137 | Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |