Effects of Exogenous Ketosis on Proteinuria and Renal Function in Patients With Chronic Kidney Disease and Patients With Polycystic Kidney Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 3
- 主要终点
- Proteinuria
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Ketone-IQ and the placebo drink will be transferred to neutral bottles and relabeled. The local pharmacy will be handling the blinding and randomization.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •(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
研究组 & 干预措施
Ketone diol (Ketone-IQ), then Placebo drink
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.
干预措施: Ketone Diol, R-1,3-butanediol (Ketone-IQ) (Dietary Supplement)
Ketone diol (Ketone-IQ), then Placebo drink
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.
干预措施: Placebo drink (Other)
Placebo drink, then Ketone diol (Ketone-IQ)
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.
干预措施: Ketone Diol, R-1,3-butanediol (Ketone-IQ) (Dietary Supplement)
Placebo drink, then Ketone diol (Ketone-IQ)
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.
干预措施: Placebo drink (Other)
结局指标
主要结局
Proteinuria
时间窗: Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks)
Mean difference between Log UACR after 4 weeks treatment with ketone bodies and placebo (primary outcome study a)
GFR
时间窗: Measured on the last day in each treatment period (each treatment period is 4 weeks)
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)
次要结局
- Aldosterone(Measured on the last day in each treatment period (each treatment period is 4 weeks))
- P-Beta-hydroxybutyrate(Measured on the last day in each treatment period (each treatment period is 4 weeks))
- Excretion rate of renal tubular transport proteins(Measured on the last day in each treatment period (each treatment period is 4 weeks))
- 24-hour Ambulatory Blood Pressure(Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks))
- Sodium and potassium excretion(Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks))
- Peripherial Vascular Resistance(Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks))
- Heart rate(Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks))
- Pulse Wave Velocity(Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks))
- Renin(Measured on the last day in each treatment period (each treatment period is 4 weeks))