- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04680780
Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (Keto-ADPKD)
A mild reduction in food intake significantly inhibits renal cyst growth in mouse models of ADPKD. The underlying mechanism was unknown at the time. Recently published data show that the beneficial effect is not due to caloric restriction per se but due to the induction of the state of ketosis. Dietary interventions leading to ketosis profoundly inhibited renal cyst growth in rodent models of PKD. In addition, acute fasting led to rapid regression of renal cystic burden in mouse, rat and feline models of PKD. Due to these compelling effects in a multitude of PKD animal models, and due to the fact that well-established dietary interventions have a tremendous translational potential, KETO-ADPKD will test such interventions regimens in ADPKD patients.
Two well-established ketogenic dietary regimens will be tested in comparison to a control group to address the following four questions:
- Feasibility: Are ketogenic dietary interventions acceptable to ADPKD patients in everyday life?
- Safety: Are there adverse events of ketogenic dietary interventions in ADPKD patients?
- Efficacy: Do the dietary interventions reach the metabolic endpoints? Do they have a short-term impact on kidney volume?
- Which of the two diets is the optimal approach?
These questions will be addressed in an exploratory, randomized, open, single center, three-arm dietary intervention study using the following interventions in 21 ADPKD patients per treatment arm:
A) Ketogenic diet B) 3-day water fasting C) Control: ad libitum food intake (no diet)
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Cologne, Germany, 50937
- Department II of Internal Medicine, University Hospital of Cologne
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male and female ADPKD patients (based on genetics or imaging) ≥ 18 and ≤ 60 years
Indicators of rapid progression, either of the following:
- Mayo class 1C-E (measured on screening)
- Truncating PKD1 mutation,
- onset of arterial hypertension/urological symptoms < 35 years (patient history)
- first- or second degree family members reaching ESRD at < 60 years of age (patient history),
- eGFR loss > 2.5 ml/min/yr (as determined by at least 4 serum creatinine values within the last 4 years, with at least 6 months between each measurement ),
- PROPKD score > 6 (patient history)
- CKD-stages G1-3 as determined by eGFR (CKD-EPI)
- Written informed consent
Exclusion Criteria:
- Underweight or obese individuals ( as defined by BMI ≤ 18.5 kg/m2 or ≥ 35 kg/m2)
- Exposure to a ketogenic diet (classical ketogenic diet or modified Atkins)for more than 2 weeks within the last 6 months
- Participation in a weight-loss program within the last 6 months based on patient history
- Vegetarian / vegan lifestyle based on patient history
- Current treatment (or within the last 6 months) with tolvaptan or a somatostatin analogue based on patient history
- Inability to give informed consent
- Conditions prohibiting the use of a ketogenic diet (Liver damage, pancreatic failure, pyruvate-carboxylase deficiency, defects in fatty acid oxidation/gluconeogenesis/ketolysis/-neogenesis, hyperinsulinism) based on patient history
- Diagnosis with any disorder of fatty acid metabolism including Carnitine deficiency (primary), Carnitine palmitoyltransferase (CPT) I or II deficiency, Carnitine translocase deficiency, Beta-oxidation defects, Medium-chain acyl dehydrogenase deficiency (MCAD), Long-chain acyl dehydrogenase deficiency (LCAD), Short-chain acyl dehydrogenase deficiency (SCAD), Long-chain 3-hydroxyacyl-CoA deficiency, Medium-chain 3-hydroxyacyl-CoA deficiency, Pyruvate carboxylase deficiency based on patient history
- Eating disorder based on patient history (as defined by the assessment of the study physician)
- Alcohol abuse based on patient history (as defined by the assessment of the study physician)
- Type 1 diabetes mellitus based on patient history
- Insulin-dependent type 2 diabetes mellitus based on patient history
- Contraindication regarding the MRI exam e.g. non-MRI suitable implants ( including cardiac pacemakers, cochlear implants, aneurysm clip), claustrophobia, large tatoos with metal-containing ink
- Patients, who may be at risk from the blood loss due to scheduled blood draws at the discretion of the physician
- Pregnancy or breastfeeding
- Absence of safe contraceptive measures or non-occurrence of menopause (in women)
- Participation in other interventional trials
- Persons who are in a dependency/employment relationship with the investigators
- Accommodation in an institution by judicial or administrative order.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ketogenic diet
Patients will follow a classical ketogenic diet for 3 month
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Patients will follow a classical ketogenic diet for 3 months
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Experimental: 3-days water-fasting
Patients will perform water fasting on 3 consecutive days within the first 14 days of each of the 3 months.
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Patients will perform water fasting on 3 consecutive days within the first 14 days of each of the 3 months.
In one of the 3 months they are - if required - allowed to split the 3 days into periods of 1 and 2 days.
On all other days of the intervention period they are allowed to eat ad libitum.
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Placebo Comparator: Control
Patients are allowed to eat ad libitum
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Patients are allowed to eat ad libitum, but will be advised that low salt intake (< 5-7 g/day) and sufficient fluid intake (>3 l/day) which is considered beneficial in ADPKD.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Feasibility of ketogenic dietary interventions in every-day life, defined as a combination of objective adherence (ketone body levels) and a patient-reported feasibility questionnaire
Time Frame: Day 90
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Day 90
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Between group-difference of the relative change in Total kidney volume
Time Frame: baseline and day 90
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Measured by abdominal MRI (segmentation) at screening visit and after the dietary intervention (visit 5).
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baseline and day 90
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Between group-difference of the relative change in Body-Mass-Index (BMI)
Time Frame: baseline and day 90
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Determination of BMI before and after dietary intervention
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baseline and day 90
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Between group-difference of the relative change of insulin sensitivity
Time Frame: baseline and day 90
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Measurement of insulin-like growth factor (IGF 1), insulin and C-peptide in blood samples (measurement unit µg/l) before and after dietary intervention
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baseline and day 90
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Between group-difference in hsCRP
Time Frame: baseline and day 90
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Measurement of high-sensitive CRP (hsCRP) in blood samples before and after dietary intervention
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baseline and day 90
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Change in quality of life assessed using the Short Form (12) Health Survey (SF-12) before and after the dietary intervention
Time Frame: Baseline and day 90
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Patients will complete a standardized quality of life questionnaire (QoL, SF-12) before and after the dietary intervention (higher values indicate better QoL, ranging from 0-100)
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Baseline and day 90
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Change in health-related quality of life assessed using the ADPKD-impact scale before and after the dietary intervention
Time Frame: Baseline and day 90
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Patients will complete a standardized health-related quality of life questionnaire (ADPKD-impact scale) before and after the dietary intervention (lower values indicate better HRQoL, ranging from 1-5)
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Baseline and day 90
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Between group-difference in blood pressure
Time Frame: Baseline and day 90
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Measurement of systolic and diastolic blood pressure before and after dietary intervention
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Baseline and day 90
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Incidence of Diet-related Emergent Adverse Events [Safety] at day 30, day 60, day 90 and day 120
Time Frame: Day 30, day 60, day 90, day 120
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Occurence if Diet-related emergent adverse events will be assessed using lab values (GOT/GPT ≥ 3 times upper limit of normal, increase in serum creatinine fulfilling the KDIGO AKI criteria, triglycerides > 800 mg/dl) and incidence of renal complications (macrohematuria, flank pain, cyst infection, nephrolithiasis)
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Day 30, day 60, day 90, day 120
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Roman-Ulrich Müller, Prof., Department II of Internal Medicine, University of Cologne
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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