Clinical trial NCT04680780: Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Official title: Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ADPKD
Keywords: ADPKD
Ketosis
dietary intervention
ketogenic diet
3-days water fasting
fasting
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2020-12-23
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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:

1. Feasibility: Are ketogenic dietary interventions acceptable to ADPKD patients in everyday life?
2. Safety: Are there adverse events of ketogenic dietary interventions in ADPKD patients?
3. Efficacy: Do the dietary interventions reach the metabolic endpoints? Do they have a short-term impact on kidney volume?
4. 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)


Eligibility criteria: Inclusion Criteria:

1. Male and female ADPKD patients (based on genetics or imaging) ≥ 18 and ≤ 60 years
2. 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)
3. CKD-stages G1-3 as determined by eGFR (CKD-EPI)
4. Written informed consent

Exclusion Criteria:

1. Underweight or obese individuals ( as defined by BMI ≤ 18.5 kg/m2 or ≥ 35 kg/m2)
2. Exposure to a ketogenic diet (classical ketogenic diet or modified Atkins)for more than 2 weeks within the last 6 months
3. Participation in a weight-loss program within the last 6 months based on patient history
4. Vegetarian / vegan lifestyle based on patient history
5. Current treatment (or within the last 6 months) with tolvaptan or a somatostatin analogue based on patient history
6. Inability to give informed consent
7. 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
8. 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
9. Eating disorder based on patient history (as defined by the assessment of the study physician)
10. Alcohol abuse based on patient history (as defined by the assessment of the study physician)
11. Type 1 diabetes mellitus based on patient history
12. Insulin-dependent type 2 diabetes mellitus based on patient history
13. 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
14. Patients, who may be at risk from the blood loss due to scheduled blood draws at the discretion of the physician
15. Pregnancy or breastfeeding
16. Absence of safe contraceptive measures or non-occurrence of menopause (in women)
17. Participation in other interventional trials
18. Persons who are in a dependency/employment relationship with the investigators
19. Accommodation in an institution by judicial or administrative order.

Primary outcomes:
measure: 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
timeFrame: Day 90
Secondary outcomes:
measure: Between group-difference of the relative change in Total kidney volume
timeFrame: baseline and day 90
measure: Between group-difference of the relative change in Body-Mass-Index (BMI)
timeFrame: baseline and day 90
measure: Between group-difference of the relative change of insulin sensitivity
timeFrame: baseline and day 90
measure: Between group-difference in hsCRP
timeFrame: baseline and day 90
measure: Change in quality of life assessed using the Short Form (12) Health Survey (SF-12) before and after the dietary intervention
timeFrame: Baseline and day 90
measure: Change in health-related quality of life assessed using the ADPKD-impact scale before and after the dietary intervention
timeFrame: Baseline and day 90
measure: Between group-difference in blood pressure
timeFrame: Baseline and day 90
measure: Incidence of Diet-related Emergent Adverse Events [Safety] at day 30, day 60, day 90 and day 120
timeFrame: Day 30, day 60, day 90, day 120
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Department II of Internal Medicine, University Hospital of Cologne
Study officials:
affiliation: Department II of Internal Medicine, University of Cologne
name: Roman-Ulrich Müller, Prof.
role: PRINCIPAL_INVESTIGATOR
References: