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Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (Keto-ADPKD)

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ClinicalTrials.gov Identifier: NCT04680780
Recruitment Status : Recruiting
First Posted : December 23, 2020
Last Update Posted : January 13, 2021
Sponsor:
Information provided by (Responsible Party):
Roman Müller, University of Cologne

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)


Condition or disease Intervention/treatment Phase
ADPKD Other: Ketogenic diet Other: 3-days water-fasting Other: Control Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Actual Study Start Date : January 10, 2021
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : May 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arm Intervention/treatment
Experimental: Ketogenic diet
Patients will follow a classical ketogenic diet for 3 month
Other: Ketogenic diet
Patients will follow a classical ketogenic diet for 3 months

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.
Other: 3-days water-fasting
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.

Placebo Comparator: Control
Patients are allowed to eat ad libitum
Other: Control
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.




Primary Outcome Measures :
  1. 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 ]
    1. Adherence: (A) Ketogenic diet-group: (1) ketone body levels ≥0.8 mmol/l in ≥75% of blood measurements at visits/patient or (2) ≥10 ppm in ≥75 % of Breathalyzer measurements and ketone body levels ≥0.8 mmol/l in ≥50% of blood measurements at visits/patient, to be reached by ≥ 75% of the participants by ≥50% of all per protocol measurements (B) 3-day water-fasting group:(1) full compliance to diet on ≥75% days/patient (based on diary), to be reached by ≥75% of the participants or by ≥50% of all per protocol measurements (2) at least 1 ketone body level ≥10 ppm/day on at least 2 out of 3 days of each fasting phase (analyzed using breathalyzer).
    2. Patient-reported feasibility will be measured using a dedicated feasibility questionnaire by counting the answers to the questions 1-17 and 21-26 (options ranging from-4 to+4 with higher values indicating better feasibility). Goal: Average value ≥0 in at least 75% of the participants.Both targets have to be met to reach the primary endpoint.


Secondary Outcome Measures :
  1. Between group-difference of the relative change in Total kidney volume [ Time Frame: baseline and day 90 ]
    Measured by abdominal MRI (segmentation) at screening visit and after the dietary intervention (visit 5).

  2. Between group-difference of the relative change in Body-Mass-Index (BMI) [ Time Frame: baseline and day 90 ]
    Determination of BMI before and after dietary intervention

  3. Between group-difference of the relative change of insulin sensitivity [ Time Frame: baseline and day 90 ]
    Measurement of insulin-like growth factor (IGF 1), insulin and C-peptide in blood samples (measurement unit µg/l) before and after dietary intervention

  4. Between group-difference in hsCRP [ Time Frame: baseline and day 90 ]
    Measurement of high-sensitive CRP (hsCRP) in blood samples before and after dietary intervention

  5. 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 ]
    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)

  6. 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 ]
    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)

  7. Between group-difference in blood pressure [ Time Frame: Baseline and day 90 ]
    Measurement of systolic and diastolic blood pressure before and after dietary intervention

  8. 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 ]
    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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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04680780


Contacts
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Contact: Roman-Ulrich Müller, Prof. +49 221 478 97222 roman-ulrich.mueller@uk-koeln.de
Contact: Franziska Grundmann, MD +49 221 478 97222 franziska.grundmann@uk-koeln.de

Locations
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Germany
Department II of Internal Medicine, University Hospital of Cologne Recruiting
Cologne, Germany, 50937
Contact: Roman-Ulrich Mueller, Prof.       roman-ulrich.mueller@uk-koeln.de   
University Hospital of Cologne Recruiting
Cologne, Germany, 50937
Contact: Roman-Ulrich Müller, Prof.    + 49 221 478 97222    roman-ulrich.mueller@uk-koeln.de   
Contact: Franziska Grundmann, MD    + 49 221 478 97222    franziska.grundmann@uk-koeln.de   
Sponsors and Collaborators
University of Cologne
Investigators
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Principal Investigator: Roman-Ulrich Müller, Prof. Department II of Internal Medicine, University of Cologne
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Responsible Party: Roman Müller, Department II of Internal Medicine, University of Cologne
ClinicalTrials.gov Identifier: NCT04680780    
Other Study ID Numbers: 02
First Posted: December 23, 2020    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Roman Müller, University of Cologne:
ADPKD
Ketosis
dietary intervention
ketogenic diet
3-days water fasting
fasting
Additional relevant MeSH terms:
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Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic
Abnormalities, Multiple
Congenital Abnormalities
Ciliopathies
Genetic Diseases, Inborn