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
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)
|Condition or disease||Intervention/treatment||Phase|
|ADPKD||Other: Ketogenic diet Other: 3-days water-fasting Other: Control||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||63 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
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
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.
- 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 ]
- 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).
- 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.
- 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).
- 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
- 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
- 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
- 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)
- 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)
- Between group-difference in blood pressure [ Time Frame: Baseline and day 90 ]Measurement of systolic and diastolic blood pressure before and after dietary intervention
- 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)
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
|Contact: Roman-Ulrich Müller, Prof.||+49 221 478 firstname.lastname@example.org|
|Contact: Franziska Grundmann, MD||+49 221 478 email@example.com|
|Department II of Internal Medicine, University Hospital of Cologne||Recruiting|
|Cologne, Germany, 50937|
|Contact: Roman-Ulrich Mueller, Prof. firstname.lastname@example.org|
|University Hospital of Cologne||Recruiting|
|Cologne, Germany, 50937|
|Contact: Roman-Ulrich Müller, Prof. + 49 221 478 97222 email@example.com|
|Contact: Franziska Grundmann, MD + 49 221 478 97222 firstname.lastname@example.org|
|Principal Investigator:||Roman-Ulrich Müller, Prof.||Department II of Internal Medicine, University of Cologne|