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

Primary Purpose

ADPKD

Status

Completed

Phase

Not Applicable

Locations

Germany

Study Type

Interventional

Intervention

Ketogenic diet

3-days water-fasting

Control

About this trial

This is an interventional other trial for ADPKD focused on measuring ADPKD, Ketosis, dietary intervention, ketogenic diet, 3-days water fasting, fasting

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Department II of Internal Medicine, University Hospital of Cologne

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Ketogenic diet

3-days water-fasting

Control

Arm Description

Patients will follow a classical ketogenic diet for 3 month

Patients will perform water fasting on 3 consecutive days within the first 14 days of each of the 3 months.

Patients are allowed to eat ad libitum

Outcomes

Primary Outcome Measures

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

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.

Secondary Outcome Measures

Between group-difference of the relative change in Total kidney volume

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)

Determination of BMI before and after dietary intervention

Between group-difference of the relative change of insulin sensitivity

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

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

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

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

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

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)

Full Information

NCT ID

NCT04680780

First Posted

October 1, 2020

Last Updated

August 23, 2022

Sponsor

University of Cologne

1. Study Identification

Unique Protocol Identification Number

NCT04680780

Brief Title

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

Acronym

Keto-ADPKD

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

January 10, 2021 (Actual)

Primary Completion Date

August 12, 2022 (Actual)

Study Completion Date

August 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Cologne

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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: 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

ADPKD

Keywords

ADPKD, Ketosis, dietary intervention, ketogenic diet, 3-days water fasting, fasting

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

63 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ketogenic diet

Arm Type

Experimental

Arm Description

Patients will follow a classical ketogenic diet for 3 month

Arm Title

3-days water-fasting

Arm Type

Experimental

Arm Description

Patients will perform water fasting on 3 consecutive days within the first 14 days of each of the 3 months.

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

Patients are allowed to eat ad libitum

Intervention Type

Other

Intervention Name(s)

Ketogenic diet

Intervention Description

Patients will follow a classical ketogenic diet for 3 months

Intervention Type

Other

Intervention Name(s)

3-days water-fasting

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Control

Intervention Description

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 Measure Information:

Title

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

Description

Time Frame

Day 90

Secondary Outcome Measure Information:

Title

Between group-difference of the relative change in Total kidney volume

Description

Measured by abdominal MRI (segmentation) at screening visit and after the dietary intervention (visit 5).

Time Frame

baseline and day 90

Title

Between group-difference of the relative change in Body-Mass-Index (BMI)

Description

Determination of BMI before and after dietary intervention

Time Frame

baseline and day 90

Title

Between group-difference of the relative change of insulin sensitivity

Description

Measurement of insulin-like growth factor (IGF 1), insulin and C-peptide in blood samples (measurement unit µg/l) before and after dietary intervention

Time Frame

baseline and day 90

Title

Between group-difference in hsCRP

Description

Measurement of high-sensitive CRP (hsCRP) in blood samples before and after dietary intervention

Time Frame

baseline and day 90

Title

Change in quality of life assessed using the Short Form (12) Health Survey (SF-12) before and after the dietary intervention

Description

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)

Time Frame

Baseline and day 90

Title

Change in health-related quality of life assessed using the ADPKD-impact scale before and after the dietary intervention

Description

Time Frame

Baseline and day 90

Title

Between group-difference in blood pressure

Description

Measurement of systolic and diastolic blood pressure before and after dietary intervention

Time Frame

Baseline and day 90

Title

Incidence of Diet-related Emergent Adverse Events [Safety] at day 30, day 60, day 90 and day 120

Description

Time Frame

Day 30, day 60, day 90, day 120

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Roman-Ulrich Müller, Prof.

Organizational Affiliation

Department II of Internal Medicine, University of Cologne

Official's Role

Principal Investigator

Facility Information:

Facility Name

Department II of Internal Medicine, University Hospital of Cologne

City

Cologne

ZIP/Postal Code

50937

Country

Germany

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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