ADPKDKeto-ADPKDNCT04680780
Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
A study testing Ketogenic diet and 3-days water-fasting in people with ADPKD, run by University of Cologne at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- ADPKD
- What is being tested?
- Ketogenic diet and 3-days water-fasting
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 1 siteGermany
- Study dates
- 10 Jan 2021to 12 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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),
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department II of Internal Medicine, University Hospital of Cologne
Cologne, 50937
About this study
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:
Read more
- 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:
- Ketogenic diet B) 3-day water fasting C) Control: ad libitum food intake (no diet)
- Conditions
- ADPKD
- Being tested
- Ketogenic diet, 3-days water-fasting, Control
- Keywords
- ADPKD, Ketosis, dietary intervention, ketogenic diet, 3-days water fasting, fasting
- Medical subject headings
- Polycystic Kidney, Autosomal Dominant, Ketosis, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic dietOther
Patients will follow a classical ketogenic diet for 3 months
3-days water-fastingOther
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.
ControlOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic diet | Experimental | Patients will follow a classical ketogenic diet for 3 month Receives: Other: Ketogenic diet |
| 3-days water-fasting | Experimental | Patients will perform water fasting on 3 consecutive days within the first 14 days of each of the 3 months. Receives: Other: 3-days water-fasting |
| Control | Placebo comparator | Patients are allowed to eat ad libitum Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 90
Secondary outcomes (8)
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).
Measured: baseline and day 90
Between group-difference of the relative change in Body-Mass-Index (BMI)
Determination of BMI before and after dietary intervention
Measured: baseline and day 90
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
Measured: baseline and day 90
Between group-difference in hsCRP
Measurement of high-sensitive CRP (hsCRP) in blood samples before and after dietary intervention
Measured: baseline and day 90
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)
Measured: Baseline and day 90
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)
Measured: Baseline and day 90
Between group-difference in blood pressure
Measurement of systolic and diastolic blood pressure before and after dietary intervention
Measured: Baseline and day 90
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)
Measured: Day 30, day 60, day 90, day 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2020
- Study start10 Jan 2021
- Primary completion12 Aug 2022
- Study completion12 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for ADPKDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cologne
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roman Müller, University of Cologne
- Investigators
- Roman-Ulrich Müller, Prof., Principal investigator, Department II of Internal Medicine, University of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04680780
- Sponsor's protocol ID
- 02
- Acronym
- Keto-ADPKD
- Status last verified
- Aug 2022
- First submitted
- 1 Oct 2020
- Last updated
- 24 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039Cukoski S, Lindemann CH, Arjune S, Todorova P, Brecht T, Kuhn A, Oehm S, Strubl S, Becker I, Kammerer U, Torres JA, Meyer F, Schomig T, Hokamp NG, Siedek F, Gottschalk I, Benzing T, Schmidt J, Antczak P, Weimbs T, Grundmann F, Muller RU. Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial. Cell Rep Med. 2023 Nov 21;4(11):101283. doi: 10.1016/j.xcrm.2023.101283. Epub 2023 Nov 7.
PubMed 37935200
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketogenic Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- ClinicalTrials.gov ID
- NCT04680780
- Acronym / sponsor ID
- Keto-ADPKD / 02
- Conditions
- ADPKD
- Keywords
- ADPKD, Ketosis, dietary intervention, ketogenic diet, 3-days water fasting, fasting
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- University of CologneUniversity, hospital or other
- Study start
- 10 Jan 2021 (actual)
- Primary completion
- 12 Aug 2022 (actual)
- Study completion
- 12 Aug 2022 (actual)
- First posted
- 23 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Ketogenic diet B) 3-day water fasting C) Control: ad libitum food intake (no diet)
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ketogenic diet | Experimental | Other: Ketogenic dietPatients will follow a classical ketogenic diet for 3 month |
| 3-days water-fasting | Experimental | Other: 3-days water-fastingPatients will perform water fasting on 3 consecutive days within the first 14 days of each of the 3 months. |
| Control | Placebo comparator | Other: ControlPatients are allowed to eat ad libitum |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Male and female ADPKD patients (based on genetics or imaging) ≥ 18 and ≤ 60 years
- Indicators of rapid progression, either of the following:
- CKD-stages G1-3 as determined by eGFR (CKD-EPI)
- Written informed consent
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketogenic dietPatients will follow a classical ketogenic diet for 3 months | Other | Ketogenic diet |
| 3-days water-fastingPatients 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. | Other | 3-days water-fasting |
| ControlPatients 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. | Other | Control |
Primary outcome
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.
8 secondary outcomes
Between group-difference of the relative change in Total kidney volume
Time frame: baseline and day 90
Between group-difference of the relative change in Body-Mass-Index (BMI)
Time frame: baseline and day 90
Between group-difference of the relative change of insulin sensitivity
Time frame: baseline and day 90
Between group-difference in hsCRP
Time frame: baseline and day 90
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
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
Between group-difference in blood pressure
Time frame: Baseline and day 90
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2022.
- Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
- Derived from this study: PubMed 37935200Cukoski S, Lindemann CH, Arjune S, Todorova P, Brecht T, Kuhn A, Oehm S, Strubl S, Becker I, Kammerer U, Torres JA, Meyer F, Schomig T, Hokamp NG, Siedek F, Gottschalk I, Benzing T, Schmidt J, Antczak P, Weimbs T, Grundmann F, Muller RU. Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial. Cell Rep Med. 2023 Nov 21;4(11):101283. doi: 10.1016/j.xcrm.2023.101283. Epub 2023 Nov 7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roman-Ulrich Müller, Prof. principal investigator
Department II of Internal Medicine, University of Cologne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketogenic diet and 3-days water-fasting in people with ADPKD, run by University of Cologne at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Day 90). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04680780, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2022.