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

NCT04680780 | Completed

• 1 other identifier: 02
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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

Conditions

ADPKD

Keywords

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

Outcome Measures

Primary Outcomes (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

  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.

  Day 90

Secondary Outcomes (8)

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

  baseline and day 90

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

  baseline and day 90

• Between group-difference of the relative change of insulin sensitivity

  baseline and day 90

• Between group-difference in hsCRP

  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

  Baseline and day 90

Study Arms (3)

Ketogenic diet

EXPERIMENTAL

Patients will follow a classical ketogenic diet for 3 month

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.

Other: 3-days water-fasting

Control

PLACEBO COMPARATOR

Patients are allowed to eat ad libitum

Other: Control

Interventions

Ketogenic diet OTHER

Patients will follow a classical ketogenic diet for 3 months

Ketogenic diet

3-days water-fasting OTHER

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.

3-days water-fasting

Control OTHER

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.

Control

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Cologne: lead

Study Sites (1)

Department II of Internal Medicine, University Hospital of Cologne

Cologne, 50937, Germany

Location

Related Publications (2)

• 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.

  PMID: 39356039 DERIVED

• Cukoski 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.

  PMID: 37935200 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Ketosis; Fasting

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Roman-Ulrich Müller, Prof.

  Department II of Internal Medicine, University of Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department II of Internal Medicine

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: December 23, 2020
• Study Start: January 10, 2021
• Primary Completion: August 12, 2022
• Study Completion: August 12, 2022
• Last Updated: August 24, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)