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Short Term Induction of Ketosis in PKD (RESET-PKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04472624
Recruitment Status : Recruiting
First Posted : July 15, 2020
Last Update Posted : July 15, 2020
Sponsor:
Information provided by (Responsible Party):
Roman Müller, University of Cologne

Brief Summary:
Recently, it has been shown that ketose-inducing dietary interventions slow disease progression in animal models of polycystic kidney disease (PKD), even when the state of ketosis is only induced for a short period of time. The present study aims to investigate the effects of short term ketosis on total kidney volume (TKV) (and other parameters) in 10 ADPKD-patients with rapidly progressive disease.

Condition or disease Intervention/treatment Phase
ADPKD Other: Fasting Other: Ketogenic diet Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Short Term Induction of Ketosis in PKD
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : July 14, 2021
Estimated Study Completion Date : October 17, 2021

Arm Intervention/treatment
Experimental: Fasting arm
Participants will be fasting during 72 hours
Other: Fasting
Acute fasting for 72 hours

Experimental: Diet arm
Participants will be using ketogenic diet for 14 days
Other: Ketogenic diet
Intake of a ketogenic diet for 14 days




Primary Outcome Measures :
  1. Relative difference of TKV immediately before and after the ketonic state [ Time Frame: Visit 2: 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2 ]
    MRI-based kidney volumetry at study visit 2 and study visit 3


Secondary Outcome Measures :
  1. Absolute and relative difference of TKV [ Time Frame: Baseline visit (V1) and final study visit (V4) after at maximum 95 days ]
    assessed by MRI-based volumetry at all study visits

  2. Absolute and relative difference of height-adjusted total kidney volume (htTKV) [ Time Frame: Baseline visit (V1) and final study visit (V4) after at maximum 95 days ]
    assessed by MRI-based volumetry at all study visits

  3. Absolute and relative difference of total liver volume (TLV) [ Time Frame: Baseline visit (V1) and final study visit (V4) after at maximum 95 days ]
    assessed by MRI-based volumetry at all study visits

  4. Absolute and relative difference of cystic burden of kidneys and liver [ Time Frame: Baseline visit (V1) and final study visit (V4) after at maximum 95 days ]
    assessed by MRI at all study visits

  5. Absolute and relative change of Renal Function Panel [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement of creatinine, urea and uric acid in blood and urine samples (measurement unit mg/dl)

  6. Absolute and relative change of electrolytes and minerals [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement of electrolyte and minerals (sodium, natrium, potassium, magnesium, chloride, phosphate) in blood (measurement unit mmol/L) and urine samples (measurement unit mmol/24h)

  7. Absolute and relative change of albumin [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement in blood and urine samples

  8. Absolute and relative change of glucose [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement in blood and urine samples

  9. Absolute and relative change of Hepatic Function Panel [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement of Alanine aminotransferase(ALT), Aspartate Aminotransferase (ASP), Alkaline Phosphatase (ALP), gamma-glutamyl transferase (GGT) and Lactate Dehydrogenase (LD) in blood samples (measurement unit U/L)

  10. Absolute and relative change of bilirubin [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement in blood samples

  11. Absolute and relative change of lipid panel [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement of high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol, triglycerides and lipoprotein(a) in blood samples

  12. Absolute and relative change of inflammatory parameters [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement of c-reactive protein (CRP) and high sensitivity c-reactive protein (hsCRP) in blood samples ( measurement unit mg/L)

  13. Absolute and relative change in blood count [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement of white blood cells, red blood cells, platelets in blood samples (measurement unit 10^9/L )

  14. Absolute and relative change of hemoglobin [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement in blood samples

  15. Absolute and relative change of hematokrit [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement in blood samples

  16. Absolute and relative change of betahydroxybutyrate level [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement of betahydroxybutyrate level in blood samples for determination of ketosis

  17. Absolute and relative change in blood gas analysis [ Time Frame: Baseline visit (V1), study visit 2 (V2): 2-4 Weeks after enrolment; Visit 3: 3 - 21 days after Visit 2, and final study visit (V4) after at maximum 95 days ]
    Measurement with blood gas analyzer for determination of ketosis

  18. Analysis of the ketonic state with betahydroxybutyrate level [ Time Frame: Baseline visit (V1), during 14 days of ketogenic diet or 3 days fasting and final study visit (V4) after at maximum 95 days ]
    Betahydroxybutyrate measurement from blood samples of the fingertip by patients at home

  19. Analysis of the ketonic state with ketonuria [ Time Frame: Baseline visit (V1), during 14 days of ketogenic diet or 3 days fasting and final study visit (V4) after at maximum 95 days ]
    Ketonuria measured with urine stix by patients at home

  20. Analysis of the ketonic state with acetoacetate in breath [ Time Frame: Baseline visit (V1), during 14 days of ketogenic diet or 3 days fasting and final study visit (V4) after at maximum 95 days ]
    determination of acetoacetate in breath by patients at home

  21. Absolute and relative change of height [ Time Frame: Baseline visit (V1), V2 (2-4 Weeks after enrolment); Visit 3 (3 - 21 days after Visit 2 ) and final study visit (V4) after at maximum 95 days ]
    Determination of height

  22. Absolute and relative change of weight [ Time Frame: Baseline visit (V1), V2 (2-4 Weeks after enrolment); Visit 3 (3 - 21 days after Visit 2 ) and final study visit (V4) after at maximum 95 days ]
    Determination of weight

  23. Absolute and relative change of waist circumference [ Time Frame: Baseline visit (V1), V2 (2-4 Weeks after enrolment); Visit 3 (3 - 21 days after Visit 2 ) and final study visit (V4) after at maximum 95 days ]
    Determination of waist circumference

  24. Relative change of calorimetry [ Time Frame: Baseline visit (V1), V2 (2-4 Weeks after enrolment); Visit 3 (3 - 21 days after Visit 2 ) and final study visit (V4) after at maximum 95 days ]
    Could be determined instead of anthropometric parameters

  25. Changes in Bioimpedance [ Time Frame: Baseline visit (V1), V2 (2-4 Weeks after enrolment); Visit 3 (3 - 21 days after Visit 2 ) and final study visit (V4) after at maximum 95 days ]
    Bioimpedance measurements on each visit

  26. Feeling of hunger, discomforts and problems [ Time Frame: In between baseline visit (V1) and final study visit (V4) after at maximum 95 days ]
    measured and documented at home in a study dietary in between study visits

  27. Acetoacetate-concentrations [ Time Frame: In between baseline visit (V1) and final study visit (V4) after at maximum 95 days ]
    measured and documented at home in a study dietary in between study visits


Other Outcome Measures:
  1. Changes of renal functional panel in 24-h-urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention for the determination of creatinine, uric acid and urea (measurement unit mg/24h)

  2. Changes of electrolytes and minerals in 24-h-urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention for the determination of sodium, natrium, potassium, magnesium, chloride, phosphate (measurement unit mmol/24h )

  3. Changes of glucose in 24-h-urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention

  4. Changes of albumin in 24-h-urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention

  5. Analysis of stool samples [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Stool samples will be collected before and during the dietary intervention and analysed

  6. Changes of renal functional panel in spot urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention for the determination of creatinine, uric acid and urea (measurement unit g/24h)

  7. Changes of electrolytes and minerals in spot urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention for the determination of sodium, natrium, potassium, magnesium, chloride, phosphate (measurement unit mmol/24h)

  8. Changes of albumin in spot urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention

  9. Changes of glucose in spot urine [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention

  10. Changes in urinary doubly refractile lipid bodies [ Time Frame: Baseline and during 14 days of ketogenic diet or 3 days fasting ]
    Urin samples will be collected before and during the dietary intervention



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Male and female ADPKD-patients (diagnosed by genetics / typical MRI / ultrasound)
  • With evidence of fast progression, at least one of the following criteria

    1. Mayo Class 1C-1E
    2. Truncating PKD1-mutation
    3. Hypertension < 35 years
    4. Urological complications < 35 years
    5. ≥ 1 first class or second class family member with need of renal replacement therapy < 60 years
    6. eGFR loss > 2,5 ml/min/1,73m2 per year
    7. PROPKD-Score > 6
  • Age ≥ 18 and ≤ 60 years
  • CKD stage 1-3a according to eGFR
  • Signed written informed consent

Exclusion Criteria:

  • Currently under tolvaptan
  • BMI < 18 or > 35
  • Diabetes mellitus (Type I, Type II, MODY, LADA)
  • Active alcoholism
  • Vegan or vegetarian lifestyle
  • Inability to sign or understand written informed consent
  • Anamnestically known circumstances which forbid the induction of a ketonic state by ketogenic diet or acute fasting (Liver damage (AST/ALT > 3x upper limit of normal, alkaline phosphatase > 6x upper limit of normal , Bilirubin ≥ 3 mg/dl), Diabetes mellitus, Pyruvate carboxylase deficiency, defects of gluconeogenesis, defects of ketolysis / ketogenesis, hyperinsulinism, defects of fatty acid oxidation )
  • Allergies or food intolerance against components of a ketogenic diet
  • Eating disorders (Anorexia nervosa / Bulimia)
  • Participation in a weight loss program (e.g. Optifast) or intake of medication to promote weight loss within the last six months
  • Ketogenic Diet > 1 month within the last 12 months
  • Chronic renal replacement therapy
  • Previous history of kidney transplantation
  • Uncontrolled local or systemic infection (according to clinical assessment)
  • Simultaneous participation in other interventional studies
  • Pregnant or breastfeeding women
  • Persons who are dependent of or employed by the study investigators
  • Contraindications against MRI examinations (stents, pacemakers or other metal inserts, claustrophobia)
  • Persons living in an establishment by court order or official instructions

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): NCT04472624


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

Locations
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Germany
Department II of Internal Medicine, University Hospital Cologne Recruiting
Cologne, Germany, 50937
Contact: Roman-Ulrich Mueller, Prof.       roman-ulrich.mueller@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
Additional Information:
Publications:
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Responsible Party: Roman Müller, Department II of Internal Medicine, University of Cologne
ClinicalTrials.gov Identifier: NCT04472624    
Other Study ID Numbers: 20-1040
First Posted: July 15, 2020    Key Record Dates
Last Update Posted: July 15, 2020
Last Verified: July 2020
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
dietary intervention
ketosis
fasting
ketogenic diet
Additional relevant MeSH terms:
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Ketosis
Acidosis
Acid-Base Imbalance
Metabolic Diseases