Pravastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease

Related Clinical Trial
IMPEDE-PKD Randomised Placebo-controlled Trial Daily Caloric Restriction in ADPKD To Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AL01211 in Healthy Volunteers and Autosomal Dominant Polycystic Kidney Disease Subjects Establishment of the Human Intestinal and Salivary Microbiota Biobank – Kidney Diseases NOX4 and Related Biomarkers in ADPKD A Study to Evaluate the Effects of GLPG2737 in Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD) An Extended Access Program for Bardoxolone Methyl in Patients With CKD (EAGLE) PErfusioN, OxyGen ConsUmptIon and ENergetics in ADPKD (PENGUIN) PKD Biomarkers Study Sirolimus for Massive Polycystic Liver Wishing to Decrease Aquaresis in ADPKD Patients Treated With a V2Ra; the Effect of Regulating Protein and Salt The German ADPKD Tolvaptan Treatment Registry A New Diet for Patients With Autosomal Dominant Polycystic Disease (ADPKD) Statin Therapy in Patients With Early Stage ADPKD Evaluation of Iliac and Renal Artery for Mechanism of Intracranial Aneurysm in ADPKD A Phase 2 Trial of the Safety and Efficacy of Bardoxolone Methyl in Patients With Rare Chronic Kidney Diseases – PHOENIX PKD Clinical and Translational Core Study Dynamic Measurement of Renal Functional Reserve as a Predictor of Long-Term Renal Function Mesenchymal Stem Cells Transplantation in Patients With Chronic Renal Failure Due to Polycystic Kidney Disease Renal Sympathetic Denervation for Reduction of Pain and Improvement of Insulin Sensitivity in Adult Polycystic Kidney Disease Evaluation of Nephrectomy Specimen for Intracranial Aneurysm Development in ADPKD Lanreotide In Polycystic Kidney Disease Study Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease Dietary Intervention in ADPKD on Tolvaptan High Water Intake in Polycystic Kidney Disease Efficacy and Safety of Lixivaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease Long-Term Treatment and Follow up of Subjects Completing 24 Months of Treatment With Tesevatinib on Study KD019-101 Safety of Lixivaptan in Subjects Previously Treated With Tolvaptan for Autosomal Dominant Polycystic Kidney Disease A Trial of Bardoxolone Methyl in Patients With ADPKD – FALCON Study of the Efficacy and Safety of Tesevatinib in Subjects With ADPKD Tolvaptan-Octreotide LAR Combination in ADPKD Polycystic Kidney Disease Data Repository ADPKD Patient Registry Use of Low Dose Pioglitazone to Treat Autosomal Dominant Polycystic Kidney Disease ADPKD Cohort Study Dose-finding Study of New Tolvaptan Formulation in Subjects With ADPKD Canadian Medical Assessment of JINARC™ Outcomes Registry Analysis of Clinical and Molecular Genetic Data Influencing the Evolution and Response to Therapy of ADPKD Patients (Autosomal Dominant Polycystic Kidney Disease) ADPKD Alterations in Hepatic Transporter Function Efficacy Study of Water Drinking on PKD Progression. A Study Measuring Quality of Life, Treatment Preference and Satisfaction of ADPKD Patients in Europe Somatostatin in Polycystic Kidney: a Long-term Three Year Follow up Study Open-Label Tolvaptan Study in Subjects With ADPKD Effects of Somatostatin on ADPKD Heart Clinical and Molecular Description of PKD1 and PKD2 Mutation Negative Carriers in ADPKD Diet as a Potential Treatment for Autosomal Dominant Polycystic Kidney Disease Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD): The Role of Biomarkers in Predicting a Response to Therapy Effect of the Aquaretic Tolvaptan on Nitric Oxide System Pilot Study of Rapamycin as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD) Outcome of Autosomal Dominant Polycystic Kidney Disease Patients on Peritoneal Dialysis: a National Retrospective Study Based on Two French Registries (the French Language Peritoneal Dialysis Registry and the French Renal Epidemiology and Information Network). Clinical Implications of DNA Analysis on ADPKD The Efficacy of Everolimus in Reducing Total Native Kidney Volume in Polycystic Kidney Disease Transplanted Recipients Subacute Effect of Tolvaptan on Total Kidney Volume in Adult Patients With Autosomal Dominant Polycystic Kidney Disease Assessment of Longitudinal Changes in Endothelial Function and Oxidative Stress in Normotensive Patients With ADPKD The Eurocyst Initiative: Building a Network of ADPKD Reference Centers Across Europe Efficacy of Tolvaptan on ADPKD Patients Pravastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Study 156-04-001] A Long-term Administration Study of OPC-41061 in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) (2) [Extension of Study 156-05-002] Somatostatin In Patients With Autosomal Dominant Polycystic Kidney Disease And Moderate To Severe Renal Insufficiency ADPKD and Peritoneal Dialysis: How Anticipate Peritoneal Pressure? Triptolide-Containing Formulation as Treatment for Autosomal Dominant Polycystic Kidney Disease (ADPKD) Observational Study in Patients With Autosomal Dominant Polycystic Kidney Disease Evaluating the Safety and effectivenesS in Adult KorEaN Patients Treated With Tolvaptan for Management of Autosomal domInAnt poLycystic Kidney Disease A Study to Investigate the Long-term Safety and Efficacy of Tolvaptan in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD) [Extension of Trial 156-04-251 in Japan] Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease The ELiSA Study – Evaluation of Lixivaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease Short-term Renal Hemodynamic Effects of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD) Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) New Quantitive MRI Parameters in Assessing Kidneys of Autosomal Dominant Polycystic Kidney Disease Autosomal Dominant Polycystic Kidney Disease Somatic Mutation Biorepository Sirolimus (Rapamune®) for Autosomal Dominant Polycystic Kidney Disease (ADPKD) A Clinical Trial of Water Therapy for Autosomal Dominant Polycystic Kidney Disease Adrenal Functions in Autosomal Dominant Polycystic Kidney Disease Repository Study of Autosomal Dominant Polycystic Kidney Disease Sirolimus In Autosomal Dominant Polycystic Kidney Disease And Severe Renal Insufficiency Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease The Safety and Efficacy of Catheter-based Renal Denervation Using the Vessix™ Renal Denervation System in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Patients With Severe Debilitating Pain Water as Therapy in Autosomal Dominant Polycystic Kidney Disease (ADPKD) 8-Week Study of Tolvaptan Dose Forms in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Characterization of the Nrf2 Response in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Brief Title

Pravastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease

Official Title

Pravastatin and Alkali Therapy in Patients With Autosomal Dominant Polycystic Kidney Disease

Brief Summary

      This is an one-year open-label study to determine treatment efficacy and feasibility of a
      trial that uses open-label interventions in ADPKD patients.
    

Detailed Description

      Polycystic Kidney Disease (PKD) is the most common genetic disease leading to End Stage
      Kidney Disease (ESKD), affecting between 1 in 500-1000 individuals from every ethnic group.
      The autosomal dominant (ADPKD) form arises from a two-hit downregulation of proteins encoded
      by either PKD1 or PKD2. Although many potential therapies have been studied to slow
      progression of ADPKD, none to date have been proven to be both safe and effective in slowing
      disease progression. Cholesterol-lowering agents called statins have shown promise in the
      treatment of younger ADPKD patients, reducing inflammation and progression as assessed by
      kidney growth, but their utility appears to be limited in older populations and those with
      more advanced chronic kidney disease (CKD). Recent evidence suggests that acidosis, as often
      seen in patients with worsening CKD and which may enhance CKD progression, limits the
      effectiveness of statins and enhances their potential toxicity. The investigators thus
      hypothesize that correction of acidosis along with statin treatment will be a safe and
      effective therapeutic regimen to slow CKD progression in the adult ADPKD population and
      improve overall quality of life in these patients. To test this hypothesis, the investigators
      will conduct a pilot open-label randomized clinical trial in ADPKD patients with estimated
      GFR >45 min (Stage 1-3a CKD) comparing three treatment groups: control, pravastatin (40 mg po
      qd), and pravastatin plus sodium citrate solution (30 mL po total daily dose) over one year.
      During the study period, through study visits along with serial blood draws and urinary
      measurements, the investigators will evaluate safety and tolerability of these treatment
      regimens, follow renal function and investigate the role of these treatments on acidosis,
      inflammatory and metabolic biomarkers in patients enrolled at an outpatient facility. This
      study will establish the framework for larger clinical trials in ADPKD. Moreover, if the
      results of this study suggest safety/tolerability or potential benefits of statins and alkali
      therapy in this ADPKD population, the investigators will seek extramural funding for a larger
      clinical trial to test this therapeutic strategy in ADPKD.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Changes in kidney function in patients enrolled in different arms of the study

Secondary Outcome

 Urinary alkalinization changes

Condition

Autosomal Dominant Polycystic Kidney Disease

Intervention

Pravastatin

Study Arms / Comparison Groups

 ARM I: Control group
Description:  Standard therapy alone

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

January 30, 2019

Completion Date

December 31, 2020

Primary Completion Date

December 31, 2020

Eligibility Criteria

        Inclusion Criteria:

          1. Patient voluntarily gives informed consent to participate in the study and signed
             study's IC and HIPAA.

          2. Patient is age 18 or older at the time of consent.

          3. If applicable, female of reproductive potential (Females who are successfully
             sterilized (surgical sterilization methods include hysterectomy, bilateral tubal
             ligation, or bilateral oophorectomy) or are postmenopausal (defined as amenorrhea for
             at least 12 consecutive months) are not considered to be of reproductive potential)
             must be non-pregnant (as confirmed by a urine pregnancy test at screening) and
             non-lactating, and agree:

               1. Either abstain from intercourse (when it is in line with their preferred and
                  usual lifestyle), or

               2. Use 2 medically acceptable, highly-effective forms of contraception for the
                  duration of study, and at least 30 days after discontinuing study drug
                  (highly-effective forms of contraception can include approved hormonal
                  contraceptives (oral, injectable, and implantable), and barrier methods (such as
                  a condom or diaphragm) when used with a spermicide.))

          4. Patients has ADPKD diagnosed by unified criteria using a combination of ultrasound
             results, genotyping and MRI as needed (1, 2). Kidney ultrasound is usually used for
             screening because it is safe, effective, and inexpensive. Diagnostic criteria are
             based upon whether the genotype is known. Disease severity varies between the
             different genotypes. The great majority of patients at risk for ADPKD are from
             families with an unknown genotype. This diagnosis will take place prior to recruitment
             / inclusion into the study.

             The following ultrasonographic criteria for the diagnosis of ADPKD are for at-risk
             patients from families of where the genotype is not known:

               1. If the patient is between 18 and 39 years of age, at least three unilateral or
                  bilateral kidney cysts. The specificity and positive predictive value at this
                  age-range is 100 percent. (sensitivity of 82 and 96 percent for individuals
                  between 15 and 29 years and between 30 to 39 years of age, respectively).

               2. If the patient is 40 to 59 years of age, at least two cysts in each kidney
                  (sensitivity, specificity, and positive predictive value of 90, 100, and 100
                  percent, respectively).

               3. Among individuals 60 years or older, at least four cysts in each kidney. (100
                  percent sensitivity and specificity).

          5. The above patients with estimated GFR ≥30 ml/min i.e. with stage 1-3b CKD

          6. Plasma bicarbonate ≤ 25 mMol/L

          7. Metabolic acidosis

          8. The patient agrees to immediately inform Investigator and research coordinator of any
             changes or planned changes in concomitant medication

        Exclusion Criteria

          1. Patients with known allergy or sensitive to Pravastatin or NaCitrate

          2. Acute coronary disease, liver disease, muscle disease, or a history of pulmonary edema

          3. Creatine Phospho Kinase (CPK) > 2ULN (2.5 ULN in African Americans). Elevated creatine
             phosphokinase could be a marker of rhabdomyolysis, which is a potential side effect of
             pravastatin. In general, patients with African American ancestry can have higher
             normal level of CPK

          4. Patients with systemic disease that impacting kidney per Investigator's decision

          5. Patients with known unstable cerebral aneurysm per Investigator's decision

          6. Pregnancy or lactation, or patients who refuse to use recommended contraception
             methods

          7. Proteinuria > 500 mg/day

          8. History of non-compliance of medication per Investigator's decision

          9. Patients with uncontrolled hypertension, edema, or development of severe MA as per
             Investigator's decision

         10. History of cancer

         11. History of liver disease: hepatic failure/shock, cirrhosis

         12. Current or planned use of any of prohibited concomitant medication

         13. Patients with history of nephrolithiasis

        Following medications prohibited at the time of enrollment and during the study and if the
        patient is started on these medications then the patient will be excluded from the study:

          -  rapamycin or its analogues

          -  tolvaptan

          -  spironolactone

          -  cimetidine and ketoconazole

          -  erythromycin

          -  cyclosporine

          -  gemfibrozil

          -  colchicine

          -  niacin (>1 g/day)

          -  other lipid lowering medications in the class of statins
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 323442-1040, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04284657

Organization ID

HS-18-00170


Responsible Party

Principal Investigator

Study Sponsor

University of Southern California


Study Sponsor

, , 


Verification Date

February 2020