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

NCT04284657 | Completed Phase 2 FDA Drug

• 1 other identifier: HS-18-00170
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Autosomal Dominant Polycystic Kidney Disease

Keywords

Polycystic Kidney Disease; ADPKD; PKD

Outcome Measures

Primary Outcomes (5)

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

  The investigators will estimate the effect of Pravastatin and NaCitrate on kidney function in patients with ADPKD compared to Pravastatin alone or Standard therapy: serum creatinine and serum blood urea nitrogen, serum electrolytes contribute to evaluate kidney function.

  12 months

• Changes in liver function in patients enrolled in different arms of the study

  The investigators will test liver function test panels in patients with ADPKD compared to Pravastatin alone or Standard therapy. The liver function panel should be within normal limits for enrollment and continuation in the study. Liver function tests include AST \> 3ULN, ALT \> 3ULN, Total Bilirubin \> 2 ULN, or increase in prothrombin time to abnormal level INR \>1.5 repeated two weeks apart

  12 months

• Changes in blood pressure in patients enrolled in different arms of the study

  The investigators will estimate the effect of Pravastatin and NaCitrate on blood pressure (systolic and diastolic) in patients with ADPKD compared to Pravastatin alone or Standard therapy

  12 months

• Changes in muscle injury marker function in patients enrolled in different arms of the study

  The investigators will estimate the effect of Pravastatin and NaCitrate on creatine phospho kinase (CPK) in patients with ADPKD compared to Pravastatin alone or Standard therapy.

  12 months

• Changes in muscle tenderness in patients enrolled in the study

  The investigators will estimate the effect of Pravastatin and NaCitrate on muscle tenderness in patients with ADPKD compared to Pravastatin alone or Standard therapy. The physical exam will evaluate tenderness to palpation in major muscle groups such as leg, arm and back muscles. It will be graded as presence or absence. The patients will only be enrolled if there is absence of tenderness in muscles upon palpation on physical exam. If there is tenderness on exam or the patient reports tenderness that is then confirmed by exam the patient will be removed from the study.

  12 months

Secondary Outcomes (3)

• Urinary alkalinization changes

  12 months

• Inflammatory markers in blood and urine

  12 months

• AMPK pathway activation

  12 months

Study Arms (3)

ARM I: Control group

NO INTERVENTION

Standard therapy alone

ARM II: PRAVASTATIN

ACTIVE COMPARATOR

Standard therapy and PRAVASTATIN 40 mg QD

Drug: Pravastatin

ARM III: PRAV + Sodium Citrate

ACTIVE COMPARATOR

Standard therapy and PRAVASTATIN 40 mg QD and Sodium Citrate (up to 30 mL TID)

Drug: Pravastatin; Drug: sodium citrate

Interventions

Pravastatin DRUG

Pravastatin 40 mg QD

ARM II: PRAVASTATIN; ARM III: PRAV + Sodium Citrate

sodium citrate DRUG

sodium citrate up to 30 ml TID

ARM III: PRAV + Sodium Citrate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient voluntarily gives informed consent to participate in the study and signed study's IC and HIPAA.
• Patient is age 18 or older at the time of consent.
• 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:
• Either abstain from intercourse (when it is in line with their preferred and usual lifestyle), or
• 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.))
• The following ultrasonographic criteria for the diagnosis of ADPKD are for at-risk patients from families of where the genotype is not known:
• 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).
• 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).
• Among individuals 60 years or older, at least four cysts in each kidney. (100 percent sensitivity and specificity).
• The above patients with estimated GFR ≥30 ml/min i.e. with stage 1-3b CKD
• Plasma bicarbonate ≤ 25 mMol/L
• Metabolic acidosis
• The patient agrees to immediately inform Investigator and research coordinator of any changes or planned changes in concomitant medication

You may not qualify if:

• Patients with known allergy or sensitive to Pravastatin or NaCitrate
• Acute coronary disease, liver disease, muscle disease, or a history of pulmonary edema
• 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
• Patients with systemic disease that impacting kidney per Investigator's decision
• Patients with known unstable cerebral aneurysm per Investigator's decision
• Pregnancy or lactation, or patients who refuse to use recommended contraception methods
• Proteinuria \> 500 mg/day
• History of non-compliance of medication per Investigator's decision
• Patients with uncontrolled hypertension, edema, or development of severe MA as per Investigator's decision
• History of cancer
• History of liver disease: hepatic failure/shock, cirrhosis
• Current or planned use of any of prohibited concomitant medication
• 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

Sponsors & Collaborators

• University of Southern California: lead

Study Sites (1)

Keck School of Medicine of University of Southern California

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Polycystic Kidney Diseases

Interventions

Pravastatin; Sodium Citrate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Citric Acid; Citrates; Tricarboxylic Acids; Acids, Acyclic; Carboxylic Acids

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: February 26, 2020
• Study Start: January 30, 2019
• Primary Completion: August 4, 2025
• Study Completion: August 4, 2025
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)