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

• Status: Recruiting
• Trial end date: 2020-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Southern California
• Treatments: Citric Acid; Pravastatin; Sodium Citrate

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