Pravastatin + Alkali Therapy for Polycystic Kidney Disease

(ADPKD-SAT Trial)

Overseen By Nuria M Pastor-Soler, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: Rapamycin, Tolvaptan, Spironolactone, others

Disqualifiers: Coronary disease, Liver disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications, including rapamycin, tolvaptan, spironolactone, cimetidine, ketoconazole, erythromycin, cyclosporine, gemfibrozil, colchicine, niacin (more than 1 g/day), and other statins. If you are on any of these, you will need to discontinue them to participate.

How is the drug Pravastatin + Alkali Therapy unique for treating Polycystic Kidney Disease?

Pravastatin + Alkali Therapy is unique because it combines a cholesterol-lowering drug (Pravastatin) with an alkali agent (Sodium Citrate) to potentially address both cardiovascular and metabolic aspects of Polycystic Kidney Disease, which is different from standard treatments that typically focus on managing symptoms like high blood pressure or kidney function alone. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Pravastatin for Polycystic Kidney Disease?

Pravastatin is known to lower cholesterol levels effectively, reducing total cholesterol by 15-30% and LDL cholesterol by 15-40% in patients with hypercholesterolemia. While this data is specific to cholesterol management, it suggests Pravastatin's potential in managing conditions related to cholesterol and lipid levels. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD) and moderate kidney function (stage 1-3b CKD), not pregnant or breastfeeding, willing to use effective contraception. Excludes those with significant protein in urine, cancer history, liver disease, certain allergies, uncontrolled blood pressure, edema or severe metabolic acidosis.

Inclusion Criteria

You have a condition called metabolic acidosis.

Your blood has a low level of bicarbonate.

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

Exclusion Criteria

You have more than 500 milligrams of protein in your urine every day.

You have had cancer in the past.

You have had serious liver problems like liver failure, cirrhosis, or liver shock.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive Pravastatin and/or Sodium Citrate treatment over one year to evaluate safety, tolerability, and effects on kidney function and other biomarkers

52 weeks

Regular visits for blood draws and urinary measurements

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pravastatin
• Sodium Citrate

Trial Overview The study is testing the effectiveness of Pravastatin and sodium citrate over one year in patients with ADPKD. It's an open-label trial where all participants know which treatments they are receiving.

How Is the Trial Designed?

Group I: ARM I: Control group Active Control 1 Intervention

Standard therapy alone

Group II: ARM II: PRAVASTATIN Active Control 1 Intervention

Standard therapy and PRAVASTATIN 40 mg QD

Group III: ARM III: PRAV + Sodium Citrate Active Control 2 Interventions

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

Pravastatin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Pravachol for:

• High Cholesterol
• Hyperlipoproteinemia
• Myocardial Infarction - Prophylaxis
• Revascularization Procedures - Prophylaxis

Approved in European Union as Pravastatin for:

• Hypercholesterolaemia
• Mixed dyslipidaemia
• Prevention of cardiovascular events

Approved in Canada as Pravastatin for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular events

Approved in Japan as Pravastatin for:

• Hypercholesterolemia
• Familial hypercholesterolemia

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

Pravastatin is an effective HMG-CoA reductase inhibitor that significantly lowers total cholesterol by 15-30% and LDL cholesterol by 15-40% in patients with hypercholesterolemia, including those with diabetes, when taken in doses of 10-40 mg/day.

It is generally well tolerated with fewer reported adverse effects compared to similar medications like lovastatin, suggesting it may be a safer option for lipid-lowering therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pravastatin: a new drug for the treatment of hypercholesterolemia. Jungnickel, PW., Cantral, KA., Maloley, PA.[2013]

The study developed enteric surface-coated nanocubosomal dispersions of pravastatin sodium (PVS) that significantly improved its oral bioavailability in rats compared to traditional aqueous solutions, indicating a more effective delivery method.

The optimized E-F8 system demonstrated controlled-release characteristics, with a delayed peak absorption time and prolonged drug presence in the body, enhancing the potential for better therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions. Tayel, SA., El-Nabarawi, MA., Tadros, MI., et al.[2017]

Sodium polystyrene sulfonate (SPS) is the standard treatment for hyperkalemia, but newer agents like sodium zirconium cyclosilicate and patiromer may provide better options.

The introduction of these new agents could improve patient outcomes in managing hyperkalemia, suggesting a need for further evaluation of their safety and efficacy compared to SPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium-Binding Agents for the Clinical Management of Hyperkalemia. Chaitman, M., Dixit, D., Bridgeman, MB.[2022]

In a study of 114 patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), a single 30g dose of sodium polystyrene sulfonate (SPS) significantly reduced serum potassium levels by a median of 0.8 mEq/L within 24 hours, indicating its efficacy in treating hyperkalemia.

While SPS was effective in lowering potassium, gastrointestinal side effects were reported in 5% of patients, raising concerns about potential risks associated with its use in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease. Hunt, TV., DeMott, JM., Ackerbauer, KA., et al.[2023]

Patiromer is an effective treatment for hyperkalaemia, significantly reducing serum potassium levels in patients with chronic kidney disease and allowing them to continue using RAAS inhibitors for up to 52 weeks.

The medication is generally well tolerated, with a low risk of causing low potassium levels (hypokalaemia), although mild to moderate gastrointestinal disorders and low magnesium levels (hypomagnesaemia) were the most common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patiromer: A Review in Hyperkalaemia. Blair, HA.[2022]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Pravastatin: a new drug for the treatment of hypercholesterolemia. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Duodenum-triggered delivery of pravastatin sodium: II. Design, appraisal and pharmacokinetic assessments of enteric surface-decorated nanocubosomal dispersions. [2017]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Formulation and Evaluation of Pravastatin Sodium-Loaded PLGA Nanoparticles: In vitro-in vivo Studies Assessment. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of pravastatin in patients on chronic hemodialysis. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of pravastatin on plasma lipoprotein and apolipoprotein levels in primary hypercholesterolemia. The Southeastern Michigan Collaborative Group. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Potassium-Binding Agents for the Clinical Management of Hyperkalemia. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Additional mechanisms of nafamostat mesilate-associated hyperkalaemia. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Patiromer in Hyperkalemic Patients with CKD: A Pooled Analysis of Three Randomized Trials. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Patiromer: A Review in Hyperkalaemia. [2022]