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 trial aims to evaluate the effectiveness of combining Pravastatin (a cholesterol-lowering drug) and Sodium Citrate (an alkali therapy) in treating autosomal dominant polycystic kidney disease (ADPKD), a condition where cysts form in the kidneys and may lead to kidney failure. Participants will be divided into three groups: one receiving standard treatment, another adding Pravastatin, and the third adding both Pravastatin and Sodium Citrate to their standard care. The trial seeks individuals with ADPKD who experience frequent kidney cysts and maintain normal kidney function (not too severe kidney disease). As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that pravastatin, a medication commonly used to lower cholesterol, is generally well-tolerated. The FDA has already approved it for other uses, such as reducing the risk of heart problems. Most people tolerate it well, though some might experience muscle pain or digestive issues.

Regarding the combination of pravastatin and sodium citrate, information remains uncertain. While some research exists on similar treatments, no studies have definitively shown this combination to be safe and effective for treating polycystic kidney disease, a condition where cysts form in the kidneys. This trial is in an early stage, so the safety of the treatment is still under study. Testing in humans suggests some initial confidence in its safety. Always consult a doctor about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for polycystic kidney disease, which often include blood pressure medications and pain relievers, the new approach combines pravastatin and sodium citrate to target the disease differently. Pravastatin, typically used to lower cholesterol, is being explored for its potential to slow kidney cyst growth. Sodium citrate, on the other hand, may help manage the acidity levels in the body, which can be beneficial for kidney health. Researchers are excited because this combination might provide a dual-action approach, addressing both cyst growth and kidney function in ways current treatments do not.

What evidence suggests that this trial's treatments could be effective for polycystic kidney disease?

This trial will compare different treatment approaches for Autosomal Dominant Polycystic Kidney Disease (ADPKD). Research has shown that pravastatin, a cholesterol-lowering drug, does not significantly benefit kidney health in adults with ADPKD. Studies found that pravastatin neither slowed kidney growth nor improved kidney function. In this trial, one group will receive standard therapy with pravastatin, while another group will receive pravastatin combined with sodium citrate. However, combining pravastatin with sodium citrate did not show clear benefits for adults with good kidney function. Statins like pravastatin may help younger patients by reducing inflammation. Overall, evidence suggests these treatments are not very effective for adults with ADPKD. ^{3 5 6 7 8}

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41077128/

A randomized controlled trial evaluated the effect of ... Conclusions: Among adult patients with ADPKD and preserved kidney function, pravastatin did not slow the increase in HtTKV and had no effect on ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1551714423003464

Statin therapy in patients with early-stage autosomal ... However, there is no evidence that pravastatin therapy may impact kidney outcomes in adult patients with ADPKD. Indeed, a post-hoc analysis of data from the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04284657

Pravastatin and Alkali Therapy in Patients With Autosomal ... Cholesterol-lowering agents called statins have shown promise in the treatment of younger ADPKD patients, reducing inflammation and progression as assessed by ...

4. docwirenews.com docwirenews.com/post/effects-of-pravastatin-on-kidney-outcomes-in-adults-with-adpkd

Effects of Pravastatin on Kidney Outcomes in Adults With ... No significant differences were observed in HtTKV changes, kidney function, or renal blood flow between patients in the pravastatin and placebo ...

5. researchgate.net researchgate.net/publication/396418930_A_randomized_controlled_trial_evaluated_the_effect_of_pravastatin_on_kidney_disease_outcomes_in_adult_patients_with_early-stage_autosomal_dominant_polycystic_kidney_disease

A randomized controlled trial evaluated the effect of ... A randomized controlled trial evaluated the effect of pravastatin on kidney disease outcomes in adult patients with early-stage autosomal ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK551621/

Pravastatin - StatPearls - NCBI Bookshelf - NIH Patients with Renal Impairment: A starting dose of 10 mg pravastatin once daily is recommended in patients with severe renal impairment. Patients with Liver ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2016/019898s066lbl.pdf

pravachol - accessdata.fda.gov In hypercholesterolemic patients without clinically evident coronary heart disease (CHD),. PRAVACHOL (pravastatin sodium) is indicated to: • reduce the risk ...

8. go.drugbank.com go.drugbank.com/drugs/DB00175

Pravastatin: Uses, Interactions, Mechanism of Action Pravastatin is indicated for primary prevention of coronary events hypercholesterolemic patients without clinical evidence of coronary heart disease.