Pravastatin for Endothelial Injury in Pediatric Patients

Overseen By Ormarie Vazquez Silva

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Pravastatin

Must not be taking: OATP1B1/OATP1B3 substrates

Disqualifiers: Anaphylaxis to pravastatin, Renal impairment, Neuromuscular disorders, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether pravastatin, a medication, is safe and can reduce blood vessel damage in young patients undergoing bone marrow transplants. The treatment aims to prevent complications such as graft-vs-host disease and other serious conditions that can occur after transplant surgeries. Children and young adults scheduled for a transplant and with higher body weight might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially beneficial therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking drugs that interact with certain transporters (OATP1B1 and OATP1B3).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking drugs that interact with certain transporters (OATP1B1 and OATP1B3).

Is there any evidence suggesting that pravastatin is likely to be safe for humans?

Research has shown that pravastatin is generally safe and well-tolerated in children. In one study involving 72 children with a genetic condition causing high cholesterol, the treatment caused only mild side effects. Another set of early data suggests that using pravastatin as a preventive measure is both safe and practical for children and young adults undergoing bone marrow transplants. This offers reassurance about its safety in similar situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pravastatin is unique because it targets endothelial injury, which is damage to the cells lining blood vessels, especially in pediatric patients. This is different from standard treatments that generally focus on cholesterol management in adults. Researchers are excited about pravastatin for this condition because it may offer a new way to protect children's vascular health by preventing or reducing endothelial damage, something current options don't specifically address. Additionally, pravastatin's safety profile in adults makes it a promising candidate for exploring its benefits in younger populations.

What evidence suggests that pravastatin might be an effective treatment for endothelial injury in pediatric patients undergoing BMT?

Research has shown that pravastatin, which participants in this trial will receive as part of the Pravastatin Prophylactic Treatment arm, effectively lowers cholesterol levels. This is crucial because high cholesterol can damage blood vessels. Studies have demonstrated that pravastatin reduces total cholesterol by 18% and LDL (bad cholesterol) by 21%. Lowering cholesterol helps protect the inner lining of blood vessels from damage. While pravastatin is commonly used to treat high cholesterol, it might also help prevent issues like graft-vs-host disease by safeguarding these blood vessels. Although more research is needed on its use in bone marrow transplant patients, these findings suggest it could be beneficial. ^{1 3 6 7 8}

Who Is on the Research Team?

Jane Koo, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 2-25 with an elevated BMI who are scheduled for a stem cell transplant. It's open to all diagnoses, but not for those with kidney issues, taking certain drugs, allergic to pravastatin, unable to take oral medication, or have specific muscle disorders.

Inclusion Criteria

My condition does not limit my eligibility based on diagnosis.

My BMI classifies me as overweight or obese according to CDC guidelines.

I am between 2 and 25 years old.

Exclusion Criteria

My kidney function is reduced.

Patients with documented anaphylaxis to pravastatin

I am currently taking medication that affects liver transport proteins.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pravastatin as a prophylactic treatment to reduce endothelial injury after bone marrow transplant

5 weeks

Weekly monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 weeks

Long-term follow-up

Participants are monitored for graft failure and primary disease relapse

100 days

What Are the Treatments Tested in This Trial?

Interventions

• Pravastatin

Trial Overview The study tests if Pravastatin can prevent damage to the endothelial lining in blood vessels after bone marrow transplants in young patients with high body weight. The goal is to see if it reduces complications like GVHD and VOD.

How Is the Trial Designed?

Group I: Pravastatin Prophylactic Treatment Experimental Treatment 1 Intervention

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?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

A 12-week study involving 72 children with heterozygous familial hypercholesterolemia showed that pravastatin was well tolerated, with mild adverse events evenly distributed across treatment groups.

Pravastatin significantly reduced plasma total and LDL cholesterol levels in all treatment groups compared to placebo, indicating its efficacy in managing cholesterol levels in children with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. Knipscheer, HC., Boelen, CC., Kastelein, JJ., et al.[2013]

In a study involving 20 children aged 4.9 to 15.6 years with familial hypercholesterolemia, a single 10 mg dose of pravastatin showed a pharmacokinetic profile similar to that in adults, with a peak plasma concentration reached in about 1.4 hours.

After 8 weeks of daily treatment, pravastatin significantly reduced total cholesterol by 18% and low-density lipoprotein (LDL) cholesterol by 21%, indicating its effectiveness in lowering cholesterol levels in children, with few transient side effects and no significant liver or muscle enzyme increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia. Hedman, M., Neuvonen, PJ., Neuvonen, M., et al.[2013]

In a study of 24 children aged 8-16 with familial hypercholesterolemia, pravastatin showed a 27% reduction in low-density lipoprotein cholesterol after 14 days, indicating its efficacy in lowering cholesterol levels in this age group.

Pharmacokinetic analysis revealed that prepubertal children had a higher maximum plasma concentration (C(max)) of pravastatin compared to adolescents, suggesting that dosing may need to be adjusted for younger children, potentially starting at half the adult dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steady-state pharmacokinetics of pravastatin in children with familial hypercholesterolaemia. Wiersma, HE., Wiegman, A., Koopmans, RP., et al.[2018]

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]

The study found that the SLCO1B1 genotype significantly influences the systemic exposure to pravastatin in children and adolescents with hypercholesterolemia, with specific variants (521TC and 521CC) showing different levels of drug exposure compared to wild-type controls (521TT).

Despite the genetic influence, there was considerable variability in pravastatin exposure among individuals within the same genotype group, suggesting that other demographic and physicochemical factors also play a role in how the drug is processed in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia. Wagner, JB., Abdel-Rahman, S., Gaedigk, R., et al.[2020]

Citations

1. withpower.com withpower.com/trial/phase-1-wounds-and-injuries-8-2022-16a1d

Pravastatin for Endothelial Injury in Pediatric Patients After 8 weeks of daily treatment, pravastatin significantly reduced total cholesterol by 18% and low-density lipoprotein (LDL) cholesterol by 21%, indicating ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4559520/

Pravastatin Therapy and Biomarker Changes in Children ... The positive outcome of the study (10) supports early therapeutic intervention and pravastatin as an effective agent to slow the progression of ADPKD. However, ...

3. publications.aap.org publications.aap.org/pediatriccare/drug-monograph/18/5770/Pravastatin

Pravastatin | Drug Lookup | Pediatric Care Online Dosing: Pravastatin 40 to 80 mg/day is considered a moderate-intensity statin (generally reduces low-density lipoprotein cholesterol [LDL-C] by ~30% to 49%). If ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5103646/

Pediatric Statin Administration: Navigating a Frontier with ... This review describes the updated guidelines for screening and management of pediatric dyslipidemia and statin disposition pathway to assist the provider in ...

5. ahajournals.org ahajournals.org/doi/10.1161/CIR.0000000000000618

Cardiovascular Risk Reduction in High-Risk Pediatric ... This scientific statement presents considerations for clinical management regarding the assessment and risk reduction of select pediatric populations at high ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05524246?tab=table

Pravastatin as a Prophylactic to Reduce Endothelial Injury ... The purpose of this research study is to help investigators see if pravastatin is safe and well tolerated in patients undergoing BMT to see if it will reduce ...

7. astctjournal.org astctjournal.org/article/S2666-6367(25)00263-5/fulltext

Pravastatin Prophylaxis Is Safe and Feasible in Children ... Preliminary data suggest that pravastatin prophylaxis is both safe and feasible in pediatric and young adult HSCT recipients with elevated BMI.

8. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT05524246/

Trial | NCT05524246 The purpose of this research study is to help investigators see if pravastatin is safe and well tolerated in patients undergoing BMT to see if it will reduce ...