Endothelial Injury > Pravastatin

Pravastatin for Endothelial Injury in Pediatric Patients

Recruiting in Palo Alto (17 mi)

Overseen By Jane Koo, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

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

Approved in 4 jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if pravastatin, a cholesterol-lowering drug, can protect blood vessel linings in children with high BMI undergoing bone marrow transplants. The goal is to see if it can prevent serious complications by keeping these blood vessels healthy.

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).

How is the drug pravastatin unique for treating endothelial injury in pediatric patients?

Pravastatin is unique because it is a statin that has been shown to be safe and effective in lowering cholesterol levels in children with familial hypercholesterolemia, and it has a specific mechanism of action that inhibits HMG-CoA reductase, an enzyme involved in cholesterol production. Its use in pediatric patients is novel due to its ability to lower LDL cholesterol and increase HDL cholesterol, which may help in managing endothelial injury.

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Eligibility Criteria

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.

I am currently taking medication that affects liver transport proteins.

Patients with documented anaphylaxis to pravastatin

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cincinnati Children's Hospital Medical Center Cincinnati, OH

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati Lead Sponsor

References

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

Impact of Genetic Variation on Pravastatin Systemic Exposure in Pediatric Hypercholesterolemia. [2020] This study investigated the impact of SLCO1B1 genotype on pravastatin systemic exposure in children and adolescents with hypercholesterolemia. Participants (8-20 years) with at least one allelic variant of SLCO1B1 c.521T>C (521TC, n = 15; 521CC, n = 2) and wild-type controls (521TT, n = 15) completed a single oral dose pharmacokinetic study. Interindividual variability of pravastatin acid (PVA) exposure within SLCO1B1 genotype groups exceeded the approximately twofold difference in mean PVA exposure observed between SLCO1B1 genotype groups (P > 0.05, q > 0.10). The 3'α-iso-pravastatin acid and lactone isomer formation in the acidic environment of the stomach prior to absorption also was variable and affected PVA exposure in all genotype groups. The SLCO1B1 c.521 gene variant contributing to variability in systemic exposure to PVA in our pediatric cohort was comparable to previous studies in adults. However, other demographic and physicochemical factors seem to also contribute to interindividual variability in the dose-exposure relationship.

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

Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia. [2013] Pravastatin is a widely used statin in adults, but its pharmacokinetics in children is not known. Our aim was to determine the single-dose pharmacokinetics and the lipid-lowering effect and safety of short-term administration of pravastatin in children.

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

Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. [2013] The safety, tolerability, and efficacy of a 12-wk treatment with pravastatin, 5, 10, and 20 mg/d, was evaluated in 72 children with heterozygous familial hypercholesterolemia (FH) in a double-blind, randomized and placebo-controlled study. The results show that pravastatin was well tolerated and that adverse events were mild and equally distributed among the three treatment groups. Plasma total and LDL cholesterol levels were significantly reduced in all pravastatin treatment groups, in comparison with the control group; -24.6% (-28.1 to 21.0) and -32.9% (-37.0 to -28.6), for mean change and 95% confidence interval, respectively. In four children plasma LDL cholesterol levels were reduced within normal limits for sex and age. HDL cholesterol increased in the pravastatin 20-mg group, +10.8% (+3.4 to +18.8), whereas plasma apo B100 and very LDL (VLDL) cholesterol levels were reduced within all pravastatin-treated groups -26.8% (-31.2 [corrected] to -21.7) and -24.5% (-35.0 to -12.3). These data show that short-term pravastatin treatment of children with FH is safe and effective, although long-term dose titration studies with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors need to be performed, to reduce plasma LDL cholesterol levels below a predefined level. The results of these studies have to be awaited before new treatment strategies are to be considered in these children.

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

Steady-state pharmacokinetics of pravastatin in children with familial hypercholesterolaemia. [2018] To determine pharmacokinetic data for pravastatin in children, since current data are insufficient in this age group.

5. 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] Pravastatin sodium (PVS) is a freely water-soluble HMG-CoA inhibitor that suffers from instability at gastric pH, extensive first pass metabolism, short elimination half-life (1-3 h) and low oral bioavailability (18%).