Clinical trial NCT05524246: Pravastatin as a Prophylactic to Reduce Endothelial Injury in Pediatric Patients With Elevated Body Mass Index
Official title: Pilot Trial of Pravastatin as a Novel Prophylactic Medicine to Reduce Endothelial Injury in Pediatric Patients With Elevated Body Mass Index
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematopoietic Stem Cell Transplant (HSCT)
Endothelial Injury
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2022-09-01
Enrollment: 25
Sex: ALL
Minimum age (years): 2
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Chemotherapy and radiation used in patients undergoing bone marrow transplant (BMT) disrupts the endothelial lining (a thin layer of cells inside the blood vessels) which is found all throughout the body including the kidney, heart, lungs, and intestines. Disruption of this endothelial lining can lead to complications such as graft-vs-host disease (GVHD), thrombotic microangiopathy (TMA) and veno-occlusive disease (VOD). 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 endothelial injury after BMT.

The investigator hypothesizes that prophylactic pravastatin in pediatric allogeneic hematopoietic stem cell transplant recipients with elevated BMI is safe and feasible.


Eligibility criteria: Inclusion Criteria:

* Scheduled for allogeneic stem cell transplant
* Ages ≥ 2 - ≤ 25 years old
* Elevated BMI defined by the Center for Disease Control and Prevention definitions. Both overweight (BMI between 85th-94th percentile) and obese (BMI \>95th percentile) patients are eligible
* All diagnoses are eligible

Exclusion Criteria:

* Patients with documented anaphylaxis to pravastatin
* Patients will be ineligible if they are unable to take medication orally or enterally (i.e. intestinal failure)
* Patients with elevations in ALT/AST levels 3x ULN at time of enrollment
* Patients with renal impairment as clinically measured (GFR \<50 ml/min/1.73m2) at time of enrollment
* Patients with known neuromuscular and metabolic disorders associated with an increased risk of rhabdomyolysis (ie metabolic muscle disorders, mitochondrial disorders, and muscular dystrophies)
* Patients taking any drugs that are known substrates for OATP1B1 and OATP1B3 transporters

Primary outcomes:
measure: Percentage of participants who developed clinically significant transaminitis, renal dysfunction and rhabdomyolysis
timeFrame: Until day 35 after bone marrow transplant when pravastatin is discontinued
measure: Percentage of participants who adhered to the medication plan
timeFrame: Until day 35 after bone marrow transplant when pravastatin is discontinued
Secondary outcomes:
measure: Number of participants with overall survival
timeFrame: 100 days after bone marrow transplant
measure: Number of participants with graft failure
timeFrame: 100 days after bone marrow transplant
measure: Number of participants with primary disease relapse
timeFrame: 100 days after bone marrow transplant
measure: Median number of days until neutrophil engraftment
timeFrame: Through study completion, an average of up to 100 days
measure: Median number of days until platelet engraftment
timeFrame: Through study completion, an average of up to 100 days
measure: Assessment of SLCO1B1 genotyping
timeFrame: Baseline
measure: Measurement of sphingosine-1-phosphate (S1P) levels in plasma
timeFrame: Weekly from admission until day 35 from bone marrow transplant
measure: Number of participants who adhered to the medication plan
timeFrame: Through study completion, an average of 35 days after bone marrow transplant
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Jane Koo, MD
role: PRINCIPAL_INVESTIGATOR
References: