Back to resultsPravastatin as a Prophylactic to Reduce Endothelial Injury in Pediatric Patients With Elevated Body Mass Index
Primary Purpose
Hematopoietic Stem Cell Transplant (HSCT), Endothelial Injury
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pravastatin
Sponsored by
About this trial
This is an interventional prevention trial for Hematopoietic Stem Cell Transplant (HSCT)
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
Sites / Locations
- Cincinnati Children's Hospital Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pravastatin Prophylactic Treatment
Arm Description
Outcomes
Primary Outcome Measures
Percentage of participants who developed clinically significant transaminitis, renal dysfunction and rhabdomyolysis
Every enrolled patient will have routine liver function test (LFT) and renal function profile monitoring as part of their standardized transplant care. Transaminitis is expected and often multifactorial in the HSCT population, (i.e. preparative regimen, azole antifungal prophylaxis, or post-transplant complications such as infection and GVHD), therefore, we have determined modified parameters to hold or modify the dose of pravastatin. We will modify and/or hold pravastatin dosing at the time of transaminase elevations > 3X upper limit of normal unless a clear-cut alternative explanation can be provided. Additionally, we will also check creatinine kinase (CK) levels on admission and once weekly while the patient is actively taking pravastatin to monitor for rhabdomyolysis.
Percentage of participants who adhered to the medication plan
Participants will be considered adhered to the medication plan if they took the study drug at least 70% of the time. Nursing documentation of pravastatin administration and drug diaries will be used as documentation of compliance.
Secondary Outcome Measures
Number of participants with overall survival
Number of participants with graft failure
Graft failure is defined as follows:
Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first month after transplant, without evidence of disease relapse.
Secondary graft failure refers to the loss of a previously functioning graft, resulting in cytopenia involving at least two blood cell lineages.
Number of participants with primary disease relapse
Primary disease relapse is defined as: The return of a disease or the signs and symptoms of a disease after a period of improvement.
Median number of days until neutrophil engraftment
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 10^9/L) or greater.
Median number of days until platelet engraftment
Platelet engraftment is usually defined as independence from platelet transfusion for at least 7 days with a platelet count of more than >20 × 10^9/L
Assessment of SLCO1B1 genotyping
The SLCO1B1 gene encodes for making the protein organic anion transporting polypeptide 1B1 (OATP1B1), which is the transporter for drugs, including statins, into the liver. Patients enrolled on study will have their SLCO1B1 genotyping performed from whole blood samples at baseline to determine how this affects their overall statin clearance.
Measurement of sphingosine-1-phosphate (S1P) levels in plasma
S1P levels will be measured on weekly intervals using mass spectrometry
Number of participants who adhered to the medication plan
The lipid profile is a blood test that includes measurements of cholesterol, triglycerides, High-density lipoprotein (HDL) and Low-density lipoprotein (LDL). It is a routine test that monitors cholesterol levels. Pravastatin reduces cholesterol production. The lipid profile will be measured prior to the first dose of pravastatin. After the last dose of pravastatin the lipid profile will be measured. Any reduction in total cholesterol and LDL levels will be used as a surrogate marker for medication adherence.
Full Information
NCT ID
NCT05524246
First Posted
August 24, 2022
Last Updated
February 17, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
1. Study Identification
Unique Protocol Identification Number
NCT05524246
Brief Title
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
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 27, 2023 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic Stem Cell Transplant (HSCT), Endothelial Injury
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pravastatin Prophylactic Treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pravastatin
Intervention Description
Participants will receive pravastatin orally once daily through the first 35 days after bone marrow transplant.
Primary Outcome Measure Information:
Title
Percentage of participants who developed clinically significant transaminitis, renal dysfunction and rhabdomyolysis
Description
Every enrolled patient will have routine liver function test (LFT) and renal function profile monitoring as part of their standardized transplant care. Transaminitis is expected and often multifactorial in the HSCT population, (i.e. preparative regimen, azole antifungal prophylaxis, or post-transplant complications such as infection and GVHD), therefore, we have determined modified parameters to hold or modify the dose of pravastatin. We will modify and/or hold pravastatin dosing at the time of transaminase elevations > 3X upper limit of normal unless a clear-cut alternative explanation can be provided. Additionally, we will also check creatinine kinase (CK) levels on admission and once weekly while the patient is actively taking pravastatin to monitor for rhabdomyolysis.
Time Frame
Until day 35 after bone marrow transplant when pravastatin is discontinued
Title
Percentage of participants who adhered to the medication plan
Description
Participants will be considered adhered to the medication plan if they took the study drug at least 70% of the time. Nursing documentation of pravastatin administration and drug diaries will be used as documentation of compliance.
Time Frame
Until day 35 after bone marrow transplant when pravastatin is discontinued
Secondary Outcome Measure Information:
Title
Number of participants with overall survival
Time Frame
100 days after bone marrow transplant
Title
Number of participants with graft failure
Description
Graft failure is defined as follows:
Primary graft failure is defined as no evidence of engraftment or hematological recovery of donor cells, within the first month after transplant, without evidence of disease relapse.
Secondary graft failure refers to the loss of a previously functioning graft, resulting in cytopenia involving at least two blood cell lineages.
Time Frame
100 days after bone marrow transplant
Title
Number of participants with primary disease relapse
Description
Primary disease relapse is defined as: The return of a disease or the signs and symptoms of a disease after a period of improvement.
Time Frame
100 days after bone marrow transplant
Title
Median number of days until neutrophil engraftment
Description
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 10^9/L) or greater.
Time Frame
Through study completion, an average of up to 100 days
Title
Median number of days until platelet engraftment
Description
Platelet engraftment is usually defined as independence from platelet transfusion for at least 7 days with a platelet count of more than >20 × 10^9/L
Time Frame
Through study completion, an average of up to 100 days
Title
Assessment of SLCO1B1 genotyping
Description
The SLCO1B1 gene encodes for making the protein organic anion transporting polypeptide 1B1 (OATP1B1), which is the transporter for drugs, including statins, into the liver. Patients enrolled on study will have their SLCO1B1 genotyping performed from whole blood samples at baseline to determine how this affects their overall statin clearance.
Time Frame
Baseline
Title
Measurement of sphingosine-1-phosphate (S1P) levels in plasma
Description
S1P levels will be measured on weekly intervals using mass spectrometry
Time Frame
Weekly from admission until day 35 from bone marrow transplant
Title
Number of participants who adhered to the medication plan
Description
The lipid profile is a blood test that includes measurements of cholesterol, triglycerides, High-density lipoprotein (HDL) and Low-density lipoprotein (LDL). It is a routine test that monitors cholesterol levels. Pravastatin reduces cholesterol production. The lipid profile will be measured prior to the first dose of pravastatin. After the last dose of pravastatin the lipid profile will be measured. Any reduction in total cholesterol and LDL levels will be used as a surrogate marker for medication adherence.
Time Frame
Through study completion, an average of 35 days after bone marrow transplant
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ormarie Vazquez Silva
Phone
513-803-0183
Email
Ormarie.VazquezSilva@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane Koo, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ormarie Vazquez Silva
Phone
513-803-0183
Email
Ormarie.VazquezSilva@cchmc.org
First Name & Middle Initial & Last Name & Degree
Jane Koo, MD
12. IPD Sharing Statement
Learn more about this trial
Pravastatin as a Prophylactic to Reduce Endothelial Injury in Pediatric Patients With Elevated Body Mass Index
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