Fontan Circulation
Conditions
Keywords
Fontan, FALD
Brief summary
This is a single center, open-label, prospective, investigation to quantify the effects liver congestion and fibrosis has on hepatic drug metabolism and transport in children, adolescents, and young adults with Fontan circulation.
Interventions
DRUGSildenafil 10mg oral tablet (participants <20kg), or 20mg oral tablet (participants ≥20kg)
A single oral dose of sildenafil will be administered to all study subjects.
DRUGPravastatin 20 mg oral tablet (ages <13 years), or 40 mg oral tablet (≥14 years)
A single oral dose of pravastatin will be administered to all study subjects.
Sponsors
Indiana Clinical and Translational Sciences Institute
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Children's Mercy Hospital Kansas City
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a single center, open-label, prospective, investigation to quantify the effects of liver congestion and fibrosis has on hepatic statin transport (SA1) and response (SA2) in children, adolescents, and young adults with Fontan circulation.
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \> 8 years * Status Post Fontan Completion * Ability to provide informed permission-assent (\<18 years) or consent (≥18 years) * Fasting overnight (\ 8 hours)
Exclusion criteria
* Pregnancy * Non-fasting * Non-removable metal in body or where magnetic resonance imaging (MRI) is considered unsafe * Sildenafil and/or Pravastatin therapy within last 2 months * History of underlying or laboratory evidence of underlying intestinal, metabolic, autoimmune, renal disease that can alter Sildenafil and Pravastatin disposition (absorption, metabolism, distribution, or clearance) * Pharmacotherapy that interacts with Sildenafil (cytochrome P450 3A4 and P450 3A5 (CYP3A4/5) inducers/inhibitors) and/or Pravastatin (organic anion transporting polypeptide (OATP1B1) inducers/inhibitors) * Inability to swallow a tablet * \>5X the age-specific upper limit of normal for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total and conjugated bilirubin * Diarrhea in the last 24 hours \*History of solid organ transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sildenafil concentration as measured by area under the curve (AUC) | 2 years | Area under the time-exposure curve (AUC 0-n) for sildenafil as determinants of the dose-exposure relationship. |
| Pravastatin concentration as measured by area under the curve (AUC) | 2 years | Area under the time-exposure curve (AUC 0-n) for pravastatin as determinants of the dose-exposure relationship. |
Countries
United States
Contacts
Primary ContactJonthan Wagner, DO
Outcome results
None listed