A Fully Remote Feasibility Trial of Phenylbutyrate for SLC6A1-Related Disorders

Inclusion Criteria: * Confirmed diagnosis of SLC6A1-related disorder based on a pathogenic or likely pathogenic variant in the SLC6A1 gene * Age 2-60 years at time of consent * Active clinical seizures, defined as ≥4 seizures in the 4 weeks prior to enrollment * Seizures persisting despite an adequate trial of ≥2 prior antiseizure medications at therapeutic doses * Stable antiseizure medication regimen for ≥4 weeks prior to enrollment * Parent, legal guardian, or legally authorized representative (LAR) able to provide informed consent and participate in digital follow-up assessments * Local licensed physician identified for ordering laboratory testing, EEG, and clinical evaluation as needed * English-speaking caregiver for consent and study communication Exclusion Criteria: * Larger 3p25 chromosomal deletion extending beyond SLC6A1 and SLC6A11 to encompass additional genes * Early-infantile developmental and epileptic encephalopathy (DEE) phenotype * Epileptic spasms within the 6 months prior to enrollment * Hepatic impairment (AST or ALT \>2× the upper limit of normal) * Renal impairment (eGFR \<60 mL/min/1.73m²) * Thrombocytopenia (platelet count \<150 × 10³/μL) * Inborn errors of beta-oxidation * Pancreatic insufficiency or intestinal malabsorption * Known hypersensitivity to phenylbutyrate or any of its components * Participation in another interventional investigational study within 30 days or 5 half-lives of the investigational product, whichever is longer * Current use of alfentanil, quinidine, cyclosporine, or probenecid due to clinically significant interactions with phenylbutyrate based on CYP3A4 modulation * Pregnancy or breastfeeding * Any condition that in the investigator's judgment would interfere with study participation or safety monitoring This is a fully remote study. Participants may enroll from any U.S. state. No facility visit is required.