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.