Recruiting
Phase 2

Phenylbutyrate

Sponsor:

Scripps Translational Science Institute

Code:

NCT07847918

Conditions

SLC6A1

Eligibility Criteria

Sex: All

Age: 2 - 60

Healthy Volunteers: Not accepted

Interventions

Glycerol Phenylbutyrate

Study Details

Brief summary:

The purpose of this study is to evaluate the feasibility of a site-less (fully remote) clinical trial using phenylbutyrate for SLC6A1-related disorders. Study participants will receive treatment with phenylbutyrate, undergo electroencephalogram (EEG) monitoring, and complete laboratory testing. Caregivers will report seizure frequency, answer questionnaires, and report side effects.

Participants will be randomly assigned to one of two groups. Randomization is stratified by age band (<7 years vs. ≥7 years) and baseline seizure frequency (≤5 vs. >5 daily seizures). One group will begin treatment immediately; the other group will have a 6-week observation period before starting treatment. All participants will receive phenylbutyrate. Treatment lasts up to 18 weeks with the option to extend for up to 3 years. Follow-up occurs at 18 weeks. If extending treatment, additional follow-up occurs at 6 months, 1 year, and then annually.

Participation is completely voluntary. There is the risk of adverse events from the study drug, phenylbutyrate, including hospitalization from metabolic acidosis. There is the risk of loss of confidentiality of your medical and personal information collected for this study. This study does not replace emergency medical care.

This is a fully remote study. Participants may enroll from any U.S. state. No facility visit is required.

Conditions

SLC6A1

Study ID

NCT07847918

Start date

Oct, 2026

Status verified date

Sep, 2026

Completion date

Oct, 2032

Anticipated

Primary completion date

Mar, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 2 - 60

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (Immediate Start)

Arm A will receive immediate treatment with phenylbutyrate beginning week 0 through week 18.

active comparator: Arm B (Delayed Start)

Arm B will have a delayed start with an observation period weeks 0-6 followed by treatment beginning at week 6 through week 18.

Interventions

Glycerol Phenylbutyrate

Glycerol phenylbutyrate oral liquid (1.1 g/mL) administered orally three times daily with food or formula, or via gastrostomy or nasogastric tube when clinically indicated. The dose is titrated over 8 weeks from a starting dose of 3.6 mL/m²/day to a target maximum of 11.2 mL/m²/day (12.4 g/m²/day), not to exceed 17.5 mL/day total, based on body surface area. Dose adjustments are made based on tolerability and safety laboratory results. Drug is obtained through self-pay via Cost Plus pharmacy with direct home delivery, or through the participant's health insurance at a designated pharmacy.

Other Name(s): Ravicti; glycerol phenylbutyrate oral liquid; GPB; 4-phenylbutyrate; 4-PBA

Primary outcome measure

  • Recruitment efficiency [ Time Frame: From study opening through end of enrollment (approximately 2 years) ]
  • Protocol adherence: seizure diary completion [ Time Frame: Weeks 0-18 ]
  • Protocol adherence: Electroencephalogram (EEG) completion [ Time Frame: Baseline, week 6 and week 18 ]
  • Protocol adherence: side effect questionnaire completion [ Time Frame: From treatment initiation through week 18 ]
  • Protocol adherence: safety laboratory completion [ Time Frame: 6 weeks after treatment initiation ]
  • Retention [ Time Frame: Week 18 ]
  • Caregiver satisfaction: overall satisfaction [ Time Frame: Week 18 ]
  • Caregiver satisfaction: acceptability [ Time Frame: Week 18 ]
  • Caregiver satisfaction: fit with daily routine [ Time Frame: Week 18 ]
  • Caregiver satisfaction: clarity of study procedures [ Time Frame: Week 18 ]
  • Caregiver satisfaction: time burden [ Time Frame: Week 18 ]
  • Caregiver satisfaction: study team communication [ Time Frame: Week 18 ]
  • Caregiver satisfaction: adequacy of remote safety monitoring [ Time Frame: Week 18 ]
  • Caregiver satisfaction: access to medical support [ Time Frame: Week 18 ]
  • Caregiver satisfaction: Research Electronic Data Capture (REDCap) usability [ Time Frame: Week 18 ]
  • Caregiver satisfaction: instructional video usefulness [ Time Frame: Week 18 ]
  • Caregiver satisfaction: optional phone call helpfulness [ Time Frame: 4 weeks after treatment initiation ]
  • Caregiver experience: facilitators and barriers [ Time Frame: Week 18 ]

Central Contacts and Locations

Central contacts

Kristen Barbour, MD

619-613-0693kbarbour@scripps.edu

Locations

Scripps Research Translational Institute

Recruiting

San Diego, California, United States, 92130

Contacts

Kristen Barbour, MD

619-613-0693kbarbour@scripps.edu

More Information

Sponsor

Scripps Translational Science Institute

Last update posted

Sep 29, 2026

Last verified

Sep, 2026

Keywords

  • SLC6A1
  • GAT-1
  • developmental and epileptic encephalopathy
  • DEE
  • phenylbutyrate
  • glycerol phenylbutyrate
  • 4-phenylbutyrate
  • 4-PBA
  • Ravicti
  • myoclonic atonic epilepsy
  • myoclonic-astatic epilepsy
  • Doose syndrome
  • decentralized
  • decentralized clinical trial
  • site-less
  • remote clinical trial
  • remote
  • virtual clinical trial
  • virtual
  • direct-to-patient
  • nationwide
  • digital
  • site less

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-30. This information was provided to ClinicalTrials.gov by Scripps Translational Science Institute on 2026-09-29. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.