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

NCT07847918 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: SRTI-GPBK12TR004410
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (18)

• Recruitment efficiency

  Number of participants enrolled and time from first contact to consent, averaged across the enrollment period. Target: ≥20 participants enrolled over 24 months.

  From study opening through end of enrollment (approximately 2 years)

• Protocol adherence: seizure diary completion

  Proportion of weekly seizure diary entries completed at scheduled intervals across the 18-week assessment period. Target: ≥80% of scheduled entries completed.

  Weeks 0-18

• Protocol adherence: Electroencephalogram (EEG) completion

  Proportion of participants completing baseline, week 6, and 18-week EEG as specified by protocol. Target: ≥80%.

  Baseline, week 6 and week 18

• Protocol adherence: side effect questionnaire completion

  Proportion of scheduled side effect questionnaires completed at protocol-specified intervals from treatment initiation through week 18. Target: ≥80%.

  From treatment initiation through week 18

• Protocol adherence: safety laboratory completion

  Proportion of participants completing scheduled safety laboratory testing at 6 weeks after treatment initiation. Target: ≥80%.

  6 weeks after treatment initiation

• Retention

  Proportion of enrolled participants completing the 18-week assessment period without voluntary or involuntary withdrawal. Target: ≥80%.

  Week 18

• Caregiver satisfaction: overall satisfaction

  Median score on User Experience Questionnaire item Q1 assessing overall satisfaction with remote clinical trial participation. Scale 1-5 (1=very dissatisfied, 5=very satisfied). Target: median ≥4.

  Week 18

• Caregiver satisfaction: acceptability

  Proportion of caregivers responding "Yes" to User Experience Questionnaire item Q2 asking whether they would recommend participating in a remote clinical trial to other families. Target: ≥80%.

  Week 18

• Caregiver satisfaction: fit with daily routine

  Median score on User Experience Questionnaire item Q3 assessing whether the study fit well into the family's daily routine. Scale 1-5 (1=not at all, 5=completely). Target: median ≥4.

  Week 18

• Caregiver satisfaction: clarity of study procedures

  Median score on User Experience Questionnaire item Q4 assessing ease of understanding study procedures and requirements. Scale 1-5 (1=very difficult, 5=very easy). Target: median ≥4.

  Week 18

• Caregiver satisfaction: time burden

  Median score on User Experience Questionnaire item Q5 assessing ease of finding time to complete study tasks. Scale 1-5 (1=very difficult, 5=very easy). Target: median ≥4.

  Week 18

• Caregiver satisfaction: study team communication

  Median score on User Experience Questionnaire item Q6 assessing clarity and helpfulness of study team communication. Scale 1-5 (1=not at all clear/helpful, 5=extremely clear/helpful). Target: median ≥4.

  Week 18

• Caregiver satisfaction: adequacy of remote safety monitoring

  Median score on User Experience Questionnaire item Q7 assessing whether the participant's safety was adequately monitored during the remote trial. Scale 1-5 (1=not at all, 5=completely). Target: median ≥4.

  Week 18

• Caregiver satisfaction: access to medical support

  Median score on User Experience Questionnaire item Q8 assessing ease of accessing medical support or advice when needed. Scale 1-5 (1=very difficult, 5=very easy). Target: median ≥4.

  Week 18

• Caregiver satisfaction: Research Electronic Data Capture (REDCap) usability

  Median score on User Experience Questionnaire item Q9 assessing comfort using the REDCap platform for study participation. Scale 1-5 (1=very uncomfortable, 5=very comfortable). Target: median ≥4.

  Week 18

• Caregiver satisfaction: instructional video usefulness

  Median score on User Experience Questionnaire item Q10 assessing usefulness of instructional videos provided through REDCap. Scale 1-5 (1=not at all useful, 5=extremely useful). Target: median ≥4.

  Week 18

• Caregiver satisfaction: optional phone call helpfulness

  Median score on User Experience Questionnaire item Q12 among participants who participated in the optional phone call at 4 weeks after treatment initiation (Q11=Yes). Scale 1-5 (1=not at all helpful, 5=extremely helpful). Proportion participating reported separately. Target: median ≥4 among participants.

  4 weeks after treatment initiation

• Caregiver experience: facilitators and barriers

  Thematic summary of free-text responses to User Experience Questionnaire items Q13 (what participants liked most) and Q14 (challenges faced). Analyzed qualitatively to identify themes relevant to remote trial design.

  Week 18

Secondary Outcomes (17)

• Seizure frequency: percent change from baseline

  Baseline through week 18

• Seizure frequency: responder rate

  Baseline through week 18

• Caregiver Global Impression of Change (CGIC)

  Week 18

• Adaptive behavior: Vineland Adaptive Behavior Scales, Third Edition (VABS-3) composite score

  Baseline and week 18

• Behavior: Aberrant Behavior Checklist Community Version

  Baseline and Week 18

Study Arms (2)

Arm A (Immediate Start)

EXPERIMENTAL

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

Drug: Glycerol Phenylbutyrate

Arm B (Delayed Start)

ACTIVE COMPARATOR

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

Drug: Glycerol Phenylbutyrate

Interventions

Glycerol Phenylbutyrate DRUG

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

Arm A (Immediate Start); Arm B (Delayed Start)

Eligibility Criteria

• Age: 2 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS): collaborator
• Scripps Translational Science Institute: lead

Study Sites (1)

Scripps Research Translational Institute

San Diego, California, 92130, United States

RECRUITING

MeSH Terms

Conditions

Epilepsies, Myoclonic

Interventions

glycerol phenylbutyrate

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Study Officials

• Kristen Barbour, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen Barbour, MD

CONTACT

619-613-0693; kbarbour@scripps.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

Model Details: This study is a randomized, open-label, site-less (fully remote) feasibility trial evaluating phenylbutyrate for SLC6A1-related disorders using a delayed-start design.

Study Record Dates

• First Submitted: April 9, 2026
• First Posted: September 29, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): October 1, 2032
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)