AzTrials
AzTrials

SLC6A1Phase 2NCT07847918

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

A Phase 2 study testing Glycerol Phenylbutyrate in people with SLC6A1, run by Scripps Translational Science Institute at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 2 to 60 years
Conditions the study is for
SLC6A1
What is being tested?
Glycerol Phenylbutyrate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Oct 2026to Oct 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 14Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kristen Barbour, MD contact

619-613-0693

kbarbour@scripps.edu

United States1 site, 1 recruiting
  • Scripps Research Translational Institute

    San Diego, California, 92130

    Kristen Barbour, MD, 619-613-0693, kbarbour@scripps.edu

    Recruiting

Other trials in United States

About this study

Official title: A Site-Less Feasibility Trial of Phenylbutyrate for SLC6A1-Related Disorders

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.

Read more

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.

Read the detailed description

The purpose of this study is to determine whether a site-less (fully remote) clinical trial design, one conducted entirely remotely without a physical clinic site, is feasible for families affected by SLC6A1-related disorders. A secondary purpose is to explore the safety, tolerability, and preliminary effectiveness of phenylbutyrate in this population.

SLC6A1-related disorder is a rare genetic condition that causes epilepsy and intellectual disability. It is caused by variants in the SLC6A1 gene, which encodes a protein called GABA transporter 1 (GAT-1) that helps regulate the brain chemical gamma-aminobutyric acid (GABA). Phenylbutyrate is a medication that is Food and Drug Administration (FDA) -approved for a different condition (urea cycle disorders) and is being studied here for its potential antiseizure effects in SLC6A1-related disorders. Early studies have suggested that phenylbutyrate may reduce seizure frequency in some individuals with this condition, but it has not yet been studied in a controlled clinical trial. This study will help determine whether a larger, controlled trial is feasible using a site-less (fully remote) design and will provide early information about how well phenylbutyrate works and how well it is tolerated in this population.

Conditions
SLC6A1
Being tested
Glycerol Phenylbutyrate
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
Medical subject headings
Epilepsies, Myoclonic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Glycerol PhenylbutyrateDrug

    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

Study groups in NCT07847918
Study groupRoleWhat they receive
Arm A (Immediate Start)ExperimentalArm A will receive immediate treatment with phenylbutyrate beginning week 0 through week 18.
Receives: Drug: Glycerol Phenylbutyrate
Arm B (Delayed Start)Active comparatorArm B will have a delayed start with an observation period weeks 0-6 followed by treatment beginning at week 6 through week 18.
Receives: Drug: Glycerol Phenylbutyrate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

    Measured: Weeks 0-18

  3. Protocol adherence: Electroencephalogram (EEG) completion

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

    Measured: Baseline, week 6 and week 18

  4. 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%.

    Measured: From treatment initiation through week 18

  5. Protocol adherence: safety laboratory completion

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

    Measured: 6 weeks after treatment initiation

  6. Retention

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

    Measured: Week 18

  7. 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.

    Measured: Week 18

  8. 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%.

    Measured: Week 18

  9. 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.

    Measured: Week 18

  10. 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.

    Measured: Week 18

  11. 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.

    Measured: Week 18

  12. 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.

    Measured: Week 18

  13. 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.

    Measured: Week 18

  14. 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.

    Measured: Week 18

  15. 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.

    Measured: Week 18

  16. 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.

    Measured: Week 18

  17. 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.

    Measured: 4 weeks after treatment initiation

  18. 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.

    Measured: Week 18

Secondary outcomes (17)
  1. Seizure frequency: percent change from baseline

    Percent change in average weekly seizure frequency from the baseline observation period to weeks 14-18 of treatment (stable dose period), based on caregiver-completed seizure diaries. Analyzed descriptively.

    Measured: Baseline through week 18

  2. Seizure frequency: responder rate

    Proportion of participants achieving ≥50% reduction in average weekly seizure frequency from baseline to the stable dose period (weeks 14-18 of treatment). Analyzed descriptively.

    Measured: Baseline through week 18

  3. Caregiver Global Impression of Change (CGIC)

    Caregiver-rated global impression of change since starting phenylbutyrate, assessed using a 7-point scale (1=very much improved, 7=very much worse). Analyzed descriptively.

    Measured: Week 18

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

    Change in VABS-3 Adaptive Behavior Composite score from baseline to week 18. Standard scores range 20-160; higher scores indicate better adaptive functioning. Analyzed descriptively.

    Measured: Baseline and week 18

  5. Behavior: Aberrant Behavior Checklist Community Version

    Change in total score and subscale scores (Irritability/Agitation, Lethargy/Social Withdrawal, Stereotypic Behavior, Hyperactivity/Noncompliance, Inappropriate Speech) from baseline to week 18. Total scores range 0-174; higher scores indicate more frequent or severe behavioral difficulties. Analyzed descriptively.

    Measured: Baseline and Week 18

  6. Quality of life: QI-Disability score

    Change in Quality of Life Inventory-Disability (QI-Disability) total score from baseline to week 18. Scores range 0-100; higher scores indicate better quality of life. Analyzed descriptively.

    Measured: Baseline and week 18

  7. Medication Burden

    Change in the number of concomitant antiseizure medications (not counting glycerol phenylbutyrate) from baseline to week 18, captured via weekly seizure diary. Analyzed descriptively.

    Measured: Baseline and Week 18

  8. Safety and tolerability: adverse events

    Frequency and severity of adverse events, serious adverse events, dose interruptions, and discontinuations throughout the study period. Summarized descriptively by event type, severity, causality, and outcome.

    Measured: From treatment initiation through week 18

  9. Safety and tolerability: laboratory values

    Proportion of 6 week post-treatment initiation safety laboratory values that are outside pre-specified thresholds reported descriptively, including phenylacetate level > 500 µg/mL, phenylacetic acid-to-phenylacetylglutamine (PAA-to-PAGN) ratio > 1.5, bicarbonate level < 17 mEq/L, anion gap > 12 mEq/L, urine pH < 5.5, the combination of low carnitine (total carnitine level < 30 µmol/L OR free carnitine level < 20 µmol/L) PLUS an elevated esterified-to-free carnitine ratio > 0.4, and ALT or AST (exceeds 3× the upper limit of normal with symptoms, or exceeds 5× the upper limit of normal without symptoms). Each parameter is reported separately as the proportion of participants with values outside pre-specified thresholds.

    Measured: 6 weeks after treatment initiation

  10. EEG: Delta spectral power

    Change in delta-frequency (2.5-4 Hz) EEG spectral power from baseline to week 18, calculated at 1-second intervals across 18 channel pairs in the double banana montage, averaged across channels and the analyzed epoch. Analyzed descriptively as an exploratory biomarker of treatment response.

    Measured: Baseline and Week 18

  11. EEG: Delta-frequency autocorrelation

    Change in EEG autocorrelation at lags corresponding to 2.5-4 Hz from baseline to week 18, calculated at 1-second intervals across 18 channel pairs in the double banana montage, averaged across channels and the analyzed epoch. Analyzed descriptively.

    Measured: Baseline and Week 18

  12. EEG: Spectral entropy

    Change in broadband (0-30 Hz) EEG spectral entropy from baseline to week 18, calculated at 1-second intervals across 18 channel pairs in the double banana montage, averaged across channels and the analyzed epoch. Analyzed descriptively.

    Measured: Baseline and Week 18

  13. EEG: Combination of three measures

    Proportion of 1-second EEG segments meeting all three pre-specified thresholds simultaneously (delta power >105,000 μV², autocorrelation >0.410, spectral entropy ≤3.16) in ≥3 channels, compared from baseline to week 18. Analyzed descriptively as an exploratory biomarker outcome.

    Measured: Baseline and Week 18

  14. Concurrent randomized seizure comparison

    Proportion of participants achieving ≥50% seizure reduction in Arm A (on treatment) versus Arm B (observation period) at week 6, reported as absolute risk difference, relative risk reduction, and number needed to treat, with 95% confidence intervals. Quantitative EEG measures (delta-frequency spectral power, autocorrelation at 2.5-4 Hz lags, and broadband spectral entropy) will be compared between arms at week 6 as an exploratory biomarker. Analyzed descriptively.

    Measured: Week 6

  15. Arm A within-person early vs. stable dose seizure comparison

    Mean weekly seizure frequency during early treatment (weeks 0-2) compared to the stable dose period (weeks 14-18) in Arm A participants. Analyzed descriptively.

    Measured: Weeks 0-2 and weeks 14-18

  16. Arm B within-person seizure change

    Seizure frequency trajectory in Arm B, estimated using a segmented regression model assessing whether the pre-treatment slope is flat and characterizing the post-treatment slope through the stable dose period (weeks 12-18). Analyzed descriptively.

    Measured: Weeks 0-6 and weeks 12-18 of treatment

  17. Trajectory replication across arms

    Comparison of post-treatment slopes from the segmented regression model in Arm A and Arm B, offset by 6 weeks, assessing whether the two arms show comparable seizure frequency trajectories following treatment initiation. Analyzed descriptively.

    Measured: Weeks 0-18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2026
  2. Study startOct 2026 (estimated)
  3. Primary completionMar 2029 (estimated)
  4. Study completionOct 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This study is a randomized, open-label, site-less (fully remote) feasibility trial evaluating phenylbutyrate for SLC6A1-related disorders using a delayed-start design.
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07847918
Sponsor's protocol ID
SRTI-GPB
Other IDs
K12TR004410
Status last verified
Sep 2026
First submitted
9 Apr 2026
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Glycerol Phenylbutyrate in people with SLC6A1, run by Scripps Translational Science Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kristen Barbour, MD (619-613-0693, kbarbour@scripps.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recruitment efficiency (time frame: From study opening through end of enrollment (approximately 2 years)). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in