A Fully Remote Feasibility Trial of Phenylbutyrate for SLC6A1-Related Disorders
ConditionSLC6A1
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age2-60
SponsorScripps Translational Science Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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)
Trial design
Design model
Parallel
Treatments tested in this trial
Glycerol Phenylbutyrate
DrugGlycerol 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
Treatment groups
20 Participants
are divided into 2 treatment groupsGroup A: Arm A (Immediate Start)Experimental treatment 1 intervention
Group B: Arm B (Delayed Start)Active comparator 1 intervention
Trial outcomes
Primary outcomes
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.
Time frame
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.
Time frame
Weeks 0-183
Protocol adherence: Electroencephalogram (EEG) completion
Proportion of participants completing baseline, week 6, and 18-week EEG as specified by protocol. Target: ≥80%.
Time frame
Baseline, week 6 and week 184
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%.
Time frame
From treatment initiation through week 18Secondary outcomes
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.
Time frame
Baseline through week 182
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.
Time frame
Baseline through week 183
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.
Time frame
Week 184
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.
Time frame
Baseline and week 18Sponsors and contacts
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Scripps Translational Science Institute
Lead sponsor
National Center for Advancing Translational Sciences (NCATS)
Collaborator
Source ClinicalTrials.gov