[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100658158":3},{"organization":4,"outcomesModule":7,"designInfo":129,"detailedDescription":136,"studyPopulation":128,"armGroups":137,"interventions":149,"overallOfficials":155,"centralContacts":160,"locations":165,"responsibleParty":182,"collaborators":185,"id":189,"slug":190,"hasResults":191,"nctId":192,"briefTitle":193,"officialTitle":194,"acronym":128,"eligibilityCriteria":195,"healthyVolunteers":191,"sex":196,"minAge":197,"maxAge":198,"enrollmentInfo":199,"targetDuration":128,"studyType":202,"phases":203,"briefSummary":205,"conditions":206,"keywords":208,"overallStatus":168,"whyStopped":128,"lastUpdateSubmitDate":231,"lastUpdatePostDateStruct":232,"startDateStruct":235,"completionDateStruct":237,"leadSponsor":239,"locationsCount":240},{"fullName":5,"class":6},"Scripps Translational Science Institute","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":70,"otherOutcomes":128},[9,13,17,21,25,29,33,36,39,42,45,48,51,54,57,60,63,67],{"measure":10,"description":11,"timeFrame":12},"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)",{"measure":14,"description":15,"timeFrame":16},"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",{"measure":18,"description":19,"timeFrame":20},"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",{"measure":22,"description":23,"timeFrame":24},"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",{"measure":26,"description":27,"timeFrame":28},"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",{"measure":30,"description":31,"timeFrame":32},"Retention","Proportion of enrolled participants completing the 18-week assessment period without voluntary or involuntary withdrawal. Target: ≥80%.","Week 18",{"measure":34,"description":35,"timeFrame":32},"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.",{"measure":37,"description":38,"timeFrame":32},"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%.",{"measure":40,"description":41,"timeFrame":32},"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.",{"measure":43,"description":44,"timeFrame":32},"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.",{"measure":46,"description":47,"timeFrame":32},"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.",{"measure":49,"description":50,"timeFrame":32},"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\u002Fhelpful, 5=extremely clear\u002Fhelpful). Target: median ≥4.",{"measure":52,"description":53,"timeFrame":32},"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.",{"measure":55,"description":56,"timeFrame":32},"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.",{"measure":58,"description":59,"timeFrame":32},"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.",{"measure":61,"description":62,"timeFrame":32},"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.",{"measure":64,"description":65,"timeFrame":66},"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",{"measure":68,"description":69,"timeFrame":32},"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.",[71,75,78,81,85,89,92,95,98,101,104,107,110,113,117,121,125],{"measure":72,"description":73,"timeFrame":74},"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.","Baseline through week 18",{"measure":76,"description":77,"timeFrame":74},"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.",{"measure":79,"description":80,"timeFrame":32},"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.",{"measure":82,"description":83,"timeFrame":84},"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.","Baseline and week 18",{"measure":86,"description":87,"timeFrame":88},"Behavior: Aberrant Behavior Checklist Community Version","Change in total score and subscale scores (Irritability\u002FAgitation, Lethargy\u002FSocial Withdrawal, Stereotypic Behavior, Hyperactivity\u002FNoncompliance, Inappropriate Speech) from baseline to week 18. Total scores range 0-174; higher scores indicate more frequent or severe behavioral difficulties. Analyzed descriptively.","Baseline and Week 18",{"measure":90,"description":91,"timeFrame":84},"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.",{"measure":93,"description":94,"timeFrame":88},"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.",{"measure":96,"description":97,"timeFrame":24},"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.",{"measure":99,"description":100,"timeFrame":28},"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\u002FmL, phenylacetic acid-to-phenylacetylglutamine (PAA-to-PAGN) ratio \\> 1.5, bicarbonate level \\\u003C 17 mEq\u002FL, anion gap \\> 12 mEq\u002FL, urine pH \\\u003C 5.5, the combination of low carnitine (total carnitine level \\\u003C 30 µmol\u002FL OR free carnitine level \\\u003C 20 µmol\u002FL) 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.",{"measure":102,"description":103,"timeFrame":88},"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.",{"measure":105,"description":106,"timeFrame":88},"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.",{"measure":108,"description":109,"timeFrame":88},"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.",{"measure":111,"description":112,"timeFrame":88},"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.",{"measure":114,"description":115,"timeFrame":116},"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.","Week 6",{"measure":118,"description":119,"timeFrame":120},"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.","Weeks 0-2 and weeks 14-18",{"measure":122,"description":123,"timeFrame":124},"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.","Weeks 0-6 and weeks 12-18 of treatment",{"measure":126,"description":127,"timeFrame":16},"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.",null,{"allocation":130,"interventionModel":131,"interventionModelDescription":132,"primaryPurpose":133,"observationalModel":128,"timePerspective":128,"maskingInfo":134},"RANDOMIZED","PARALLEL","This study is a randomized, open-label, site-less (fully remote) feasibility trial evaluating phenylbutyrate for SLC6A1-related disorders using a delayed-start design.","TREATMENT",{"masking":135,"maskingDescription":128,"whoMasked":128},"NONE","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.\n\nSLC6A1-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.",[138,144],{"label":139,"type":140,"description":141,"interventionNames":142},"Arm A (Immediate Start)","EXPERIMENTAL","Arm A will receive immediate treatment with phenylbutyrate beginning week 0 through week 18.",[143],"Drug: Glycerol Phenylbutyrate",{"label":145,"type":146,"description":147,"interventionNames":148},"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.",[143],[150],{"type":151,"name":152,"description":153,"armGroupLabels":154,"otherNames":128},"DRUG","Glycerol Phenylbutyrate","Glycerol phenylbutyrate oral liquid (1.1 g\u002FmL) 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\u002Fm²\u002Fday to a target maximum of 11.2 mL\u002Fm²\u002Fday (12.4 g\u002Fm²\u002Fday), not to exceed 17.5 mL\u002Fday 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.\n\nOther Name(s): Ravicti; glycerol phenylbutyrate oral liquid; GPB; 4-phenylbutyrate; 4-PBA",[139,145],[156],{"name":157,"affiliation":158,"role":159},"Kristen Barbour, MD","This is a fully remote study. Participants may enroll from any U.S. state. No facility visit is required.","PRINCIPAL_INVESTIGATOR",[161],{"name":157,"role":162,"phone":163,"phoneExt":128,"email":164},"CONTACT","619-613-0693","kbarbour@scripps.edu",[166],{"facility":167,"status":168,"city":169,"state":170,"zip":171,"country":172,"countryCode":173,"cosmosGeoPoint":174,"geoPoint":179,"contacts":180},"Scripps Research Translational Institute","RECRUITING","San Diego","California","92130","United States","US",{"type":175,"coordinates":176},"Point",[177,178],-117.16472,32.71571,{"lat":178,"lon":177},[181],{"name":157,"role":162,"phone":163,"phoneExt":128,"email":164},{"type":159,"investigatorFullName":183,"investigatorTitle":184,"investigatorAffiliation":5,"oldNameTitle":128,"oldOrganization":128},"Kristen Barbour","Associate Physician",[186],{"name":187,"class":188},"National Center for Advancing Translational Sciences (NCATS)","NIH","100658158","phase-2-a-fully-remote-feasibility-trial-of-phenylbutyrate-for-slc6a1-related-disorders-100658158",false,"NCT07847918","A Fully Remote Feasibility Trial of Phenylbutyrate for SLC6A1-Related Disorders","A Site-Less Feasibility Trial of Phenylbutyrate for SLC6A1-Related Disorders","Inclusion Criteria:\n\n* Confirmed diagnosis of SLC6A1-related disorder based on a pathogenic or likely pathogenic variant in the SLC6A1 gene\n* Age 2-60 years at time of consent\n* Active clinical seizures, defined as ≥4 seizures in the 4 weeks prior to enrollment\n* Seizures persisting despite an adequate trial of ≥2 prior antiseizure medications at therapeutic doses\n* Stable antiseizure medication regimen for ≥4 weeks prior to enrollment\n* Parent, legal guardian, or legally authorized representative (LAR) able to provide informed consent and participate in digital follow-up assessments\n* Local licensed physician identified for ordering laboratory testing, EEG, and clinical evaluation as needed\n* English-speaking caregiver for consent and study communication\n\nExclusion Criteria:\n\n* Larger 3p25 chromosomal deletion extending beyond SLC6A1 and SLC6A11 to encompass additional genes\n* Early-infantile developmental and epileptic encephalopathy (DEE) phenotype\n* Epileptic spasms within the 6 months prior to enrollment\n* Hepatic impairment (AST or ALT \\>2× the upper limit of normal)\n* Renal impairment (eGFR \\\u003C60 mL\u002Fmin\u002F1.73m²)\n* Thrombocytopenia (platelet count \\\u003C150 × 10³\u002FμL)\n* Inborn errors of beta-oxidation\n* Pancreatic insufficiency or intestinal malabsorption\n* Known hypersensitivity to phenylbutyrate or any of its components\n* Participation in another interventional investigational study within 30 days or 5 half-lives of the investigational product, whichever is longer\n* Current use of alfentanil, quinidine, cyclosporine, or probenecid due to clinically significant interactions with phenylbutyrate based on CYP3A4 modulation\n* Pregnancy or breastfeeding\n* Any condition that in the investigator's judgment would interfere with study participation or safety monitoring\n\nThis is a fully remote study. Participants may enroll from any U.S. state. No facility visit is required.","ALL","2 Years","60 Years",{"count":200,"type":201},20,"ESTIMATED","INTERVENTIONAL",[204],"PHASE2","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.\n\nParticipants will be randomly assigned to one of two groups. Randomization is stratified by age band (\\\u003C7 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.\n\nParticipation 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.\n\nThis is a fully remote study. Participants may enroll from any U.S. state. No facility visit is required.",[207],"SLC6A1",[207,209,210,211,212,213,214,215,216,217,218,219,220,221,222,223,224,225,226,227,228,229,230],"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","2026-09-24",{"date":233,"type":234},"2026-09-29","ACTUAL",{"date":236,"type":201},"2026-10",{"date":238,"type":201},"2032-10",{"name":5,"class":6},1]