A Site-Less Feasibility Trial of Phenylbutyrate for SLC6A1-Related Disorders
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Recruitment efficiency
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Glycerol Phenylbutyrate (Drug)
Arm A (Immediate Start)
Arm A will receive immediate treatment with phenylbutyrate beginning week 0 through week 18.
干预措施: Glycerol Phenylbutyrate (Drug)
结局指标
主要结局
Recruitment efficiency
时间窗: From study opening through end of enrollment (approximately 2 years)
Number of participants enrolled and time from first contact to consent, averaged across the enrollment period. Target: ≥20 participants enrolled over 24 months.
Protocol adherence: seizure diary completion
时间窗: Weeks 0-18
Proportion of weekly seizure diary entries completed at scheduled intervals across the 18-week assessment period. Target: ≥80% of scheduled entries completed.
Protocol adherence: Electroencephalogram (EEG) completion
时间窗: Baseline, week 6 and week 18
Proportion of participants completing baseline, week 6, and 18-week EEG as specified by protocol. Target: ≥80%.
Protocol adherence: side effect questionnaire completion
时间窗: From treatment initiation through week 18
Proportion of scheduled side effect questionnaires completed at protocol-specified intervals from treatment initiation through week 18. Target: ≥80%.
Protocol adherence: safety laboratory completion
时间窗: 6 weeks after treatment initiation
Proportion of participants completing scheduled safety laboratory testing at 6 weeks after treatment initiation. Target: ≥80%.
Retention
时间窗: Week 18
Proportion of enrolled participants completing the 18-week assessment period without voluntary or involuntary withdrawal. Target: ≥80%.
Caregiver satisfaction: overall satisfaction
时间窗: Week 18
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.
Caregiver satisfaction: acceptability
时间窗: Week 18
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%.
Caregiver satisfaction: fit with daily routine
时间窗: Week 18
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.
Caregiver satisfaction: clarity of study procedures
时间窗: Week 18
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.
Caregiver satisfaction: time burden
时间窗: Week 18
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.
Caregiver satisfaction: study team communication
时间窗: Week 18
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.
Caregiver satisfaction: adequacy of remote safety monitoring
时间窗: Week 18
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.
Caregiver satisfaction: access to medical support
时间窗: Week 18
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.
Caregiver satisfaction: Research Electronic Data Capture (REDCap) usability
时间窗: Week 18
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.
Caregiver satisfaction: instructional video usefulness
时间窗: Week 18
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.
Caregiver satisfaction: optional phone call helpfulness
时间窗: 4 weeks after treatment initiation
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.
Caregiver experience: facilitators and barriers
时间窗: Week 18
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.
次要结局
- 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)
- Quality of life: QI-Disability score(Baseline and week 18)
- Medication Burden(Baseline and Week 18)
- Safety and tolerability: adverse events(From treatment initiation through week 18)
- Safety and tolerability: laboratory values(6 weeks after treatment initiation)
- EEG: Delta spectral power(Baseline and Week 18)
- EEG: Delta-frequency autocorrelation(Baseline and Week 18)
- EEG: Spectral entropy(Baseline and Week 18)
- EEG: Combination of three measures(Baseline and Week 18)
- Concurrent randomized seizure comparison(Week 6)
- Arm A within-person early vs. stable dose seizure comparison(Weeks 0-2 and weeks 14-18)
- Arm B within-person seizure change(Weeks 0-6 and weeks 12-18 of treatment)
- Trajectory replication across arms(Weeks 0-18)
研究者
Kristen Barbour
Associate Physician
Scripps Translational Science Institute