A Phase 2A Open-Label Study Evaluating the Safety and Efficacy of Low-Dose Ketamine in Children With ADNP Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Number of Participants With an Adverse Event
研究概览
简要总结
This is a Phase 2A, single dose, open-label study to evaluate the safety, tolerability, and efficacy of a low-dose, 40-minute infusion into the veins (intravenous infusion or "IV") of ketamine in children with ADNP syndrome (Activity-Dependent Neuroprotective Protein). The study team will enroll 10 participants, ages 5 to 12, at Mount Sinai. The study participation is expected to last 4 weeks and will include 5 scheduled clinic visits in order to complete safety monitoring, clinical assessments, and biomarker collection. At the conclusion of this study, the study team expects to demonstrate the safety and tolerability of low-dose ketamine in children with ADNP syndrome. Additionally, the study team anticipates identifying meaningful signals of efficacy in clinical outcome measures using RNA and DNA sequencing to analyze ADNP protein expression and DNA methylation profiles, a natural process by which methyl groups are added to the DNA to change its activity, in order to assess sensitivity to change with low-dose ketamine treatment and inform future phase 3 studies. Ketamine is not currently approved by the Food and Drug Administration to treat this syndrome, but it is approved for use in children in other situations, for example in anesthesia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •5 to 12 years old (inclusive) at the time of informed consent;
- •Has a diagnosis of ADNP syndrome, confirmed by genetic testing prior to subject randomization;
- •Has a Clinical Global Impression-Severity score of 4 (moderately ill) or greater at screening;
- •Any concomitant medication, including anti-epileptic and/or behavioral medications, supplements, and special diets, must be at a stable dose for at least 4 weeks before;
- •Has an English-speaking caregiver capable of providing informed consent and able to attend all scheduled study visits, oversee the administration of study drug, and provide feedback regarding the subject's behavior and other symptoms as described in the protocol;
- •Provide assent to the protocol (when applicable);
- •Has a caregiver who will agree not to post any of the subject's personal medical data related to the study or information related to the study on any website or social media site (e.g., Facebook and Twitter) until they have been notified that the study is completed.
- •Age-specific blood pressure parameters for inclusion in the study will be based on established guidelines.
排除标准
- •Has a concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or any clinically significant finding at screening that could interfere with the conduct of the study or that would pose an unacceptable risk to the subject in this study;
- •Has clinically significant lab abnormalities or vital signs at the time of screening (e.g., alanine aminotransferase or aspartate aminotransferase >2.5 × upper limit of normal; total bilirubin or creatinine >1.5 × upper limit of normal). Re-testing of safety labs is allowed;
- •Hypertension that is not well controlled (systolic BP >130-140 mm Hg or diastolic BP >85-95 mm Hg depending on age);
- •A blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits;
- •Thyroid impairment, as reflected by a TSH > 4.2 mU/L;
- •Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac disease;
- •Has had changes in his/her medication regimen within the previous month;
- •Has a history of uncontrollable seizure disorder or seizure episodes within 1 month of screening;
- •Has a history of suicidal behavior or considered by the investigator to be at high risk of suicide;
- •Has a current or past history of psychotic symptoms;
- •Has enrolled in any clinical trial or used of any investigational agent, device, and/or investigational procedure within the 30 days before screening or does so concurrently with this study.
研究组 & 干预措施
Ketamine
Total dose administration or 0.5 mg/kg of ketamine
干预措施: Ketamine (Drug)
结局指标
主要结局
Number of Participants With an Adverse Event
时间窗: Week 4
Number of Participants with an adverse event as defined by the Systematic Longitudinal Assessment of Adverse Events (SLAES) which is a comprehensive form that assesses medical and behavioral conditions that were present at screening and/or baseline. Conditions are considered treatment emergent if their severity increased significantly after the participant had taken at least one dose of the study treatment. Treatment emergent adverse events will be tracked considered in the adverse event safety analysis. Severity of adverse events are categorized as mild, moderate, severe, life-threatening, or resulting in death and the treating physician indicates if the adverse event was related or unrelated to study drug.
次要结局
- Repetitive Behavior Scale-Revised (RBS-R)(Baseline, Week 1)
- Vineland Adaptive Behavior Scales(Baseline and Week 4)
- Anxiety, Depression and Mood Scales (ADAMS)(Baseline and Week 1)
- Aberrant Behavior Checklist(Baseline, Week 1)
- Peabody Picture Vocabulary Test and Expressive Vocabulary Test(Baseline, Week 1, Week 2, and Week 4)
- Proportion of Target-First Trials Saccades(Baseline, Day 1, Week 1)
- Latency to First Saccade(Baseline, Day 1, Week 1)
- Proportion of Target-Dwelling(Baseline, Day 1, Week 1)
- Electrophysiology Recording(Baseline, Week 1, Week 2, and Week 4)
- Caregiver Strain Questionnaire (CGSQ)(Baseline and Week 1)
- Clinical Global Impressions - Improvement Scale (CGI-I)(Baseline, Week 2, and Week 4)
- Childrens Sleep Habits Questionnaire(Baseline, Week 1)
研究者
Alexander Kolevzon
Professor
Icahn School of Medicine at Mount Sinai