Pediatric Trials Network Long-term Antipsychotic Pediatric Safety Trial (LAPS) NICHD-2016-LAP01 Phase 4 Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 509
- 试验地点
- 37
- 主要终点
- Main Trial: Change in BMI z-score
研究概览
简要总结
Main LAP01 study: The purpose is to evaluate the long-term pathologic weight changes associated with multi-year risperidone or aripiprazole therapy in 3 - <18-year-old children, who have varying durations of prior antipsychotic drug exposure from the start of study Month 0 (M0). This is critical because children appear to have greater vulnerability to antipsychotic-associated weight gain than adults, and obesity has significant effects on morbidity and mortality.
An additional sub-study (registry sub-study) was added via a protocol amendment. This registry sub-study is optional for participants and only participants who participate in the main study are eligible if they were 6 to less than 18 years of age at the time of the M0 visit. Participants who consent to this registry sub-study will participate in yearly in-person visits and complete monthly assessments remotely over the course of two additional years from the time of their final visit of the main LAP01 study.
详细描述
Main LAP01 study: Prospective, multi-site, Phase 4, longitudinal observational study designed to systematically collect robust longitudinal post-marketing safety and quality of life data about multi-year pediatric treatment with risperidone or aripiprazole. Screening may occur for up to 37 days prior to enrollment. Assessments will occur at in-person visits planned at months 0, 6, 12, 18 and 24, and at unscheduled, in-person visits that study staff request when the participant switches or stops antipsychotic monotherapy with risperidone or aripiprazole, adds or stops treatment with a weight modifying agent, becomes pregnant, chooses to withdraw from the study prematurely or, has an ongoing Serious Adverse Event (SAE) that requires further assessment. Monthly remote interim contacts occurring between in-person visits will monitor for changes (other than dose related) in antipsychotic therapy or weight modifying treatments, potential SAEs, and potential pregnancy. The participant, his/her parent/guardian, and the participant's personal psychotropic-prescribing medical provider (PPPMP) will make any and all decisions related to antipsychotic medications, any other medications, and the participant's current mental state, developmental/psychiatric condition, and level of risk for potential harm to self or others independent of the study procedures and assessments. Study staff (SS) will share with the participant's PPPMP all lab results and changes in the participant's AEs or clinical presentation, which the study medical clinician (SMC) considers medically concerning based on the participant's assessment during in-person visits. If an emergency safety concern is evident during an in-person visit, the SMC will immediately assess the participant, following medical standard-of-care procedures, to determine whether the participant is safe to leave the clinic or requires additional emergency care. If new or worsening symptoms are reported by the participant or parent/guardian during remote interim contacts, the participant and/or parent/guardian will be instructed to contact the PPPMP directly.
Registry sub-study: Participants who choose to participate will consent via a mobile application (Pattern Health) and will measure their height and weight at home monthly (also collected through the Pattern Health mobile application). One questionnaire will be completed every 6 months via the Pattern Health mobile application. Yearly in-person visits will be conducted to obtain in-clinic height, weight, vital signs and review concomitant medications.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 3 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parent/guardian has provided informed consent
- •Participant has provided assent if developmentally appropriate and as required by the institutional review board (IRB)
- •3 - <18 years of age inclusive at time of M0 visit
- •Participant, when developmentally appropriate, and parent/guardian are:
- •Willing to authorize exchange of information between the SS and the participant's PPPMP and/or other significant medical provider
- •Affirm participant's use at M0 visit of either risperidone or aripiprazole mono-antipsychotic therapy as prescribed by participant's PPPMP
- •Based on their age at the time of M0 visit, participant is receiving aripiprazole or risperidone at the dose and for the diagnoses as listed below:
- •Participants ages 3 - < 6 years can have any diagnosis and any dose
- •Participants ages ≥ 6 - <18 years at the doses and for the diagnoses listed below
- •Labeled Indications (Closely Related Disorders)
- •Aripiprazole 2-30 mg/day
- •Irritability associated with autistic disorder:
- •(Irritability in autism spectrum disorder) - Treatment of Tourette's disorder: (Tourette's disorder, persistent (chronic) motor or vocal tic disorder)
- •Bipolar mania/acute treatment of manic and mixed episodes associated with Bipolar l disorder: (Bipolar spectrum disorders including disruptive mood dysregulation disorder)
- •Schizophrenia: (Schizophrenia spectrum disorders including schizoaffective disorder, psychosis not otherwise specified, and delusional disorder)
- •Risperidone 0.25-6 mg/day - Irritability associated with autistic disorder: (Irritability in autism spectrum disorder)
- •Bipolar Mania: (Bipolar spectrum disorders including disruptive mood dysregulation disorder)
- •Schizophrenia: (Schizophrenia spectrum disorders including schizoaffective disorder, psychosis not otherwise specified, and delusional disorder)
- •MYCITE® (aripiprazole) and all forms of injectables are not permitted in this study
- •Guardian anticipates risperidone or aripiprazole treatment will continue for ≥6 months
排除标准
- •History of prior or current diagnosis of an eating disorder or meets diagnostic criteria for an eating disorder as described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and determined by psychiatric exam
- •Pre-existing or suspected major medical, metabolic, or genetic condition that is expected to be associated with weight, cardiovascular, neuromotor, or endocrine problems
- •Known or self-reported pregnancy
- •Taking antipsychotic medication other than either risperidone or aripiprazole at the time of M0 visit
- •Contraindications to participation in the study in the opinion of the SMC
- •Unwilling or unable to provide back-up family contact information
- •Registry Sub-Study
- •Inclusion Criteria:
- •Enrolled in LAPS Trial
- •Access to a personal mobile device (with Bluetooth capability and data or internet access) and willing to use it for the purposes of this study
- •Parent/guardian/LAR/participant has provided informed consent
- •Participant has provided assent/consent if developmentally appropriate and as required by the institutional review board (IRB)
- •Participant was part of the 6 to <18 year-old group in the LAPS Trial
- •Exclusion Criteria:
- •Participant has completed the M24 LAPS Trial Visit
研究组 & 干预措施
Risperidone group
Risperidone, n=350, including 30 children 3 - <6 years old and 320 children 6 - <18 years old. ~50% - ~80% of the entire group will have <90 days of prior treatment with any antipsychotic.
干预措施: Risperidone (Drug)
Aripiprazole group
Aripiprazole group, n=350, including 30 children 3 - <6 years old and 320 children 6 - <18 years old. ~50% - ~80% of the entire group will have ≤90 days of prior treatment with any antipsychotic.
干预措施: Aripiprazole (Drug)
结局指标
主要结局
Main Trial: Change in BMI z-score
时间窗: Baseline, 24 months
Longitudinally, evaluate the long term pathologic weight changes associated with multi- year risperidone or aripiprazole therapy over a period of 24 months in children ages 3 -\<18 years with varying durations of prior antipsychotic drug exposure at the M0 visit. The primary analysis will focus on changes in the modified Body Mass Index (BMI) z- score in children 6 - \<18 years old from M0 visit over 24 months of follow up.
Registry Sub-Study: Modified Body Mass Index (BMI) z-score
时间窗: Up to 24 months
Evaluate the long-term pathologic weight changes associated with multi-year risperidone or aripiprazole therapy over a period of 24 to 50 months in children who were 6 to \<18 years of age at the time of LAPS Trial enrollment
次要结局
- Main Trial: Measure of weight change(Baseline, 24 months)
- Main Trial: Prolactin related outcomes(Baseline, 24 months)
- Main Trial: AEs (Adverse Events)(Baseline, 24 months)
- Main Trial: Metabolic measures associated with risk of diabetes and cardiovascular disease(Baseline, 24 months)
- Main Trial: PK AUCss(24 months)
- Main Trial: PK Tmax(24 months)
- Registry Sub-Study: Parent/guardian/former guardian/LAR completed Pediatric Quality of Life Inventory (PedsQL, 23 item) survey.(Up to 24 months)
- Main Trial: Uniformly Elicited Events of Special Interest(Baseline, 24 months)
- Main Trial: Adverse effects(Baseline, 24 months)
- Main Trial: Suicidality(Baseline, 24 months)
- Main Trial: Neuromotor effects(Baseline, 24 months)
- Main Trial: PK CL/F(24 months)
- Main Trial: PK Cmax(24 months)
- Main Trial: PK T1/2(24 months)
- Main Trial: Pediatric Quality of Life Inventory(Baseline, 24 months)
- Main Trial: School and Work Questionnaire (SWQ)(Baseline, 24 months)
- Main Trial: Caregiver Strain Questionnaire (CSQ)(Baseline, 24 months)
- Main Trial: Delighted-Terrible Faces Scale (DTFS)(Baseline, 24 months)
- Main Trial: PK Vss/F(24 months)
研究者
Daniel Benjamin
Kiser-Arena Professor of Pediatrics
Duke University