Clinical trial NCT03522168: Long-term Antipsychotic Pediatric Safety Trial
Official title: Pediatric Trials Network Long-term Antipsychotic Pediatric Safety Trial (LAPS) NICHD-2016-LAP01 Phase 4 Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Weight, Body
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: The Emmes Company, LLC
First posted: 2018-05-11
Enrollment: 509
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Main Study:

The study population will consist of two groups of children 3 - \<18 yrs old at the M0 visit:

* Risperidone group, n=350, including 30 children 3 - \<6 yrs old and 320 children 6 - \<18 yrs old, \~ 50% - 80% will have \<90 days of prior treatment with any antipsychotic.
* Aripiprazole group, n=350, including 30 children 3 - \<6 yrs old and 320 children 6 - \<18 yrs old., \~ 50% - 80% will have ≤90 days of prior treatment with any antipsychotic.

We will target participants within each treatment group to be distributed across the age range to permit analyses of age effects with:

* \~30 being 3 - \<6 years
* ≥35% (n ≥123) being 6 - \<12 years
* ≥35% (n ≥123) being 12 - \<18 years PK sub group at selected sites includes 24 participates, details in protocol.

Registry Sub-Study Registry participants will be selected exclusively from the population that has enrolled onto the LAPS Trial.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Main Study

Inclusion Criteria:

1. Parent/guardian has provided informed consent
2. Participant has provided assent if developmentally appropriate and as required by the institutional review board (IRB)
3. 3 - \<18 years of age inclusive at time of M0 visit
4. Participant, when developmentally appropriate, and parent/guardian are:

   1. Willing to authorize exchange of information between the SS and the participant's PPPMP and/or other significant medical provider
   2. Affirm participant's use at M0 visit of either risperidone or aripiprazole mono-antipsychotic therapy as prescribed by participant's PPPMP
5. 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:

   1. Participants ages 3 - \< 6 years can have any diagnosis and any dose
   2. 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
6. Guardian anticipates risperidone or aripiprazole treatment will continue for ≥6 months

Exclusion Criteria:

1. 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
2. Pre-existing or suspected major medical, metabolic, or genetic condition that is expected to be associated with weight, cardiovascular, neuromotor, or endocrine problems
3. Known or self-reported pregnancy
4. Taking antipsychotic medication other than either risperidone or aripiprazole at the time of M0 visit
5. Contraindications to participation in the study in the opinion of the SMC
6. Unwilling or unable to provide back-up family contact information

Registry Sub-Study

Inclusion Criteria:

1. Enrolled in LAPS Trial
2. 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
3. Parent/guardian/LAR/participant has provided informed consent
4. Participant has provided assent/consent if developmentally appropriate and as required by the institutional review board (IRB)
5. Participant was part of the 6 to \<18 year-old group in the LAPS Trial

Exclusion Criteria:

1. Participant has completed the M24 LAPS Trial Visit

Primary outcomes:
measure: Main Trial: Change in BMI z-score
timeFrame: Baseline, 24 months
measure: Registry Sub-Study: Modified Body Mass Index (BMI) z-score
timeFrame: Up to 24 months
Secondary outcomes:
measure: Main Trial: Measure of weight change
timeFrame: Baseline, 24 months
measure: Main Trial: Metabolic measures associated with risk of diabetes and cardiovascular disease
timeFrame: Baseline, 24 months
measure: Main Trial: Prolactin related outcomes
timeFrame: Baseline, 24 months
measure: Main Trial: Uniformly Elicited Events of Special Interest
timeFrame: Baseline, 24 months
measure: Main Trial: Adverse effects
timeFrame: Baseline, 24 months
measure: Main Trial: Suicidality
timeFrame: Baseline, 24 months
measure: Main Trial: Neuromotor effects
timeFrame: Baseline, 24 months
measure: Main Trial: AEs (Adverse Events)
timeFrame: Baseline, 24 months
measure: Main Trial: Pediatric Quality of Life Inventory
timeFrame: Baseline, 24 months
measure: Main Trial: School and Work Questionnaire (SWQ)
timeFrame: Baseline, 24 months
measure: Main Trial: Caregiver Strain Questionnaire (CSQ)
timeFrame: Baseline, 24 months
measure: Main Trial: Delighted-Terrible Faces Scale (DTFS)
timeFrame: Baseline, 24 months
measure: Main Trial: PK CL/F
timeFrame: 24 months
measure: Main Trial: PK Vss/F
timeFrame: 24 months
measure: Main Trial: PK AUCss
timeFrame: 24 months
measure: Main Trial: PK Cmax
timeFrame: 24 months
measure: Main Trial: PK Tmax
timeFrame: 24 months
measure: Main Trial: PK T1/2
timeFrame: 24 months
measure: Registry Sub-Study: Parent/guardian/former guardian/LAR completed Pediatric Quality of Life Inventory (PedsQL, 23 item) survey.
timeFrame: Up to 24 months
Other outcomes:
measure: Registry Sub-Study: Weight and height
timeFrame: Up to 24 months
measure: Registry Sub-Study: Demographics, Measurements and Vital Signs, Lab Measurements, Clinical data
timeFrame: Up to 24 months
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Phoenix
country: United States
facility: Southwest Autism Research & Resource Center
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Research Institute
state: Arkansas
city: Lancaster
country: United States
facility: OM Research
state: California
city: Los Angeles
country: United States
facility: UCLA Semel Institute
state: California
city: New Haven
country: United States
facility: Yale Child Study Center
state: Connecticut
city: Miami
country: United States
facility: Clinical Trials Solution
state: Florida
city: Miami
country: United States
facility: South Florida Behavioral Health Network
state: Florida
city: North Miami
country: United States
facility: Scientific Clinical Research, Inc.
state: Florida
city: Columbus
country: United States
facility: Valley Healthcare System
state: Georgia
city: Grayson
country: United States
facility: IACT Health
state: Georgia
city: Smyrna
country: United States
facility: Attalla Consultants LLC dba Institute for Behavioral Medicine
state: Georgia
city: Naperville
country: United States
facility: AMR-Baber Research, Inc.
state: Illinois
city: South Bend
country: United States
facility: Beacon Medical Group
state: Indiana
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Lexington
country: United States
facility: Massachusetts General Hospital, Lurie Center for Autism
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Bloomfield
country: United States
facility: Neurobehavioral Medicine Group
state: Michigan
city: Grand Rapids
country: United States
facility: Pine Rest Christian Mental Health Services
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Bronx
country: United States
facility: Montefiore Medical Center, Albert Einstein College of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke Child and Family Study Center
state: North Carolina
city: Greensboro
country: United States
facility: Behavioral Health Hospital Oupatient Clinic
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Outpatient Behavioral Health
state: North Carolina
city: Raleigh
country: United States
facility: Carolina Partners in Mental HealthCare, PLLC
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Sioux Falls
country: United States
facility: Avera McKennan University Psychiatry Associates
state: South Dakota
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Austin
country: United States
facility: BioBehavioral Research of Austin
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Woodstock
country: United States
facility: Neuropsychiatric Associates
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Duke Clinical Research Institution (DCRI)
name: Linmarie Sikich, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Kevin Watt, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke Clinical Research Institution (DCRI)
name: Karan Kumar, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: