Long-term Antipsychotic Pediatric Safety Trial

NCT03522168 | Completed DMC FDA Drug

• 1 other identifier: Pro00084468
• Study Type: observational
• Target: 509
• Locations: 1 country
• Sites: 37

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.

Conditions

Weight, Body

Outcome Measures

Primary Outcomes (2)

• Main Trial: Change in BMI z-score

  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.

  Baseline, 24 months

• Registry Sub-Study: Modified Body Mass Index (BMI) z-score

  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

  Up to 24 months

Secondary Outcomes (19)

• Main Trial: Measure of weight change

  Baseline, 24 months

• Main Trial: Metabolic measures associated with risk of diabetes and cardiovascular disease

  Baseline, 24 months

• Main Trial: Prolactin related outcomes

  Baseline, 24 months

• Main Trial: Uniformly Elicited Events of Special Interest

  Baseline, 24 months

• Main Trial: Adverse effects

  Baseline, 24 months

Other Outcomes (2)

• Registry Sub-Study: Weight and height

  Up to 24 months

• Registry Sub-Study: Demographics, Measurements and Vital Signs, Lab Measurements, Clinical data

  Up to 24 months

Study Arms (2)

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.

Drug: Risperidone

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.

Drug: Aripiprazole

Interventions

Risperidone DRUG

Medications prescribed as standard of care for Schizophrenia, Bipolar mania/acute treatment of manic and mixed episodes associated with Bipolar I disorder, Tourette's disorder, persistent (chronic) motor or vocal tic disorder and Irritability associated with autistic disorder

Also known as: Risperdal

Risperidone group

Aripiprazole DRUG

Medications prescribed as standard of care for Schizophrenia, Bipolar mania/acute treatment of manic and mixed episodes associated with Bipolar I disorder, Tourette's disorder, persistent (chronic) motor or vocal tic disorder and Irritability associated with autistic disorder

Also known as: Abilify

Aripiprazole group

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• Parent/guardian has provided informed consent
• Participant has provided assent if developmentally appropriate and as required by the institutional review board (IRB)
• \<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)

You may not qualify if:

• 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
• 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
• \. Participant has completed the M24 LAPS Trial Visit

Sponsors & Collaborators

• Duke University: lead
• The Emmes Company, LLC: collaborator

Study Sites (37)

Harmonex Neuroscience Research

Dothan, Alabama, 36303, United States

Location

Southwest Autism Research & Resource Center

Phoenix, Arizona, 85006, United States

Location

Arkansas Children's Research Institute

Little Rock, Arkansas, 72202, United States

Location

OM Research

Lancaster, California, 93594, United States

Location

UCLA Semel Institute

Los Angeles, California, 90024, United States

Location

Yale Child Study Center

New Haven, Connecticut, 06520, United States

Location

Clinical Trials Solution

Miami, Florida, 33126, United States

Location

South Florida Behavioral Health Network

Miami, Florida, 33126, United States

Location

Scientific Clinical Research, Inc.

North Miami, Florida, 33161, United States

Location

Valley Healthcare System

Columbus, Georgia, 31903, United States

Location

IACT Health

Grayson, Georgia, 30017, United States

Location

Attalla Consultants LLC dba Institute for Behavioral Medicine

Smyrna, Georgia, 30082, United States

Location

AMR-Baber Research, Inc.

Naperville, Illinois, 60563, United States

Location

Beacon Medical Group

South Bend, Indiana, 46601, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital, Lurie Center for Autism

Lexington, Massachusetts, 02421, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Neurobehavioral Medicine Group

Bloomfield, Michigan, 48302, United States

Location

Pine Rest Christian Mental Health Services

Grand Rapids, Michigan, 49548, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68131, United States

Location

Montefiore Medical Center, Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke Child and Family Study Center

Durham, North Carolina, 27705, United States

Location

Behavioral Health Hospital Oupatient Clinic

Greensboro, North Carolina, 27278, United States

Location

Cone Health Outpatient Behavioral Health

Greensboro, North Carolina, 27403, United States

Location

Carolina Partners in Mental HealthCare, PLLC

Raleigh, North Carolina, 27609, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219-2492, United States

Location

Avera McKennan University Psychiatry Associates

Sioux Falls, South Dakota, 57108, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

BioBehavioral Research of Austin

Austin, Texas, 78759, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Neuropsychiatric Associates

Woodstock, Vermont, 05091, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Main Trial: Obtain whole blood samples for future genetic analyses that may be used to determine if there are any genetic factors that might be used to personalize risk assessments. Registry Sub-Study: None.

MeSH Terms

Conditions

Body Weight

Interventions

Risperidone; Aripiprazole

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Linmarie Sikich, MD

  Duke Clinical Research Institution (DCRI)

  PRINCIPAL INVESTIGATOR

• Kevin Watt, MD, PhD

  University of Utah

  PRINCIPAL INVESTIGATOR

• Karan Kumar, MD, MS

  Duke Clinical Research Institution (DCRI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Kiser-Arena Professor of Pediatrics

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 11, 2018
• Study Start: January 10, 2019
• Primary Completion: November 21, 2023
• Study Completion: November 21, 2023
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be uploaded to the repository within 2 years of study completion. It will be maintained in the repository indefinitely.
• Access Criteria: In order to have access, researchers have to complete a Data access request. NICHD will review the request and either approve or deny it. IRB approval must be obtained by the researcher to access the data. https://dash.nichd.nih.gov/Resource/DataRequestChecklist

Locations

US (37)