ClinicalTrials.gov
ClinicalTrials.gov Menu

Long-term Antipsychotic Pediatric Safety Trial (LAPS) (LAP01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03522168
Recruitment Status : Recruiting
First Posted : May 11, 2018
Last Update Posted : January 10, 2019
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
Kevin Watt, Duke University

Brief Summary:
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.

Condition or disease Intervention/treatment
Weight, Body Drug: Risperidone Drug: Aripiprazole

Detailed Description:
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 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, with the participant's PPPMP. 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.

Study Type : Observational
Estimated Enrollment : 700 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pediatric Trials Network Long-term Antipsychotic Pediatric Safety Trial (LAPS) NICHD-2016-LAP01 Phase 4 Trial
Estimated Study Start Date : January 30, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight

Group/Cohort Intervention/treatment
Risperidone group
Rispridone, 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
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
Other Name: Risperdal

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
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
Other Name: Abilify




Primary Outcome Measures :
  1. Change in BMI z-score [ Time Frame: 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.


Secondary Outcome Measures :
  1. Measure of weight change [ Time Frame: Baseline, 24 months ]
    Change in BMI category and Modified BMI z-score increase of ≥1.0 unit from M0

  2. Metabolic measures associated with risk of diabetes and cardiovascular disease [ Time Frame: Baseline, 24 months ]
    Clinical laboratory evaluations for high-sensitivity C-reactive protein (hs-CRP); hemoglobin A1c (Hgb A1c); Presence of acanthosis nigricans or, in females only, hirsuitism on physical exam

  3. Prolactin related outcomes [ Time Frame: Baseline, 24 months ]
    Clinical laboratory evaluation of serum prolactin; Incidence of gynecomastia in males on physical exam

  4. Uniformly Elicited Events of Special Interest [ Time Frame: Baseline, 24 months ]
    A standardized semi-structured interview will be used by the SMC to assess events of special interest in all participants at every in-person visit [56]. The form queries for potential hospitalizations, emergency department visits, and urgent care visits and for pregnancy. The form also evaluates frequent or especially concerning adverse effects seen with antipsychotics including behavioral events. Targeted symptoms are: Sedation, Increased sleep, Problems with attention, thinking or learning Insomnia, Arrhythmias, Light-headedness (Orthostasis vs Vertigo), Seizures, Increased appetite, Decreased appetite, Tics, Tremors, Parkinsonian symptoms, Akathisia, Drooling, Dyskinesia, Polydipsia, Polyuria, Enuresis, Galactorrhea, Amenorrhea, Sexual dysfunction/anorgasmia, Diabetes, Fractures Menorrhagia, Lack of satiety

  5. Adverse effects [ Time Frame: Baseline, 24 months ]
    Serious adverse events Adverse events (AEs) of mild (grade 1) severity and related to risperidone or aripiprazole All adverse events of moderate (grade 2) severity or greater regardless of relatedness to risperidone or aripiprazole

  6. Suicidality [ Time Frame: Baseline, 24 months ]
    Assessed using DASS

  7. Neuromotor effects [ Time Frame: Baseline, 24 months ]
    Abnormal Involuntary Movement Scale (AIMS) Simpson Angus Extrapyramidal Symptoms Scale (SAS)

  8. AEs (Adverse Events) [ Time Frame: Baseline, 24 months ]
    Elicited AEs, including AEs of mild (grade 1) and related to risperidone or aripiprazole, and all AEs of moderate (grade 2) or greater and clinically significant changes in suicidality.

  9. Benefits - Pediatric Quality of Life Inventory [ Time Frame: Baseline, 24 months ]
    Relationship of risperidone or aripiprazole therapy to adaptive functioning and quality of life as assessed by the Pediatric Quality of Life Inventory (PedsQL, 23 item), and changes in the intensity or frequency of pre-existing behavioral problems indicated at M0 (baseline). The 23-item PedsQL Generic Core Scales were designed to measure the core dimensions of health as delineated by the World Health Organization in individuals aged 2 years and older. The main scales include physical functioning, emotional functioning, social functioning, and school functioning. Summary scores can also be utilized to measure change over time on a five point scale for 0 = "Never a Problem" to 5 = "Almost Always a Problem". The guardian will be asked to complete the parent version for reporting on their child's quality of life.

  10. Benefit - School and Work Questionnaire (SWQ) [ Time Frame: Baseline, 24 months ]
    Relationship of risperidone or aripiprazole therapy with age-appropriate skip patterns, school promotions and graduations, changes in school supports, type of living situations, romantic relationships, arrests, and types and extent of employment during the interval since the prior assessment.

  11. Benefits- Caregiver Strain Questionnaire (CSQ) [ Time Frame: Baseline, 24 months ]
    Relationship of risperidone or aripiprazole therapy to adaptive functioning and quality of life as assessed ) by the Caregiver Strain Questionnaire (CSQ) and changes in the intensity or frequency of pre-existing behavioral problems indicated at M0 (baseline). This is a 21-item questionnaire with a categorical scale ranging from 1 (not at all a problem) to 5 (very much a problem) that assesses the caregiver's quality of life. It asks specifically about the caregiver's quality of life by assessing the impact of caring for a child with emotional and behavioral problems. The questions include information about disruption of family life and relationships; demands on time; negative, mental, and physical health effects for any family member; financial strain; feelings of sacrifice; disruption of social/community life; worry/guilt; fatigue/strain; and embarrassment.

  12. Benefits - Delighted-Terrible Faces Scale (DTFS) [ Time Frame: Baseline, 24 months ]
    Relationship of risperidone or aripiprazole therapy to adaptive functioning and quality of life as assessed by the Delighted-Terrible Faces Scale (DTFS) and changes in the intensity or frequency of pre-existing behavioral problems indicated at M0 (baseline). The DTFS is a uni-dimensional, single item scale that will be used to assess the participant's perceived life quality. Faces expressing various feelings are depicted, and the participant is asked which face comes closest to expressing how he/she feels about his/her life over the past month. The participant can then select from the range of seven categorical faces depicting from one-delighted to seven-terrible expressions. This scale is included because it can be easily completed by participants with limited verbal and cognitive abilities as well as by very young children.

  13. PK CL/F [ Time Frame: 24 months ]
    CL/F, apparent total clearance of the drug from plasma after oral administration at steady state

  14. PK Vss/F [ Time Frame: 24 months ]
    Vss/F, apparent volume of distribution at steady state after non-intravenous administration at steady state

  15. PK AUCss [ Time Frame: 24 months ]
    AUCss, area under the curve at steady state

  16. PK Cmax [ Time Frame: 24 months ]
    Cmax, maximum concentration at steady state

  17. PK Tmax [ Time Frame: 24 months ]
    Tmax, time of maximum concentration at steady state

  18. PK T1/2 [ Time Frame: 24 months ]
    T1/2, half-life at steady state


Biospecimen Retention:   Samples With DNA
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.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   3 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03522168


Contacts
Contact: Cheryl Alderman 919-668-8349 cheryl.alderman@duke.edu
Contact: Tedryl Bumpass 919.668.8798 tedryl.bumpass@duke.edu

Locations
United States, Alabama
Harmonex Neuroscience Research Recruiting
Dothan, Alabama, United States, 36303
Contact: Barbara Baldwin    334-836-2000    bbaldwin@harmonex.us   
Contact: Amellia Brackin    334-836-2000    abrackin@harmonex.us   
United States, Arkansas
Arkansas Children's Research Institute Recruiting
Little Rock, Arkansas, United States, 72202
Contact: Nicole McBride    501-364-4188    nmcbride@uams.edu   
Contact: Nihit Kumar    501-364-1992    nkumar@uams.edu   
United States, Florida
Scientific Clinical Research, Inc. Recruiting
North Miami, Florida, United States, 33161
Contact: Linda Cenci    305-722-8444    lcenci@segaltrials.com   
Contact: Jenny Rojas    305-722-8444    jrojas@segaltrials.com   
United States, Indiana
Beacon Medical Group Recruiting
South Bend, Indiana, United States, 46601
Contact: Stephanie Kuespert    574-647-6584    skuespert@beaconhealthsystem.org   
Contact: Toni Riehm    574-647-7883    triehm@beaconhealthsystem.org   
Sponsors and Collaborators
Duke University
The EMMES Corporation
Investigators
Study Chair: Linmarie Sikich, MD Duke Clinical Research Institution (DCRI)
Principal Investigator: Kevin Watt, MD, PhD Duke Clinical Research Institution (DCRI)
  Study Documents (Full-Text)

Documents provided by Kevin Watt, Duke University:
Study Protocol  [PDF] December 12, 2017


Responsible Party: Kevin Watt, Assistant Professor of Pediatrics, Duke University
ClinicalTrials.gov Identifier: NCT03522168     History of Changes
Other Study ID Numbers: Pro00084468
First Posted: May 11, 2018    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All data collected is uploaded into the National Institute of Health data repository (DASH) at the end of the study (de-identified).
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

URL: https://dash.nichd.nih.gov/

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Body Weight
Signs and Symptoms
Risperidone
Antipsychotic Agents
Aripiprazole
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents