Asperger Syndrome, Autistic Disorder, Bipolar I Disorder, Bipolar II Disorder, Child Development Disorders, Pervasive, Mood Disorder NOS, Psychosis NOS, Schizoaffective Disorder, Schizophrenia, Schizophreniform Disorder, Severe Major Depression With Psychotic Features, Severe Mood Disorder With Psychotic Features, Single Episode Major Depression Without Psychotic Symptoms
Conditions
Keywords
Latuda,lurasidone,antipsychotics,autism, mood, psychosis
Brief summary
The overarching purpose of this pilot study is to collect preliminary data regarding the variability of weight gain associated with lurasidone (Latuda©) treatment of antipsychotic naive children and adolescents in order to inform decisions about including a lurasidone arm in a future large scale trial of different approaches to minimize antipsychotic associated weight gain in the pediatric population. In adults, lurasidone appears to cause minimal weight gain. The participants will be 6-19 years old with psychotic spectrum, mood spectrum, or autism spectrum disorders. They will have 4 weeks or less of lifetime antipsychotic exposure.
Detailed description
This is a multi-site, 12-week, open-label study assessing the weight and metabolic changes associated with lurasidone treatment. Antipsychotic (AP) naive subjects will start open-label treatment by following a flexible titration schedule. Quasi-antipsychotic naive subjects (less than 4 weeks of total AP treatment) will be started on lurasidone and tapered off the other antipsychotic over an estimated 4 weeks depending on the dose and tolerability of the prior antipsychotic. Other psychoactive medications including antidepressants, benzodiazepines, stimulants, alpha-2 agonists, and mood stabilizers are allowed as long as the dose is not changed, unless it is clinically necessary. Assessments of weight, efficacy, and side effects are conducted at baseline, week 2, week 4, week 8, and week 12. The primary outcome is percent change in weight. The secondary outcomes include psychiatric efficacy measures and side effects.
Interventions
DRUGLatuda©
All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant.
Sponsors
Foundation of Hope, North Carolina
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 19 Years
Healthy volunteers
No
Inclusion criteria
* Male and female children and adolescents between 6 and 19 years of age of any race or ethnicity * Subject must meet Diagnostic Statistical Manual (DSM)-IV-Text Revision (TR) criteria for a psychotic spectrum, mood spectrum or autism spectrum disorder as defined by one of the following diagnoses: * schizophrenia (any type) * schizoaffective disorder * schizophreniform disorder * psychosis Not Otherwise Specified (NOS) * autistic disorder with significant irritability/aggression (Aberrant Behavioral Checklist-Community (ABC-C) Irritability subscale score of greater than or equal to 18) * Asperger syndrome with significant irritability/aggression (ABC-C Irritability subscale score of greater than or equal to 18) * pervasive developmental disorder NOS with significant irritability/aggression (ABC-C Irritability subscale score of greater than or equal to 18) * bipolar type I * bipolar type II * mood disorder NOS * major depression with psychotic features * major depression (unresponsive to 2 different antidepressants) * severe mood dysregulation (SMD) according to Leibenluft and colleagues broad spectrum bipolar disorder * Subjects must have ≤ 4 weeks of lifetime exposure to an antipsychotic medication at any dosage. These medications include olanzapine (Zyprexa©), quetiapine (Seroquel©), risperidone (Risperdal©), ziprasidone (Geodon©), aripiprazole (Abilify©), asenapine (Saphris©), iloperidone (Fanapt©), lurasidone (Latuda©), haloperidol, chlorpromazine, perphenazine, fluphenazine, thiothixene, or clozapine * Subjects on other psychoactive medications are asked not to change dose of those medications during the course of the study unless clinically necessary * Sexually active girls must agree to use two effective forms of birth control (i.e. hormonal or spermicidal and barrier) or be abstinent) * Primary caretaker is able to participate in study appointments as is clinically indicated * Ability of child to participate in all aspects of the protocol per investigator's clinical judgment * After considering all aspects of study participation the subject (if an adult) or subject's parent or Legally Authorized Representative (LAR) must consent to participation * After considering all aspects of study participation, the subject must assent to participation if it is developmentally appropriate to obtain assent
Exclusion criteria
* Based on current or lifetime DSM-IV-TR criteria, a diagnosis of Eating Disorder (Anorexia Nervosa or Bulimia Nervosa) * Based on DSM-IV-TR criteria, a diagnosis of Substance Dependence Disorder (other than tobacco dependence) within the past month * Treatment with the following concomitant medications: strong CYP3A4 inhibitors (ex: Ketoconazole), strong CYP3A4 inducers (ex: Rifampin) * Current or past treatment with lurasidone (Latuda©) that resulted in a non-response or intolerance * Females who are pregnant or breast-feeding * Ongoing or previously undisclosed child abuse requiring new department of social service intervention * Subjects who, in the Investigator's opinion, might not be suitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weight | Baseline to 12 weeks | Change in weight from Baseline to Week 12 will be assessed as the primary outcome measure. Subjects will be asked to step on a special scale called a tanita which will calculate weight, fat mass at each study visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Completing Treatment | 12 weeks | Data will be collected on why participants terminated the study. If terminated early, the specific reason will be collected such as efficacy or tolerability. |
| Changes in Efficacy Measures | Baseline to 12 weeks | Efficacy measures included the Aberrant Behavior Checklist-Community (ABC-C) total score which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and social withdrawal. Differences in subdomains were not assessed. The ABC-C total score is the sum of 58 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC-C total score ranges from 0 to 174. Higher values of ABC-C total scores represent greater severity of illness. |
| Number of Participants Experiencing Side Effects | Baseline to12 weeks | Assessment of the medication side effects associated with lurasidone (Latuda©) in children and adolescents. |
| Overall Clinical Improvement | Baseline to 12 weeks | Overall psychiatric functioning will be assessed with the improvement (CGI-I) subscales of the CGI. CGI-I items are rated from 1 (very much improved) to 7 (very much worse). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Flexible Dose Latuda© Lurasidone (Latuda©)dose will be determined solely by the clinician in accordance with the best interests of each participant.
Latuda©: All subjects will be started on 20-40mg of Latuda© at night (suggested intake with food). Subsequently, the dose may be increased as clinically indicated and based on tolerability every 7 days by 20-40mg to a maximum of 160mg per day with food which may be given as a single or twice daily dose depending on participant's preference. The maintenance dose will be determined solely by the clinician in accordance with the best interests of each participant. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Flexible Dose Latuda© |
|---|---|
| Age, Continuous | 11.4 years STANDARD_DEVIATION 3.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 3 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Change in Weight
Change in weight from Baseline to Week 12 will be assessed as the primary outcome measure. Subjects will be asked to step on a special scale called a tanita which will calculate weight, fat mass at each study visit.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Flexible Dose Latuda© | Change in Weight | 0.70 lbs |
Secondary
Changes in Efficacy Measures
Efficacy measures included the Aberrant Behavior Checklist-Community (ABC-C) total score which focuses on problem behaviors in five subdomains, including irritability, attention, repetitive behaviors, unusual speech, and social withdrawal. Differences in subdomains were not assessed. The ABC-C total score is the sum of 58 items, each rated among 0 = Not at all; 1 = Slight in degree; 2 = Moderately serious; and 3 = Severe in degree. The ABC-C total score ranges from 0 to 174. Higher values of ABC-C total scores represent greater severity of illness.
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Flexible Dose Latuda© | Changes in Efficacy Measures | -14 units on a scale |
Secondary
Number of Participants Experiencing Side Effects
Assessment of the medication side effects associated with lurasidone (Latuda©) in children and adolescents.
Time frame: Baseline to12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flexible Dose Latuda© | Number of Participants Experiencing Side Effects | 3 Participants |
Secondary
Overall Clinical Improvement
Overall psychiatric functioning will be assessed with the improvement (CGI-I) subscales of the CGI. CGI-I items are rated from 1 (very much improved) to 7 (very much worse).
Time frame: Baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Flexible Dose Latuda© | Overall Clinical Improvement | 2.67 units on a scale | Standard Deviation 1.32 |
Secondary
Proportion of Participants Completing Treatment
Data will be collected on why participants terminated the study. If terminated early, the specific reason will be collected such as efficacy or tolerability.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Flexible Dose Latuda© | Proportion of Participants Completing Treatment | 7 Participants |