Characterization and Sequential Pharmacotherapy of Severe Mood Dysregulation
This project will characterize children and adolescents with severe mood dysregulation (SMD) and conduct a pilot study of combination pharmacotherapy as a basis for future intervention trials.
Eligible participants assessed for SMD will have 4 weeks open titration with lisdexamfetamine (LDX) to optimal dose, followed by double-blind randomization to fluoxetine (N=25) or placebo (N=25) in combination with optimized LDX for an additional 8 weeks. Participants will be monitored for clinical response and adverse events.
Specific aims are:
#1: To define youth meeting SMD criteria in terms of psychiatric comorbidity, neurocognitive functioning, and a potential "bio-signature" derived from electroencephalography (EEG).
Specific hypotheses to be tested include: 1) that SMD participants will differ in comparison to non-SMD individuals in our pre-existing database on patterns of a) psychiatric comorbidity, b) symptoms, c) behavioral ratings, and d) neurocognitive functioning, and 2) that a distinct EEG bio-signature will be confirmed in individuals formally diagnosed with SMD.
#2: To conduct a preliminary study of sequential pharmacotherapy for SMD with a stimulant followed by randomized, placebo-controlled selective serotonin re-uptake inhibitor (SSRI) therapy to evaluate the feasibility of recruitment and enrollment and assess the suitability of the proposed combination treatment as a basis for future clinical investigations.
Specific hypotheses to be tested include: 1) that significant improvement in Clinical Global Impression - Improvement -SMD (CGI-I-SMD) scores and other secondary measures are evident after open-label LDX titration; 2) that participants randomized to fluoxetine will demonstrate additional significant improvement in CGI-I-SMD scores and other secondary measures in comparison to participants randomized to placebo; 3) that combination LDX and SSRI therapy is safe and well tolerated, and 4) that EEG profiles will normalize with treatment.
|Severe Mood Dysregulation||Drug: lisdexamfetamine Drug: Placebo Drug: fluoxetine||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Characterization and Sequential Pharmacotherapy of Severe Mood Dysregulation|
- Clinical Global Impression-Improvement-Severe Mood Dysregulation [ Time Frame: Change from baseline at 12 weeks. ]A categorical clinician rating of overall improvement from baseline, modified by the National Institute of Mental Health to assess specific domains pertinent to Severe Mood Dysregulation.
- Pediatric Anxiety Rating Scale (PARS) [ Time Frame: Change from baseline to weeks 4 -12. ]A dimensional rating of pediatric anxiety symptoms designed for NIMH trials
- Children's Depression Rating Scale [ Time Frame: Change from baseline to weeks 4-12. ]A dimensional rating of depressive symptoms validated for children and adolescents.
- ADHD-IV Rating Scale [ Time Frame: Change from baseline at week 4. ]A dimensional rating of ADHD symptoms.
- ADHD IV Rating Scale [ Time Frame: Change from baseline at week 12. ]A dimensional measure of ADHD symptoms.
- Columbia Suicide Severity Scales [ Time Frame: Change from baseline at weeks 4-12. ]A structured assessment of suicidal ideation and activity.
- Barnes Akathisia Scale [ Time Frame: Change from baseline at weeks 4-12. ]A dimensional measure of abnormal movements and akathisia based on physical examination.
- Children's Affective Lability Scale [ Time Frame: Change from baseline at weeks 4-12. ]A parent completed measure of emotional reactivity.
- Physical Symptom Checklist [ Time Frame: Changes from baseline at weeks 1-12. ]A structured parent completed checklist of side effects commonly occurring with stimulant and SSRI therapy.
- Revised Modified Overt Aggression Scale [ Time Frame: Change from baseline at weeks 4-12. ]A parent rated retrospective assessment of oppositional and aggressive behaviors
- Screen for Children's Affective Reactivity [ Time Frame: Change from baseline at weeks 4-12. ]A parent completed measure of children's emotional reactivity.
- Affective Reactivity Index [ Time Frame: Change from baseline at weeks 4 to 12. ]A dimensional measure of emotional reactivity.
- Electroencephalography (EEG) [ Time Frame: Changes from baseline at week 12. ]EEG profiles of cortical activity.
|Study Start Date:||January 2013|
|Study Completion Date:||June 2016|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: lisdexamfetamine, fluoxetine
Open treatment with lisdexamfetamine with blinded treatment with fluoxetine beginning at visit 4.
Titration and open label treatment for 12 week study.
Other Name: VyvanseDrug: fluoxetine
Placebo Comparator: lisdexamfetamine, placebo
Open treatment with lisdexamfetamine with blinded treatment with placebo beginning at visit 4.
Titration and open label treatment for 12 week study.
Other Name: VyvanseDrug: Placebo
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01714310
|United States, California|
|UCLA Semel Institute|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||James J McGough, M.D.||University of California, Los Angeles|