Characterization and Sequential Pharmacotherapy of Severe Mood Dysregulation

Summary

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.

Conditions

• Severe Mood Dysregulation

Interventions

DRUG

lisdexamfetamine

Titration and open label treatment from baseline visit for 12 week study.

DRUG

Placebo

Initiated at end of study week 4 and continued to study week 12.

DRUG

fluoxetine

Initiated at end of study week 4 and continued to study week 12.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  collaborator NIH

• Shire

  collaborator INDUSTRY

• University of California, Los Angeles

  lead OTHER

Principal Investigators

• James J McGough, M.D. · University of California, Los Angeles

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

7 Years

Max Age

17 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-01-31

Primary Completion

2016-06-30

Completion

2016-06-30

Countries

• United States

Study Locations