Clinical trial NCT00176202: Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar
Official title: Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder
Lead sponsor: University of Illinois at Chicago
Sponsor class: OTHER
First posted: 2005-09-15
Enrollment: 65
Sex: ALL
Minimum age (years): 10
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is to examine the null hypothesis that risperidone and divalproex sodium are equally effective in treating/stabilizing pediatric bipolar disorder.

Detailed description: Pediatric Bipolar Disorder (PBD) severely impairs a child's emotional development, and is associated with alarming rates of suicide, school failure, aggression, risk taking behaviors and substance abuse (Geller et al, 1998; 2001; Carlson et al, 1998). At present, very little is known about the pathophysiology or optimal treatment of PBD. The long range goals of this proposal are threefold: to investigate a range of pharmacotherapeutic agents that are safe and efficacious for PBD, to use fMRI techniques to examine abnormalities in brain function in this disorder, as well as any change in brain function after treatment.

In contrast to the adult literature, we are aware of only two prospective studies assessing the efficacy of standard mood stabilizers in a pediatric sample. In one, lithium was found to be moderately effective in PBD with comorbid substance abuse (Geller et al, 1998). In the other, divalproex sodium, lithium and carbamazepine produced a maximum of 50% symptom reduction (Kowatch et al, 2000). Subsequently, Kafantaris et al (2001) observed a potentiation of lithium's antimanic effect when combined with risperidone. Further, a prospective, open trial of olanzapine for PBD reported a 70% symptom reduction (Frazier et al, 2001) with a retention rate of 96% compared to only 7% with classic mood stabilizers (Kowatch et al, 2000).

Thus, parallelling adult studies (Sachs et al, 2000), novel antipsychotics are a promising treatment in this population. Further, up to 60% of acute PBD episodes present with psychotic features (Geller et al, in press). Finally, the time to full effect with mood stabilizers is often 4 weeks in children (Kowatch et al, 2000; Geller et al, 1998; Kafantaris et al, 2001), whereas antipsychotics usually have a more rapid response onset (Pavuluri et al, in press). Given the potential efficacy of novel antipsychotics for PBD, the aim is to conduct a randomized trial comparing a novel antipsychotic to a standard mood stabilizer:

Eligibility criteria: Inclusion Criteria:

* Children with Bipolar Disorder
* Must be able to swallow tablets

Exclusion Criteria:

* Children with general medical condition such as head injury, epilepsy, endocrine disorders
* Those who are on mood altering medications such as steroids, and those diagnosed with mental retardation are excluded to avoid confounding and contributing factors to mood swings.
* If we discover during the interview that the parent and/or child does not understand the consent/assent procedures, we will exclude them.

We expect only a small number of children to be excluded from the study due to exclusionary criteria. Selection of the subjects is not based on sex, race, or ethnic group.

Primary outcomes:
measure: Young Mania Rating Scale (YMRS)
timeFrame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point).
Secondary outcomes:
measure: Child Depression Rating Scale- Revised (CDRS-R)
timeFrame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point).
measure: Child Mania Rating Scale (CMRS)
timeFrame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point).
measure: Clinical Global Improvement in Bipolar Disorder Overall (CGI-BP Overall)
timeFrame: Six week study with assessment at baseline and end of the study (at the end of 6 weeks or earlier if they ended the study before 6 week end point).
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Neuro Psychiatric Institute (NPI)
state: Illinois
city: Chicago
country: United States
facility: NPI, University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: NPI
state: Illinois
Study officials:
affiliation: University of Ilinois at Chicago
name: Mani Pavuluri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pavuluri MN, Passarotti AM, Fitzgerald JM, Wegbreit E, Sweeney JA. Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):157-170.e5. doi: 10.1016/j.jaac.2011.10.019. Epub 2011 Dec 23.