Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar

Bipolar Disorder Clinical Trial

Official title:

Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00176202
• Other study ID #: RIS-BIP-407
• Status: Completed
• Phase: Phase 3
• First received: September 9, 2005
• Last updated: November 4, 2015
• Start date: April 2003
• Est. completion date: January 2008

Study information

• Verified date: November 2015
• Source: University of Illinois at Chicago
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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:

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: January 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 20 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Drug:
• Divalproex Sodium
Divalproex sodium is a mood stabilizer
• risperidone
Risperidone is a second generation antipsychotic and antimanic drug

Locations

Country	Name	City	State
United States	Neuro Psychiatric Institute (NPI)	Chicago	Illinois
United States	NPI	Chicago	Illinois
United States	NPI, University of Illinois at Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Illinois at Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Young Mania Rating Scale (YMRS)	This measure has 11 items. The purpose of each item is to rate the severity of that abnormality in the patient. A severity rating is assigned to each of the eleven items, based on the patient's subjective report of his or her condition over the previous forty-eight hours and the clinician's behavioral observations during the interview, with the emphasis on the latter. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. Total score of zero to 60 is possible, zero being normal and 60 being severe, 12 serving as a cut off point for illness if equal or above. There are several ways to show change in outcome. We show the mean and standard deviation at week 0 and 6.	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).	No
Secondary	Child Depression Rating Scale- Revised (CDRS-R)	Response for depressive symptoms was defined as a score less than 40 on the CDRS-R. Range is 18 to 120. Score 18 is normal and higher score signifies depression. The Children's Depression Rating Scale (CDRS) is a 16-item measure used to determine the severity of depression in children 6-18 years of age. Items are measured on 3-, 4-, 5-, and 6-point scales. The mean and standard deviation are measured in this study to illustrate outcome at baseline and when the subject ended the study.	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).	No
Secondary	Child Mania Rating Scale (CMRS)	Child Mania rating scale is a parent rated measure to screen for symptoms of mania. It includes 21 items reflecting the DSM-IV criteria for a manic episode. Each item is answered on a four-point Likert type scale anchored by 0 (Never/Rare), 1 (Sometimes), 2 (Often), and 3 (Very Often). Maximum score possible is 63. Score higher than 20 is considered clinically significant, and this is a dimensional score of manic severity.	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).	No
Secondary	Clinical Global Improvement in Bipolar Disorder Overall (CGI-BP Overall)	Severity of Illness and Global Improvement are rated on a 7-point scale by the clinician. In addition to rating the overall illness with the CGI-BP, severity and improvement are considered on various other dimensions such as mania, depression, attention deficit/hyperactivity, psychosis, aggression and sleep difficulties. Score of 1, 2 and 3 would mean there is clinically observed symptom improvement where 1 is the best outcome than 2 or 3. The point 4 is the point where the subject presents at baseline of that specific individual. If they become worse on clinical symptoms, they are rated as 5, 6 or 7 where 7 is worse than 5.	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).	No