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Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar

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ClinicalTrials.gov Identifier: NCT00176202
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : November 5, 2015
Last Update Posted : November 5, 2015
Sponsor:
Information provided by (Responsible Party):
Mani Pavuluri, University of Illinois at Chicago

September 9, 2005
September 15, 2005
June 2, 2015
November 5, 2015
November 5, 2015
April 2003
January 2008   (Final data collection date for primary outcome measure)
Young Mania Rating Scale (YMRS) [ Time Frame: 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). ]
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.
  • All subjects along with their parents will undergo
  • semi-structured interviews, and assessments for side effects. The following rating scales will be administered: the Young Mania Rating Scale (YMRS),
  • Bipolar Clinical Global Impression Scale (BP-CGI),
  • Overt Aggression Scale (OAS) ,
  • Child Depression Rating Scale-Revised (CDRS-R),
  • Brief Psychiatric Rating Scale in Children (BPRS-C),
  • Child Bipolar Rating Scale- Parent version (subscales: Child Mania Rating Scale,
  • Child Bipolar Depression Rating Scale,
  • Child Bipolar Cycling Rating Scale) and
  • Teacher version (subscales: Child Mania Rating Scale, Child Bipolar Depression Rating Scale)(CBRS-P/T),
  • Abnormal Involuntary Movements Scale (AIMS),
  • Adverse Events Rating Scale for Bipolar Disorder (AERS-BP) at the initial Screen, and every week for 6 weeks after starting the medication treatment.
Complete list of historical versions of study NCT00176202 on ClinicalTrials.gov Archive Site
  • Child Depression Rating Scale- Revised (CDRS-R) [ Time Frame: 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). ]
    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.
  • Child Mania Rating Scale (CMRS) [ Time Frame: 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). ]
    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.
  • Clinical Global Improvement in Bipolar Disorder Overall (CGI-BP Overall) [ Time Frame: 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). ]
    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.
Teachers will be asked to complete the Child Bipolar Rating Scale every week for 6 weeks
Not Provided
Not Provided
 
Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar
Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar
The study is to examine the null hypothesis that risperidone and divalproex sodium are equally effective in treating/stabilizing pediatric bipolar disorder.

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:

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Bipolar Disorder
  • Drug: Divalproex Sodium
    Divalproex sodium is a mood stabilizer
    Other Names:
    • antiepileptic
    • valproic acid
  • Drug: risperidone
    Risperidone is a second generation antipsychotic and antimanic drug
    Other Names:
    • antipsychotic
    • risperdal
  • Active Comparator: Risperidone
    Risperidone is an antimanic medication and is a second generation antipsychotic
    Intervention: Drug: risperidone
  • Active Comparator: Divalproex sodium
    Divalproex sodium is an antiepileptic medication and is a mood stabilizer
    Intervention: Drug: Divalproex Sodium
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
65
210
January 2008
January 2008   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
10 Years to 20 Years   (Child, Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00176202
RIS-BIP-407
Yes
Not Provided
Not Provided
Mani Pavuluri, University of Illinois at Chicago
University of Illinois at Chicago
Not Provided
Principal Investigator: Mani Pavuluri, MD University of Ilinois at Chicago
University of Illinois at Chicago
November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP