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Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar
This study is currently recruiting participants.
Verified by University of Illinois, April 2007
Sponsored by: University of Illinois
Information provided by: University of Illinois
ClinicalTrials.gov Identifier: NCT00176202
  Purpose

There are two purposes for this project. Study 1 is to determine whether risperidone is better than divalproex sodium in treating/stabilizing pediatric bipolar disorder. Study 2 is to look at the dysfunction in brain activity before treatment, and to look for any alteration after treatment with either risperidone or divalproex sodium. One initial part of Study 2 is looking at 10 healthy control adults to learn what areas of the brain are activated when the subject is exposed to faces showing different emotions, and when the subject is asked to determine emotionality, age, and recall of faces.


Condition Intervention Phase
Bipolar Disorder
Drug: Divalproex Sodium
Drug: risperidone
Phase II
Phase III

MedlinePlus related topics: Bipolar Disorder
Drug Information available for: Risperidone Divalproex sodium Valproate Sodium Valproic acid
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Efficacy Study
Official Title: Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar

Further study details as provided by University of Illinois:

Primary Outcome Measures:
  • 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.

Secondary Outcome Measures:
  • Teachers will be asked to complete the Child Bipolar Rating Scale every week for 6 weeks

Estimated Enrollment: 210
Study Start Date: April 2003
Estimated Study Completion Date: January 2008
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

Ages Eligible for Study:   10 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

For the fMRI study:

  • Given the limited size of the magnet bore, individuals with a body weight over two-hundred and fifty pounds will be unable to be tested within the MRI scanner.
  • Women in the latter stages of pregnancy may be excluded due to large body size and potential discomfort while in the MRI apparatus.
  • Standard contraindications for fMRI studies include: cardiac pacemaker, aneurysm clip, cochlear implants, shrapnel, history of metal fragments in eyes, claustrophobia
  • Participants with an IQ of less than 70 (assessed by WRAT) are likely to be excluded due to difficulties comprehending tasks and procedures.

Healthy Individuals/Controls:

  • Healthy participants will have full scale above 70
  • A negative family history of psychiatric treatment or diagnosis is necessary for healthy comparison participants
  • Individuals with a positive medical history of neurological disease, brain injury, and/or psychotic, mood, or substance abuse disorders will not be admitted
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00176202

Contacts
Contact: Melissa S Moss, BA 312-355-1911 mmoss@psych.uic.edu
Contact: Erin M Harral, BA 312-413-1710 eharral@psych.uic.edu

Locations
United States, Illinois
NPI Recruiting
Chicago, Illinois, United States, 60612
Contact: Mani Pavuluri, MD     312-413-1722     mpavuluri@psych.uic.edu    
Principal Investigator: Mani Pavuluri, MD            
Sponsors and Collaborators
University of Illinois
Investigators
Principal Investigator: Mani Pavuluri, MD University of Ilinois at Chicago
  More Information

Study ID Numbers: RIS-BIP-407
Study First Received: September 9, 2005
Last Updated: April 18, 2007
ClinicalTrials.gov Identifier: NCT00176202  
Health Authority: United States: Institutional Review Board

Study placed in the following topic categories:
Affective Disorders, Psychotic
Dopamine
Mental Disorders
Bipolar Disorder
Risperidone
Mood Disorders
Psychotic Disorders
Valproic Acid
Serotonin

Additional relevant MeSH terms:
Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Dopamine Antagonists
Enzyme Inhibitors
Antipsychotic Agents
Antimanic Agents
Pharmacologic Actions
Serotonin Antagonists
Serotonin Agents
Therapeutic Uses
GABA Agents
Dopamine Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on January 16, 2009