Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mani Pavuluri, University of Illinois
ClinicalTrials.gov Identifier:
NCT00176202
First received: September 9, 2005
Last updated: June 20, 2013
Last verified: June 2013
  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 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar

Resource links provided by NLM:


Further study details as provided by University of Illinois at Chicago:

Primary Outcome Measures:
  • Young Mania Rating Scale (YMRS) [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Bipolar Clinical Global Impression Scale (BP-CGI) [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Overt Aggression Scale (OAS) [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Child Depression Rating Scale-Revised (CDRS-R) [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Brief Psychiatric Rating Scale in Children (BPRS-C) [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Child Bipolar Rating Scale- Parent version (subscales: Child Mania Rating Scale [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Child Bipolar Depression Rating Scale, [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Child Bipolar Cycling Rating Scale [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Teacher version (subscales: Child Mania Rating Scale, Child Bipolar Depression Rating Scale)(CBRS-P/T), [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Abnormal Involuntary Movements Scale (AIMS) [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • Adverse Events Rating Scale for Bipolar Disorder (AERS-BP) [ Time Frame: weekly ] [ Designated as safety issue: Yes ]

Enrollment: 65
Study Start Date: April 2003
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Risperidone, Divalproex Drug: Divalproex Sodium Drug: risperidone

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00176202

Locations
United States, Illinois
NPI
Chicago, Illinois, United States, 60612
Sponsors and Collaborators
University of Illinois at Chicago
Investigators
Principal Investigator: Mani Pavuluri, MD University of Ilinois at Chicago
  More Information

No publications provided

Responsible Party: Mani Pavuluri, Director of BRAIN Center, University of Illinois
ClinicalTrials.gov Identifier: NCT00176202     History of Changes
Other Study ID Numbers: RIS-BIP-407
Study First Received: September 9, 2005
Last Updated: June 20, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Risperidone
Valproic Acid
Anticonvulsants
Antimanic Agents
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 22, 2014