NCT00221403

Brief Summary

The primary aim of this proposal is to conduct a preliminary controlled trial of valproate and risperidone in children ages 3-7 yr. with bipolar disorders. A secondary aim is to carefully characterize these subjects using clinical rating scales and develop pilot data on a very young cohort of children with bipolar disorders that can be used to support an application to NIMH for a prospective, longitudinal study that will provide important information about the course, medication response, neurobiology and outcome of these patients.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
46

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Sep 2004

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2004

Completed
1 year until next milestone

First Submitted

Initial submission to the registry

September 14, 2005

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 22, 2005

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2011

Completed
9.5 years until next milestone

Results Posted

Study results publicly available

October 20, 2020

Completed
Last Updated

October 20, 2020

Status Verified

September 1, 2020

Enrollment Period

6.7 years

First QC Date

September 14, 2005

Results QC Date

September 5, 2020

Last Update Submit

September 25, 2020

Conditions

Bipolar Disorder

Keywords

childadolescentbipolar disorder

Outcome Measures

Primary Outcomes (1)

  • YMRS

    Young Mania Rating Scale (YMRS) total scores change from baseline by treatment group. The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania, thus, a negative change (or decrease) from baseline indicates a reduction (or improvement) in manic symptoms.

    6 weeks

Study Arms (3)

Valproate (VPA)

ACTIVE COMPARATOR

VPA was administered in liquid form, matched for taste and color with the placebo. Medication was administered in a double-blinded manner on a twice-daily basis. Patients randomized to VPA were administered an initial dose of 10 mg/kg/day on a twice daily schedule beginning on day 0. VPA levels were adjusted to achieve a blood level of 80-100 lg/mL. An independent, unblinded study psychiatrist adjusted VPA doses to achieve a therapeutic level

Drug: Valproate Oral Solution

Risperidone

ACTIVE COMPARATOR

Risperidone was administered in liquid form matched for taste and color to the placebo. Medications were administered in a double-blinded manner on a twice-daily basis.

Drug: Risperidone oral solution

Placebo

PLACEBO COMPARATOR

The placebo was administered in liquid form, matched for taste and color with the active comparator.

Other: Placebo

Interventions

Risperidone oral solutionDRUG

liquid, BID dosing.

Also known as: Risperdal
Risperidone
Valproate Oral SolutionDRUG

liquid, BID dosing.

Also known as: VPA
Valproate (VPA)
PlaceboOTHER

liquid, BID dosing.

Placebo

Eligibility Criteria

Age3 Years - 7 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Male or female patients, 3-7 years 11 months of age.
  • Each patient's authorized legal guardian must understand the nature of the study and must provide written informed consent. Each patient must also give assent to study participation.
  • Patients must have a diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) bipolar disorder and must currently display an acute manic, hypomanic or mixed episode as determined by DSM-IV criteria. This includes the following diagnoses: 296.4x, Bipolar I Disorder, Most Recent Episode Manic; 296.6x, Bipolar I Disorder, Most recent Episode Mixed; and 296.0x, Bipolar I Disorder, Single Manic Episode, Bipolar II Disorder, Most Recent Episode Hypomanic.
  • Patients must have an initial score (at day 0) on the YMRS total score of at least 20.
  • Subjects and their caretakers should be fluent in English.

You may not qualify if:

  • Clinically significant or unstable hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical conditions.
  • Neurologic disorders including epilepsy, stroke, or severe head trauma.
  • Clinically significant laboratory abnormalities, on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, urinalysis, thyroid indices (T3, Total T4, Free T4, TSH), and EKG.
  • Mania due to a general medical condition or substance-induced mania (DSM-IV).
  • Mental retardation (IQ \<70), evidence of Fetal Alcohol Syndrome or an Alcohol-Related Neurodevelopmental Disorder.
  • History of hypersensitivity to or intolerance of risperidone or valproate.
  • Prior history of risperidone or valproate non-response.
  • Judged clinically to be at serious suicidal risk.
  • Participation in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry.
  • Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections and day 0.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45267, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53201, United States

Location

Related Publications (1)

  • Kowatch RA, Scheffer RE, Monroe E, Delgado S, Altaye M, Lagory D. Placebo-controlled trial of valproic Acid versus risperidone in children 3-7 years of age with bipolar I disorder. J Child Adolesc Psychopharmacol. 2015 May;25(4):306-13. doi: 10.1089/cap.2014.0166.

    PMID: 25978742RESULT

MeSH Terms

Conditions

Bipolar Disorder

Interventions

RisperidoneValproic Acid

Condition Hierarchy (Ancestors)

Bipolar and Related DisordersMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

PyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty Acids, VolatileFatty AcidsLipids

Limitations and Caveats

This study was limited by the small sample size and short duration of treatment. The average VPA level of 81 lg/ml was relatively low, and may have limited the response rate to VPA.

Results Point of Contact

Title
Robert Kowatch, MD, PhD
Organization
Ohio State Medical Center/Nationwide Children's Hospital
Robert.Kowatch@nationwidechildrens.org
(614) 355-2872

Study Officials

  • Robert A Kowatch, MD

    University of Cincinnati

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 14, 2005

First Posted

September 22, 2005

Study Start

September 1, 2004

Primary Completion

May 1, 2011

Study Completion

May 1, 2011

Last Updated

October 20, 2020

Results First Posted

October 20, 2020

Record last verified: 2020-09

Locations

US(2)