Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00057681
First received: April 4, 2003
Last updated: March 27, 2013
Last verified: March 2013
Results First Received: May 29, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Bipolar Disorder
Interventions: Drug: Lithium carbonate
Drug: Valproate
Drug: Risperidone

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was from media advertisements and clinical referrals from 2003 to 2008. There were a total of N=379 subjects randomized to 1 of the 3 group strata. The strata were (1) medication-naive strategy, (2) add-on strategy, and (3) cross-taper strategy. Analyses have only been conducted on the N=279 subjects in the first stratum.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Randomized Medication - Lithium Participants will receive treatment with lithium for 8 to 16 weeks. At the initial dispensing visit, dose was 150mg qHS for 2 days, then 150mg BID for subjects <25kg; 150mg BID for 2 days, then 300mg BID for subjects 25-50kg; 300mg BID for 2 days, then 300mg AM / 600mg PM for subjects >50kg. Dose was adjusted to achieve blood levels of 0.8 mEq/L at week 1, 0.9-1.0 mEq/L at weeks 2-3, and 1.1-1.3 mEq/L at weeks 4-7.
Randomized Medication - Divalproex Sodium Participants will receive treatment with divalproex sodium for 8 to 16 weeks. At the initial dispensing visit, dose was 125mg qHS for 2 days, then 125mg BID for subjects <25kg; 250mg qHS for 2 days, then 125mg AM / 250mg PM for subjects 25-50kg; 250mg qHS for 2 days, then 250mg BID for subjects >50kg. Dose was adjusted to achieve blood levels of 75 ug/ml at week 1, 100-110 ug/ml at weeks 2-3, and 111-125 ug/ml at weeks 4-7.
Randomized Medication - Risperidone Participants will receive treatment with risperidone for 8 to 16 weeks. At the initial dispensing visit, dose was 0.25mg qHS for 2 days, then 0.25mg BID for subjects <25kg; 0.25mg BID for 2 days, then 0.5mg BID for subjects 25-50kg; 0.25mg BID for 2 days, then 0.5mg BID for subjects >50kg. Dose was adjusted at weeks 2-3 to 0.5mg BID for subjects <25kg, 1.0mg BID for subjects 25-50kg and >50kg. Dose was adjusted at weeks 4-5 to 1.0mg BID for subjects <25kg, 1.5mg BID for subjects 25-50kg, 2.0kg BID for subjects >50kg. Dose was adjusted at weeks 6-7 to 2.0mg BID for subjects <25kg, 2.0mg AM / 3.0mg PM for subjects 25-50kg, 3.0mg BID for subjects >50kg.

Participant Flow:   Overall Study
    Randomized Medication - Lithium     Randomized Medication - Divalproex Sodium     Randomized Medication - Risperidone  
STARTED     137     139     103  
COMPLETED     72     67     69  
NOT COMPLETED     65     72     34  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Randomized Medication - Lithium Participants will receive treatment with lithium for 8 to 16 weeks. At the initial dispensing visit, dose was 150mg qHS for 2 days, then 150mg BID for subjects <25kg; 150mg BID for 2 days, then 300mg BID for subjects 25-50kg; 300mg BID for 2 days, then 300mg AM / 600mg PM for subjects >50kg. Dose was adjusted to achieve blood levels of 0.8 mEq/L at week 1, 0.9-1.0 mEq/L at weeks 2-3, and 1.1-1.3 mEq/L at weeks 4-7.
Randomized Medication - Divalproex Sodium Participants will receive treatment with divalproex sodium for 8 to 16 weeks. At the initial dispensing visit, dose was 125mg qHS for 2 days, then 125mg BID for subjects <25kg; 250mg qHS for 2 days, then 125mg AM / 250mg PM for subjects 25-50kg; 250mg qHS for 2 days, then 250mg BID for subjects >50kg. Dose was adjusted to achieve blood levels of 75 ug/ml at week 1, 100-110 ug/ml at weeks 2-3, and 111-125 ug/ml at weeks 4-7.
Randomized Medication - Risperidone Participants will receive treatment with risperidone for 8 to 16 weeks. At the initial dispensing visit, dose was 0.25mg qHS for 2 days, then 0.25mg BID for subjects <25kg; 0.25mg BID for 2 days, then 0.5mg BID for subjects 25-50kg; 0.25mg BID for 2 days, then 0.5mg BID for subjects >50kg. Dose was adjusted at weeks 2-3 to 0.5mg BID for subjects <25kg, 1.0mg BID for subjects 25-50kg and >50kg. Dose was adjusted at weeks 4-5 to 1.0mg BID for subjects <25kg, 1.5mg BID for subjects 25-50kg, 2.0kg BID for subjects >50kg. Dose was adjusted at weeks 6-7 to 2.0mg BID for subjects <25kg, 2.0mg AM / 3.0mg PM for subjects 25-50kg, 3.0mg BID for subjects >50kg.
Total Total of all reporting groups

Baseline Measures
    Randomized Medication - Lithium     Randomized Medication - Divalproex Sodium     Randomized Medication - Risperidone     Total  
Number of Participants  
[units: participants]
  137     139     103     379  
Age  
[units: participants]
       
<=18 years     137     139     103     379  
Between 18 and 65 years     0     0     0     0  
>=65 years     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  9.92  ± 2.79     9.85  ± 2.37     10.99  ± 2.95     10.19  ± 2.73  
Gender  
[units: participants]
       
Female     53     70     52     175  
Male     84     69     51     204  
Region of Enrollment  
[units: participants]
       
United States     137     139     103     379  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Clinical Global Impressions-Bipolar Mania Improvement   [ Time Frame: Measured at Week 8 ]

2.  Secondary:   Modified Side Effects Form for Children and Adolescents   [ Time Frame: Measured at Week 8 ]

3.  Secondary:   K-SADS Mania Rating Scale   [ Time Frame: Measured at Week 8 ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
Randomized Medication - Lithium Participants will receive treatment with lithium for 8 to 16 weeks. At the initial dispensing visit, dose was 150mg qHS for 2 days, then 150mg BID for subjects <25kg; 150mg BID for 2 days, then 300mg BID for subjects 25-50kg; 300mg BID for 2 days, then 300mg AM / 600mg PM for subjects >50kg. Dose was adjusted to achieve blood levels of 0.8 mEq/L at week 1, 0.9-1.0 mEq/L at weeks 2-3, and 1.1-1.3 mEq/L at weeks 4-7.
Randomized Medication - Divalproex Sodium Participants will receive treatment with divalproex sodium for 8 to 16 weeks. At the initial dispensing visit, dose was 125mg qHS for 2 days, then 125mg BID for subjects <25kg; 250mg qHS for 2 days, then 125mg AM / 250mg PM for subjects 25-50kg; 250mg qHS for 2 days, then 250mg BID for subjects >50kg. Dose was adjusted to achieve blood levels of 75 ug/ml at week 1, 100-110 ug/ml at weeks 2-3, and 111-125 ug/ml at weeks 4-7.
Randomized Medication - Risperidone Participants will receive treatment with risperidone for 8 to 16 weeks. At the initial dispensing visit, dose was 0.25mg qHS for 2 days, then 0.25mg BID for subjects <25kg; 0.25mg BID for 2 days, then 0.5mg BID for subjects 25-50kg; 0.25mg BID for 2 days, then 0.5mg BID for subjects >50kg. Dose was adjusted at weeks 2-3 to 0.5mg BID for subjects <25kg, 1.0mg BID for subjects 25-50kg and >50kg. Dose was adjusted at weeks 4-5 to 1.0mg BID for subjects <25kg, 1.5mg BID for subjects 25-50kg, 2.0kg BID for subjects >50kg. Dose was adjusted at weeks 6-7 to 2.0mg BID for subjects <25kg, 2.0mg AM / 3.0mg PM for subjects 25-50kg, 3.0mg BID for subjects >50kg.

Serious Adverse Events
    Randomized Medication - Lithium     Randomized Medication - Divalproex Sodium     Randomized Medication - Risperidone  
Total, serious adverse events        
# participants affected / at risk     6/137 (4.38%)     4/139 (2.88%)     5/103 (4.85%)  
Psychiatric disorders        
Hospitalization † [2]      
# participants affected / at risk     5/137 (3.65%)     4/139 (2.88%)     5/103 (4.85%)  
# events     5     4     5  
Event requiring intervention to prevent permanent impairment or damage † [3]      
# participants affected / at risk     1/137 (0.73%)     0/139 (0.00%)     0/103 (0.00%)  
# events     1     0     0  
Events were collected by systematic assessment
[2] Admission to the hospital or prolongation of a hospital stay results because of the adverse event.
[3] A condition that requires medical or surgical intervention to preclude permanent impairment or damage to a subject.




  Other Adverse Events


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Barbara Geller, M.D.
Organization: Washington University in St. Louis
phone: 314-747-3657
e-mail: gellerb@wustl.edu


Publications of Results:
Other Publications:
Publications automatically indexed to this study:

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00057681     History of Changes
Other Study ID Numbers: U01 MH64846-06, U01MH064846, U01MH064911, U01MH064868, U01MH064887, U01MH064850, U01MH064869
Study First Received: April 4, 2003
Results First Received: May 29, 2012
Last Updated: March 27, 2013
Health Authority: United States: Federal Government