Trial Outcomes & Findings for Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar (NCT NCT00176202)
NCT ID: NCT00176202
Last Updated: 2015-11-05
Results Overview
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.
COMPLETED
PHASE3
65 participants
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).
2015-11-05
Participant Flow
Dates of recruitment :From Sep2005 - Jan 2008.in Clinic Subjects enrolled:65
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.
Participant milestones
| Measure |
Risperidone
The study aimed to compare the antipsychotic medication i.e., risperidone's efficacy with that of divalproex sodium (which is an antiepileptic medication) in treating/stabilizing pediatric bipolar disorder.
|
Divalproex Sodium
This is antiepileptic medication and is a comparator drug to see if it is as efficacious as risperidone assumption is both have equal efficacy with no difference between the two.
|
|---|---|---|
|
Overall Study
STARTED
|
32
|
33
|
|
Overall Study
COMPLETED
|
27
|
17
|
|
Overall Study
NOT COMPLETED
|
5
|
16
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar
Baseline characteristics by cohort
| Measure |
Risperidone
n=32 Participants
Risperidone is an antipsychotic medication and is used to treat mania. Its trade name is Risperdal.
Aim of the study is to cross compare the relative efficacy and safety of risperidone and divalproex sodium in treating/stabilizing mania in pediatric bipolar disorder.
|
Divalproex
n=33 Participants
Divalproex sodium, also referred to as divalproex is an antiepileptic medication used for mania and is referred to as mood stabilizer. Its trade name is Depakote.
|
Total
n=65 Participants
Total of all reporting groups
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|---|---|---|---|
|
Age, Continuous
|
10.47 years
STANDARD_DEVIATION 3.18 • n=5 Participants
|
11.23 years
STANDARD_DEVIATION 3.50 • n=7 Participants
|
10.85 years
STANDARD_DEVIATION 3.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
32 participants
n=5 Participants
|
33 participants
n=7 Participants
|
65 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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).Population: Inclusion criteria were a DSM-IV diagnosis of bipolar disorder Type I (mixed or manic episode); 8 to 18 years old; and medication free or currently clinically unstable on medication, justifying termination of the ineffective regimen.
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.
Outcome measures
| Measure |
Divalproex
n=33 Participants
Divalproex was titrated up to 15 mg/kg/day over 3 days and serum level was measured at the end of 5 days. Divalproex dose was immediately adjusted on obtaining the serum level to aim for 80-120 μg/ml- trough, while ensuring that the dose was tolerated when increased. Serum valproate level was repeated at the end of the study.
|
Risperidone
n=32 Participants
Risperidone was initiated at 0.25 mg to 0.50 mg per day. The dose was titrated to a maximum of 2 mg per day by increments of 0.25-0.5 mg every 2 days to achieve a maximum tolerable level by day 7.
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|---|---|---|
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Young Mania Rating Scale (YMRS)
Baseline
|
25.09 units on a scale
Standard Deviation 7.51
|
30.59 units on a scale
Standard Deviation 7.04
|
|
Young Mania Rating Scale (YMRS)
Last observation carried forward (LOCF)
|
15.24 units on a scale
Standard Deviation 12.49
|
10.22 units on a scale
Standard Deviation 10.50
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Divalproex
n=33 Participants
Divalproex was titrated up to 15 mg/kg/day over 3 days and serum level was measured at the end of 5 days. Divalproex dose was immediately adjusted on obtaining the serum level to aim for 80-120 μg/ml- trough, while ensuring that the dose was tolerated when increased. Serum valproate level was repeated at the end of the study.
|
Risperidone
n=32 Participants
Risperidone was initiated at 0.25 mg to 0.50 mg per day. The dose was titrated to a maximum of 2 mg per day by increments of 0.25-0.5 mg every 2 days to achieve a maximum tolerable level by day 7.
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|---|---|---|
|
Child Depression Rating Scale- Revised (CDRS-R)
Last Observation Carried Forward (p<.01)
|
35.76 units on a scale
Standard Deviation 15.01
|
25.88 units on a scale
Standard Deviation 9.13
|
|
Child Depression Rating Scale- Revised (CDRS-R)
Baseline
|
40.76 units on a scale
Standard Deviation 13.34
|
41.72 units on a scale
Standard Deviation 17.44
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Divalproex
n=32 Participants
Divalproex was titrated up to 15 mg/kg/day over 3 days and serum level was measured at the end of 5 days. Divalproex dose was immediately adjusted on obtaining the serum level to aim for 80-120 μg/ml- trough, while ensuring that the dose was tolerated when increased. Serum valproate level was repeated at the end of the study.
|
Risperidone
n=33 Participants
Risperidone was initiated at 0.25 mg to 0.50 mg per day. The dose was titrated to a maximum of 2 mg per day by increments of 0.25-0.5 mg every 2 days to achieve a maximum tolerable level by day 7.
|
|---|---|---|
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Child Mania Rating Scale (CMRS)
Baseline
|
30.84 units on scale
Standard Deviation 10.87
|
28.0 units on scale
Standard Deviation 9.02
|
|
Child Mania Rating Scale (CMRS)
LOCF
|
16.35 units on scale
Standard Deviation 13.09
|
19.20 units on scale
Standard Deviation 12.66
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Divalproex
n=32 Participants
Divalproex was titrated up to 15 mg/kg/day over 3 days and serum level was measured at the end of 5 days. Divalproex dose was immediately adjusted on obtaining the serum level to aim for 80-120 μg/ml- trough, while ensuring that the dose was tolerated when increased. Serum valproate level was repeated at the end of the study.
|
Risperidone
n=33 Participants
Risperidone was initiated at 0.25 mg to 0.50 mg per day. The dose was titrated to a maximum of 2 mg per day by increments of 0.25-0.5 mg every 2 days to achieve a maximum tolerable level by day 7.
|
|---|---|---|
|
Clinical Global Improvement in Bipolar Disorder Overall (CGI-BP Overall)
Baseline
|
4.80 units on a scale
Standard Deviation 1.06
|
4.37 units on a scale
Standard Deviation 0.67
|
|
Clinical Global Improvement in Bipolar Disorder Overall (CGI-BP Overall)
LOCF
|
2.77 units on a scale
Standard Deviation 1.28
|
2.97 units on a scale
Standard Deviation 1.50
|
Adverse Events
Risperidone
Depakote or Divalproex Sodium
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Risperidone
n=32 participants at risk
Likely side effects include weight gain, muscle stiffness, sedation and tiredness.
Clarification: We did not note any serious side effects with either drug. We reported any adverse event that is found in greater than 5% of the participants in each group. Frequency of adverse events do not equal the fact that they are serious adverse events at any individual level.
|
Depakote or Divalproex Sodium
n=33 participants at risk
Likely side effects include gastrointestinal side effects such as stomach discomfort, weight gain, agitation and sedation, fatigue or tiredness.
Clarification: We did not note any serious side effects with either drug. We reported any adverse event that is found in greater than 5% of the participants in each group. Frequency of adverse events do not equal the fact that they are serious adverse events at any individual level.
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|---|---|---|
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Metabolism and nutrition disorders
Increased appetite
|
25.0%
8/32 • Number of events 8 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
30.3%
10/33 • Number of events 10 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
|
Nervous system disorders
Irritable/agitated
|
0.00%
0/32 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
21.2%
7/33 • Number of events 7 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
|
Gastrointestinal disorders
stomach discomfort
|
18.8%
6/32 • Number of events 6 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
15.2%
5/33 • Number of events 5 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
|
Nervous system disorders
sleepiness
|
15.6%
5/32 • Number of events 5 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
12.1%
4/33 • Number of events 4 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
|
Nervous system disorders
fatigue/tiredness
|
15.6%
5/32 • Number of events 5 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
12.1%
4/33 • Number of events 4 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
|
Nervous system disorders
insomnia
|
0.00%
0/32 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
12.1%
4/33 • Number of events 4 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
|
Metabolism and nutrition disorders
weight gain
|
9.4%
3/32 • Number of events 3 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
12.1%
4/33 • Number of events 4 • Weekly from baseline and for 6 weeks; 7 waves of data.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place