A Phase 3 interventional study of Divalproex Sodium and risperidone in Bipolar Disorder, sponsored by University of Illinois at Chicago. Completed at 3 sites in United States. Open to participants aged 10 Years to 20 Years. Per ClinicalTrials.gov, last updated 2015-11-05.
Sponsored by University of Illinois at Chicago · Phase 3, Interventional, and Treatment
The study is to examine the null hypothesis that risperidone and divalproex sodium are equally effective in treating/stabilizing pediatric bipolar disorder.
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:
1,601 studies on the registry are indexed under Bipolar Disorder; 254 are open to participants now.
This study's enrollment of 65 is close to the median of 64 across 1,223 interventional studies indexed under Bipolar Disorder.
Browse Bipolar Disorder studies →University of Illinois at Chicago is the lead sponsor of 515 studies on the registry; 133 are open to participants now.
Of its 31 completed or terminated interventional studies of FDA-regulated products, 18 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Risperidone is an antimanic medication and is a second generation antipsychotic
Drug: risperidone
Divalproex sodium is an antiepileptic medication and is a mood stabilizer
Drug: Divalproex Sodium
Divalproex sodium is a mood stabilizer
Also known as: antiepileptic, valproic acid
Risperidone is a second generation antipsychotic and antimanic drug
Also known as: antipsychotic, risperdal
Young Mania Rating Scale (YMRS)
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.
Time frame: 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 Depression Rating Scale- Revised (CDRS-R)
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.
Time frame: 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 (CMRS)
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.
Time frame: 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).
Clinical Global Improvement in Bipolar Disorder Overall (CGI-BP Overall)
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.
Time frame: 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).
Dates of recruitment :From Sep2005 - Jan 2008.in Clinic Subjects enrolled:65
| Milestone | Risperidone | Divalproex Sodium |
|---|---|---|
| Started | 32 | 33 |
| Completed | 27 | 17 |
| Not completed | 5 | 16 |
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.
| units on a scale | Divalproex | Risperidone |
|---|---|---|
| Baseline | 25.09 ± 7.51 | 30.59 ± 7.04 |
| Last observation carried forward (LOCF) | 15.24 ± 12.49 | 10.22 ± 10.50 |
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.
| units on a scale | Divalproex | Risperidone |
|---|---|---|
| Baseline | 40.76 ± 13.34 | 41.72 ± 17.44 |
| Last Observation Carried Forward (p<.01) | 35.76 ± 15.01 | 25.88 ± 9.13 |
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.
| units on scale | Risperidone | Divalproex Sodium |
|---|---|---|
| Baseline | 30.84 ± 10.87 | 28.0 ± 9.02 |
| LOCF | 16.35 ± 13.09 | 19.20 ± 12.66 |
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.
| units on a scale | Risperidone | Divalproex Sodium |
|---|---|---|
| Baseline | 4.80 ± 1.06 | 4.37 ± 0.67 |
| LOCF | 2.77 ± 1.28 | 2.97 ± 1.50 |
Collected over Weekly from baseline and for 6 weeks; 7 waves of data.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Risperidone | — | 0/32 (0%) | 8/32 (25%) |
| Depakote or Divalproex Sodium | — | 0/33 (0%) | 10/33 (30.3%) |
| Event | Risperidone | Depakote or Divalproex Sodium |
|---|---|---|
| Increased appetiteMetabolism and nutrition disorders | 8/32 | 10/33 |
| Irritable/agitatedNervous system disorders | 0/32 | 7/33 |
| stomach discomfortGastrointestinal disorders | 6/32 | 5/33 |
| sleepinessNervous system disorders | 5/32 | 4/33 |
| fatigue/tirednessNervous system disorders | 5/32 | 4/33 |
| insomniaNervous system disorders | 0/32 | 4/33 |
| weight gainMetabolism and nutrition disorders | 3/32 | 4/33 |
AGE 10 TO 20 YRS GENDER :BOTH
| Age, Continuous(years) | Risperidone | Divalproex | Total |
|---|---|---|---|
| Mean | 10.47 ± 3.18 | 11.23 ± 3.50 | 10.85 ± 3.34 |
| Sex: Female, Male(Participants) | Risperidone | Divalproex | Total |
|---|---|---|---|
| Female | 12 | 14 | 26 |
| Male | 20 | 19 | 39 |
| Region of Enrollment(participants) | Risperidone | Divalproex | Total |
|---|---|---|---|
| United States | 32 | 33 | 65 |
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University of Illinois at Chicago