Bipolar DisorderPhase 3NCT00176202
Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar
A Phase 3 study testing Divalproex Sodium and risperidone in people with Bipolar Disorder, run by University of Illinois Chicago at 3 sites in United States.
Trial summary
The study is to examine the null hypothesis that risperidone and divalproex sodium are equally effective in treating/stabilizing pediatric bipolar disorder. Read more about this study
- Who is it for?
- Ages 10 to 20 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Divalproex Sodium and risperidone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2003to Jan 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children with Bipolar Disorder
- Must be able to swallow tablets
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Neuro Psychiatric Institute (NPI)
Chicago, Illinois, 60612
NPI, University of Illinois at Chicago
Chicago, Illinois, 60612
NPI
Chicago, Illinois, 60612
About this study
Official title: Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar
The study is to examine the null hypothesis that risperidone and divalproex sodium are equally effective in treating/stabilizing pediatric bipolar disorder.
Read the 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:
- Conditions
- Bipolar Disorder
- Being tested
- Divalproex Sodium, risperidone
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Divalproex SodiumDrug
Also called antiepileptic, valproic acid
Divalproex sodium is a mood stabilizer
risperidoneDrug
Also called antipsychotic, risperdal
Risperidone is a second generation antipsychotic and antimanic drug
| Study group | Role | What they receive |
|---|---|---|
| Risperidone | Active comparator | Risperidone is an antimanic medication and is a second generation antipsychotic Receives: Drug: risperidone |
| Divalproex sodium | Active comparator | Divalproex sodium is an antiepileptic medication and is a mood stabilizer Receives: Drug: Divalproex Sodium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startApr 2003
- Primary completionJan 2008
- Study completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mani Pavuluri, University of Illinois Chicago
- Investigators
- Mani Pavuluri, MD, Principal investigator, University of Ilinois at Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00176202
- Sponsor's protocol ID
- RIS-BIP-407
- Status last verified
- Nov 2015
- First submitted
- 9 Sep 2005
- Last updated
- 5 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pavuluri MN, Passarotti AM, Fitzgerald JM, Wegbreit E, Sweeney JA. Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):157-170.e5. doi: 10.1016/j.jaac.2011.10.019. Epub 2011 Dec 23.
PubMed 22265362
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Controlled Trial of Risperidone and Divalproex Sodium With MRI Assessment of Affected Circuitry in Pre and Post Treatment in Pediatric Bipolar
- ClinicalTrials.gov ID
- NCT00176202
- Acronym / sponsor ID
- RIS-BIP-407
- Conditions
- Bipolar Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Study start
- Apr 2003
- Primary completion
- Jan 2008 (actual)
- Study completion
- Jan 2008 (actual)
- First posted
- 15 Sep 2005 (estimated)
- Results
- Posted 5 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is to examine the null hypothesis that risperidone and divalproex sodium are equally effective in treating/stabilizing pediatric bipolar disorder.
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:
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Risperidone | Active comparator | Drug: risperidoneRisperidone is an antimanic medication and is a second generation antipsychotic |
| Divalproex sodium | Active comparator | Drug: Divalproex SodiumDivalproex sodium is an antiepileptic medication and is a mood stabilizer |
Who may qualify
- Ages
- 10 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Children with Bipolar Disorder
- Must be able to swallow tablets
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Divalproex SodiumAlso: antiepileptic, valproic acidDivalproex sodium is a mood stabilizer | Drug | Divalproex sodium |
| risperidoneAlso: antipsychotic, risperdalRisperidone is a second generation antipsychotic and antimanic drug | Drug | Risperidone |
Primary outcome
Young Mania Rating Scale (YMRS)
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).
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.
3 secondary outcomes
Child Depression Rating Scale- Revised (CDRS-R)
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)
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)
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22265362Pavuluri MN, Passarotti AM, Fitzgerald JM, Wegbreit E, Sweeney JA. Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging study. J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):157-170.e5. doi: 10.1016/j.jaac.2011.10.019. Epub 2011 Dec 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mani Pavuluri, MD principal investigator
University of Ilinois at Chicago
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Divalproex Sodium and risperidone in people with Bipolar Disorder, run by University of Illinois Chicago at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Young Mania Rating Scale (YMRS) (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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00176202, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2015.