Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder
Pediatric Bipolar Disorder (BD) is uncommon in children. Its symptoms include periods of manic behavior (being overly happy or giddy, feeling grandiose, feeling a decreased need for sleep, having too much energy, moving more than usual, talking fast, having speeded-up thoughts and other symptoms). Sometimes there also is depression (extreme feelings of sadness or irritability, not taking pleasure in things, even ones that used to be enjoyable, feeling worthless or guilty, sleeping too much or having trouble getting to or staying asleep, feeling slowed down or restless, having wishes to be dead or suicidal ideas, and other symptoms). Pediatric BD is often difficult to treat; children may respond only partially to the medications now available or have too many side effects to tolerate them.
Riluzole is a medication that is thought to work on a brain chemical called glutamate that may be involved in symptoms of depression and BD. Previous research studies have shown that riluzole may help adults with BD who have depression and adults who have depression, anxiety disorders, or obsessive-compulsive disorders. Riluzole may also be helpful for children with obsessive-compulsive disorder. However, it has never been given to children with BD.
This study will evaluate the effectiveness of riluzole in 80 patients between 9 and 17 years of age who have BD and symptoms of anxiety. Participants must have tried at least two other medications that have not been effective.
The study will consist of four phases carried out over 4 to 5 months. Most children will be inpatients at the Pediatric Behavioral Health Unit for at least part of the study.
In Phase 1, each patient will undergo blood and urine tests, and will gradually taper off his or her medication. The duration of this phase depends on the medication that the patient was receiving before starting the study.
In Phase 2, the patient will remain off all medication for 1 week. Throughout this time, patients will be monitored carefully and medication will be restarted if needed.
In Phase 3, which lasts 8 weeks, patients will be assigned randomly to receive only riluzole or only a placebo. Those who receive riluzole will have the dose adjusted as needed. Patients and families will be informed of which drug they were on at the end of this phase. Patients who improved on riluzole may continue to receive it from NIH for 1 month and will then be prepared for discharge from the study. Patients who received placebo and improved, and those who received riluzole but did not improve, will be treated with standard medications as appropriate and prepared for discharge from the study.
Phase 4 is for patients who received placebo and did not improve. They will be given the chance to try riluzole for 8 weeks and, if it is effective, continue it for an additional 4 weeks while they prepare to be discharged from the study.
Patients will not be able to receive riluzole at the National Institutes of Health after the completion of the study. However, the child's doctor may be able to prescribe riluzole as an off-label use.
Most patients will be admitted to the Pediatric Behavioral Health Unit at the National Institutes of Health Clinical Center during the medication withdrawal part of the study (Phases 1 and 2). From Phase 3 on, a patient may participate as an inpatient, outpatient, or in day treatment, depending on what is in his or her best interests.
All participants in this study will be invited to also enroll in the National Institute of Mental Health protocol 00-M-0198, The Phenomenology and Neurophysiology of Affective Dysregulation In Children And Adolescents With Bipolar Disorder. Some research tests for that protocol will be done during the medication-free period of this protocol.
Bipolar Affective Disorder
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder|
- Clinical Global Impression--Improvement [ Time Frame: 8 week trial with the study running for about 4 years. ] [ Designated as safety issue: No ]This is a clinician rated measure that is a standard in pharmacological trials. the scores range from 1 to 8 with 5 being unchanged, 1 being completely recovered and 8 being markedly worse.
- Pediatric Anxiety Scale [ Time Frame: Weekly for 8 weeks ] [ Designated as safety issue: No ]A standard measure of severity of anxiety over the previous week. The score ranges from a total of 0-25, with 0 being absence of symptoms and impairment, and 25 being marked symptoms and severe impairment. The outcome measure for each participant is the change in PARS, that is, the difference at week 8 compared to baseline (when medication-free).
|Study Start Date:||November 2008|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
No Intervention: Medication Taper
All participants begin with gradual tapering to the point of discontinuing medication
Placebo Comparator: Random assignment to placebo
Once they are medication-free, 50% of participants are randomized to placebo
Active Comparator: Random assignment to riluzole
One they are medication-free, 50% of participants are randomized to riluzole
OBJECTIVE: To test the efficacy of riluzole in youth with bipolar disorder
STUDY POPULATION: Youth, ages 9-17, with DSM-IV bipolar disorder, who have failed to respond to two adequate trials of medication, one with an atypical antipsychotic medication, and the second with either a mood stabilizing medication or a second atypical antipsychotic medication.
DESIGN: Medication withdrawal, followed by a 15-day dose stabilization phase and a 6-week double-blind, placebo-controlled treatment trial. The first two phases will be completed as inpatients or in day treatment, while the third phase can be completed either in those settings or as an outpatient. Individuals who received placebo will be offered an 8-week open trial of riluzole followed by an additional 4 weeks if they respond, while those who received riluzole in the placebo-controlled trial and wish to continue it will receive 4 weeks of open treatment. Thus, all patients will have the opportunity to receive a total of 12 weeks of riluzole treatment.
OUTCOME MEASURES: Clinical rating scales, including the Pediatric Anxiety Rating Scale and the Clinical Global Improvement Scale
Please refer to this study by its ClinicalTrials.gov identifier: NCT00805493
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Ellen Leibenluft, MD||NIH, NIMH-IRP|