Bipolar DisorderPhase 2NCT00805493
Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder
A Phase 2 study testing Riluzole in people with Bipolar Disorder and Anxiety Disorders, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 9 to 17 years
- Conditions the study is for
- Bipolar Disorder, Anxiety Disorders, Bipolar Affective Disorder
- What is being tested?
- Riluzole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Jun 2012
- Phase
- Phase 2
- 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 9 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Boys and girls
- Ages 9-17 years of age
- Meet DSM-IV criteria for bipolar disorder.
- The child must have a primary caregiver who can accompany him or her on trips to NIMH, provide reliable history and information, and complete rating scales.
- Patients must have a psychiatrist who provides clinical care for their BPD.
- All youth accepted into the study must be able to complete self-rating forms and to cooperate with other study procedures.
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- Previous treatment failure as defined by:
- Failure to respond to an adequate trial (adequate dose for at least two weeks) of a mood stabilizer (either lithium or divalproex) plus an adequate trial (sufficient dose for an adequate duration) of an atypical antipsychotic (such as risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole)
- Failure to respond to an adequate trial (sufficient dose for an adequate duration) of two atypical antipsychotics (such as risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole) or
- Evidence of intolerance (severe weight gain or other side effects) of a mood stabilizer or atypical antipsychotic agent.
- The child is failing his/her current treatment as defined by (all 3 met):
- The child's current CGAS score must be less than 60.
- The child's current psychiatrist must agree that the child's response to his/her current treatment is no more than minimal or there are drug side effects that are proving problematic. According to this criterion, it would be clinically appropriate to change the child's current treatment.
- On the basis of record review and interviews with child and parent, the research team agrees that the child's response to his/her current treatment is no more than minimal.
- Subject has a PARS score of greater than or equal to 10, derived from the total of the following individual items: 3 (overall severity of anxious feelings), 5 (overall avoidance), 6 (interference with family), and 7 (interference outside of the home). In addition, patients must score 3 or higher (i.e., in the clinical range) on at least one of the four items noted above.
Who cannot join
- I.Q. less than 70
- Autistic disorder or severe pervasive developmental disorder; psychosis that interferes with the child's capacity to understand and comply with study procedures;
- Unstable medical illness (e.g. severe asthma) or contraindication to riluzole
- Medical illness that could cause the symptoms of bipolar illness (e.g. multiple sclerosis, thyroid disease);
- Pregnancy
- Renal or hepatic dysfunction that would interfere with excretion or metabolism of riluzole as evidenced by increase above upper limits of normal for BUN/creatinine, or two-fold elevation of serum transaminases (ALT/SGPT, AST/SGOT), gamma glutamate (GGT), or bilirubin.
- Documented history of hypersensitivity or intolerance to riluzole.
- Substance abuse within two months of study entry
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
...
Read the detailed description
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
- Being tested
- Riluzole
- Keywords
- Mania, Bipolar, Bipolar Disorder, Bipolar Manic-Depressive Illness, Bipolar Mood Disorder
- Medical subject headings
- Bipolar Disorder, Anxiety Disorders, Mania
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RiluzoleDrug
| Study group | Role | What they receive |
|---|---|---|
| Medication Taper | No intervention | All participants begin with gradual tapering to the point of discontinuing medication |
| Random assignment to placebo | No intervention | Once they are medication-free, 50% of participants are randomized to placebo |
| Random assignment to riluzole | Active comparator | One they are medication-free, 50% of participants are randomized to riluzole Receives: Drug: Riluzole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Global Impression--Improvement
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.
Measured: 8 week trial with the study running for about 4 years.
Pediatric Anxiety Scale
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).
Measured: Weekly for 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionJun 2012
- Study completionJun 2012
Why it stopped: Insufficient recruitment of participants
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 (3)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 National Institute of Mental Health (NIMH)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ellen Leibenluft, MD, Principal investigator, NIH, NIMH-IRP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00805493
- Sponsor's protocol ID
- 090042
- Other IDs
- 09-M-0042
- Status last verified
- Sep 2017
- First submitted
- 6 Dec 2008
- Last updated
- 15 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Amiel JM, Mathew SJ. Glutamate and anxiety disorders. Curr Psychiatry Rep. 2007 Aug;9(4):278-83. doi: 10.1007/s11920-007-0033-7.
PubMed 17880858Axelson D, Birmaher B, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Bridge J, Keller M. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006 Oct;63(10):1139-48. doi: 10.1001/archpsyc.63.10.1139.
PubMed 17015816Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994 Mar 3;330(9):585-91. doi: 10.1056/NEJM199403033300901.
PubMed 8302340
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder
- ClinicalTrials.gov ID
- NCT00805493
- Acronym / sponsor ID
- 090042
- Keywords
- Mania, Bipolar, Bipolar Disorder, Bipolar Manic-Depressive Illness, Bipolar Mood Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient recruitment of participants
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- Nov 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 9 Dec 2008 (estimated)
- Results
- Posted 23 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Medication Taper | No intervention | –All participants begin with gradual tapering to the point of discontinuing medication |
| Random assignment to placebo | No intervention | –Once they are medication-free, 50% of participants are randomized to placebo |
| Random assignment to riluzole | Active comparator | Drug: RiluzoleOne they are medication-free, 50% of participants are randomized to riluzole |
Who may qualify
- Ages
- 9 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (15 listed)
- Boys and girls
- Ages 9-17 years of age
- Meet DSM-IV criteria for bipolar disorder.
- The child must have a primary caregiver who can accompany him or her on trips to NIMH, provide reliable history and information, and complete rating scales.
- Patients must have a psychiatrist who provides clinical care for their BPD.
Key exclusion criteria (8 listed)
- I.Q. less than 70
- Autistic disorder or severe pervasive developmental disorder; psychosis that interferes with the child's capacity to understand and comply with study procedures;
- Unstable medical illness (e.g. severe asthma) or contraindication to riluzole
- Medical illness that could cause the symptoms of bipolar illness (e.g. multiple sclerosis, thyroid disease);
- Pregnancy
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 |
|---|---|---|
| Riluzole | Drug | Random assignment to riluzole |
Primary outcome
Clinical Global Impression--Improvement
Time frame: 8 week trial with the study running for about 4 years.
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
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17880858Amiel JM, Mathew SJ. Glutamate and anxiety disorders. Curr Psychiatry Rep. 2007 Aug;9(4):278-83. doi: 10.1007/s11920-007-0033-7.
- Background: PubMed 17015816Axelson D, Birmaher B, Strober M, Gill MK, Valeri S, Chiappetta L, Ryan N, Leonard H, Hunt J, Iyengar S, Bridge J, Keller M. Phenomenology of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry. 2006 Oct;63(10):1139-48. doi: 10.1001/archpsyc.63.10.1139.
- Background: PubMed 8302340Bensimon G, Lacomblez L, Meininger V. A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994 Mar 3;330(9):585-91. doi: 10.1056/NEJM199403033300901.
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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.
Ellen Leibenluft, MD principal investigator
NIH, NIMH-IRP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riluzole in people with Bipolar Disorder and Anxiety Disorders, run by National Institute of Mental Health (NIMH) at 1 site 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 15 inclusion and 8 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: stopped early, as of the sponsor's last update on 15 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 23 Aug 2013). 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?
Clinical Global Impression--Improvement (time frame: 8 week trial with the study running for about 4 years.). The study lists 2 primary outcomes in all. 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 NCT00805493, which also lists 3 linked publications.
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 15 Sep 2017.