Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder - Full Text View

Sponsor:	National Institute of Mental Health (NIMH)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00805493

Purpose

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 rec...

Condition	Intervention	Phase
Bipolar Disorder Anxiety Disorders Bipolar Affective Disorder Bipolar Depression	Drug: Riluzole	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Double-Blind Placebo-Controlled Trial of Riluzole in Pediatric Bipolar Disorder

Resource links provided by NLM:

MedlinePlus related topics: Anxiety Bipolar Disorder Depression

Drug Information available for: Riluzole

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Pediatric Anxiety Rating Scale; Clinical Global Impression--Improvement [ Time Frame: 8 week trial with the study running for about 4 years. ] [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	November 2008
Estimated Study Completion Date:	October 2012
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

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

Eligibility

Ages Eligible for Study:	9 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:
Boys and girls
Ages 9-17 years of age; 17 year-old participants who reach their 18th birthday while in the study will be allowed to continue and complete research and clinical care procedures under this protocol.
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.
Previous treatment failure as defined by:
1. 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) or
2. 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
3. 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):
1. The child's current CGAS score must be less than 60.
2. 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.
3. 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.

EXCLUSION CRITERIA:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805493

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Mental Health (NIMH)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Amiel JM, Mathew SJ. Glutamate and anxiety disorders. Curr Psychiatry Rep. 2007 Aug;9(4):278-83. Review.

Axelson 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.

Bensimon 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.

Responsible Party:	National Institutes of Health ( Ellen Leibenluft, M.D./National Institute of Mental Health )
Study ID Numbers:	090042, 09-M-0042
Study First Received:	December 6, 2008
Last Updated:	October 8, 2009
ClinicalTrials.gov Identifier:	NCT00805493 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Mania
Bipolar
Bipolar Disorder
Bipolar Manic-Depressive Illness

Bipolar Mood Disorder
Bipolar Disorder
Bipolar Mood Disorder
Bipolar Manic-Depressive Illness

Additional relevant MeSH terms:

Riluzole
Neurotransmitter Agents
Depression
Disease
Molecular Mechanisms of Pharmacological Action
Bipolar Disorder
Physiological Effects of Drugs
Excitatory Amino Acid Agents
Depressive Disorder
Protective Agents
Neuroprotective Agents

Pharmacologic Actions
Behavioral Symptoms
Affective Disorders, Psychotic
Pathologic Processes
Anxiety Disorders
Mental Disorders
Therapeutic Uses
Mood Disorders
Central Nervous System Agents
Anticonvulsants
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on November 05, 2009