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

NCT00805493 | Terminated Phase 2 Results

• 2 other identifiers: 09004209-M-0042
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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). 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. ...

Conditions

Bipolar Disorder; Anxiety Disorders; Bipolar Affective Disorder; Bipolar Depression

Keywords

Mania; Bipolar; Bipolar Disorder; Bipolar Manic-Depressive Illness; Bipolar Mood Disorder

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  Weekly for 8 weeks

Study Arms (3)

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

Drug: Riluzole

Interventions

Riluzole DRUG

Random assignment to riluzole

Eligibility Criteria

• Age: 9 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Amiel JM, Mathew SJ. Glutamate and anxiety disorders. Curr Psychiatry Rep. 2007 Aug;9(4):278-83. doi: 10.1007/s11920-007-0033-7.

  PMID: 17880858 BACKGROUND

• 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. doi: 10.1001/archpsyc.63.10.1139.

  PMID: 17015816 BACKGROUND

• 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. doi: 10.1056/NEJM199403033300901.

  PMID: 8302340 BACKGROUND

MeSH Terms

Conditions

Bipolar Disorder; Anxiety Disorders; Mania

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Limitations in enrollment led to early termination of the study.

Results Point of Contact

• Title: Kenneth Towbin, M.D., Chief Clinical Child and Adolescent Psychiatry
• Organization: Emotion and Development Branch, NIMH-IRP

Kenneth.Towbin@nih.gov

301-402-4403

Study Officials

• Ellen Leibenluft, MD

  NIH, NIMH-IRP

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2008
• First Posted: December 9, 2008
• Study Start: November 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: September 15, 2017
• Results First Posted: August 23, 2013

Record last verified: 2017-09

Locations

US (1)