Riluzole to Treat Depression in Bipolar Disorder

NCT00054704 | Terminated Phase 2 Results DMC

• 2 other identifiers: 03009203-M-0092
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study examines if Riluzole, FDA approved for ALS, will improve symptoms of depression in Bipolar Disorder. Purpose: This study will examine the safety and effectiveness of riluzole (Rilutek trademark) for short-term treatment of depression symptoms, such as depressed mood, psychomotor retardation, and excessive sleeping in patients with bipolar disease. Riluzole is approved by the Food and Drug Administration (FDA) to treat amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). Preliminary findings of a study using riluzole to treat acute depression in patients with unipolar depression indicate that it may have antidepressant properties in some patients. Patients between 18 and 70 years of age with bipolar I or II disorder without psychosis may be eligible for this 8-week study. Candidates must be currently depressed, must have had at least one previous major depressive episode, and must have failed to improve with prior treatment with at least one antidepressant. They will be screened with a medical history, physical examination, electrocardiogram (EKG), blood and urine tests, and psychiatric evaluation. A blood or urine sample will be analyzed for illegal drugs. Women of childbearing potential will have a pregnancy test. Participants will begin an 8-week course of treatment, starting with a placebo (a sugar pill formulated to look like the active drug) and, at some point, switching to riluzole. In addition to drug treatment, participants will undergo the following procedures: Physical examination and electrocardiogram (EKG) at the beginning and end of the study; Weekly check of vital signs (temperature, blood pressure and heart rate); Weekly 1-hour interviews consisting of psychiatric and psychomotor rating scales to assess treatment response; Weekly blood tests to measure blood levels of riluzole and evaluate drug side effects. At the end of the study, participants' psychiatric status will be reassessed and appropriate long-term psychiatric treatment arranged. Atendemos pacientes de habla hispana. We enroll eligible participants locally and from around the country. Travel arrangements are provided and costs covered by the National Institute of Mental Health (NIMH). (Arrangements vary by distance and by specific study.) After completing the study participants receive short-term follow-up care while transitioning back to a provider.

Conditions

Bipolar Disorder

Keywords

Riluzole; Neuroprotective; Open-Label Study; Glutamate Dysfunction; Bipolar Mood Disorder; Bipolar Disorder; Mood Disorder

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale

  The Montgomery-Asberg Depression Rating Scale (MADRS) is a clinician-rated assessment of depression symptoms. Patients were rated weekly on 10 symptoms on a scale of 0 to 6 for each item, where 0 indicated no symptoms and 6 indicated the highest severity of that symptom. Total scores range from 0 to 60, where a moderate severity of depression would be present with a score of at least 20.

  8 weeks

Study Arms (2)

Riluzole

EXPERIMENTAL

Riluzole was dispensed either once or twice a day as 50 mg tablets. Riluzole dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.

Drug: Riluzole

Placebo

PLACEBO COMPARATOR

Placebo pills resembling 50 mg riluzole tables were dispensed either once or twice a day. Dosing began at 50 mg twice per day by mouth and was increased on a weekly basis by 50 mg, as tolerated, to achieve a dose of 200 mg/day. Dose escalations continued until at least a 50% reduction in depression (MADRS) scores, intolerable side effects, or study completion. Dose was raised on a weekly basis by 50 mg until the dose of 200 mg was achieved unless precluded by an adverse event. If significant side effects occurred, titration was slowed and doses were reduced under double-blind conditions. The maximum permitted dose of riluzole was 200 mg/day. Those subjects not tolerating a dosage of 50 mg/day were removed from the study.

Drug: Placebo

Interventions

Riluzole DRUG

Riluzole

Also known as: Rilutek

Riluzole

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, 18-70 years of age.
• Female subjects of childbearing potential must be using a medically accepted means of contraception.
• Each subject must have a level of understanding sufficient to agree to all required tests and examinations.
• Each subject must understand the nature of the study and must sign an informed consent document.
• Subjects must fulfill the criteria bipolar I or II disorder, current episode depressed without psychotic features as defined in the Diagnostic and Statistical Manual (DSM-IV) based on clinical assessment and confirmed by the Structured Clinical Interview for DSM (SCID-P).
• Subjects must have an initial score at Visit 1 and Visit 2 of at least 20 on the MADRS.
• Current duration of depressive episode should be at least 4 weeks.
• Subjects must have experienced, in the opinion of the investigator, at least one previous major depressive episode as defined in DSM-IV (not including the current major depressive episode).

You may not qualify if:

• Presence of psychotic features.
• Female subjects who are either pregnant or nursing.
• Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
• Subjects with uncorrected hypothyroidism or hyperthyroidism.
• Clinically significant abnormal laboratory tests.
• Current or past blood dyscrasia.
• Documented history of hypersensitivity or intolerance to riluzole.
• DSM-IV substance abuse or dependence within the past 90 days. No alcohol or recreational drug use will be permitted during the study.
• Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to visit 2.
• Treatment with a reversible monoamine oxidase inhibitor (MAOI), guanethidine, or guanadrel within 1 week or with fluoxetine within 5 weeks prior to Visit 2.
• Treatment with any other concomitant medication with primarily central nervous system (CNS) activity, other than specified in Appendix A.
• Treatment with clozapine or electroconvulsive therapy (ECT) within 4 weeks prior to Visit 2.
• Current diagnosis of schizophrenia or other psychotic disorder as defined in the DSM-IV.
• Current Axis I Anxiety Disorder that is clinically significant.
• Judged clinically to be at serious suicidal risk.

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 (5)

• Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993 Nov;150(11):1731-3. doi: 10.1176/ajp.150.11.1731.

  PMID: 8214185 BACKGROUND

• Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000 Feb 15;47(4):305-13. doi: 10.1016/s0006-3223(99)00159-6.

  PMID: 10686265 BACKGROUND

• Bae HJ, Lee YS, Kang DW, Koo JS, Yoon BW, Roh JK. Neuroprotective effect of low dose riluzole in gerbil model of transient global ischemia. Neurosci Lett. 2000 Nov 10;294(1):29-32. doi: 10.1016/s0304-3940(00)01536-6.

  PMID: 11044579 BACKGROUND

• Hejazi NS, Farmer CA, Oppenheimer M, Falodun TB, Park LT, Duncan WC Jr, Zarate CA Jr. The relationship between the HDRS insomnia items and polysomnographic (PSG) measures in individuals with treatment-resistant depression. J Psychiatr Res. 2022 Apr;148:27-33. doi: 10.1016/j.jpsychires.2022.01.022. Epub 2022 Jan 11.

  PMID: 35092868 DERIVED

• Park LT, Lener MS, Hopkins M, Iadorola N, Machado-Vieira R, Ballard E, Nugent A, Zarate CA Jr. A Double-Blind, Placebo-Controlled, Pilot Study of Riluzole Monotherapy for Acute Bipolar Depression. J Clin Psychopharmacol. 2017 Jun;37(3):355-358. doi: 10.1097/JCP.0000000000000693.

  PMID: 28338546 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Mood Disorders

Interventions

Riluzole

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mental Disorders

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

The study was terminated due to results suggesting the active drug was leading to worse outcomes than placebo.

Results Point of Contact

• Title: Dr. Carlos Zarate
• Organization: NIMH, DIRP, Experimental Therapeutics and Pathophysiology Branch

zaratec@mail.nih.gov

3014510861

Study Officials

• Carlos A Zarate, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: February 6, 2003
• First Posted: February 7, 2003
• Study Start: February 1, 2003
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: April 25, 2019
• Results First Posted: May 2, 2016

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)