Riluzole to Treat Depression in Bipolar Disorder

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT00054704
First received: February 6, 2003
Last updated: March 14, 2014
Last verified: April 2013
  Purpose

This study examines if Riluzole, (FDA approved for ALS), will improve symptoms of depression in Bipolar Disorder.

Pupose: 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 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.


Condition Intervention Phase
Bipolar Disorder
Drug: Riluzole
Phase 2

Study Type: Interventional
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: An Investigation of the Antidepressant Efficacy of an Antiglutamatergic Agent in Bipolar Depression

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To evaluate the efficacy and safety of acute riluzole therapy in patients with bipolar I or II disorder current episode depressed without psychotic features according to the DSM-IV criteria, in improving overall depressive symptomology. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the efficacy and safety of acute riluzole therapy in patients with bipolar I or II disorder current episode depressed without psychotic features according to the DSM-IV criteria, in improving overall depressive symptomology. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 78
Study Start Date: February 2003
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Riluzole
    N/A
Detailed Description:

The treatments for acute unipolar depression have been extensively researched. However, despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of depressed patients fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Very few studies have examined the efficacy of somatic treatments for the acute phase of bipolar depression. Thus, there is a clear need to develop novel and improved therapeutics for bipolar depression. Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. Clinical data suggests that lamotrigine an inhibitor of glutamate release and the NMDA antagonist ketamine may have antidepressant effects. Finally, our group recently found in two separate studies that the glutamate modulating agent riluzole was effective in treatment-resistant unipolar and bipolar depression (Zarate et al 2004). Together, these data suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents, which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants.

In this study, we propose to extend our findings from open-label studies with riluzole in treatment-resistant depression by investigating its efficacy in a double-blind placebo-controlled study in bipolar depression.

Patients, ages 18 to 70 years with a diagnosis of bipolar disorder I or II current episode depressed (without psychotic features), will be randomized to double-blind treated to receive either riluzole (50-200 mg/day) or placebo for a period of 8 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.

Approximately 78 patients with acute bipolar depression will be enrolled in this study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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 DSM-IV based on clinical assessment and confirmed by structured diagnostic interview 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).

EXCLUSION CRITERIA:

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 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 CNS activity, other than specified in Appendix A.

Treatment with clozapine or 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00054704

Contacts
Contact: Libby Jolkovsky (877) 646-3644 libby_jolkovsky@nih.gov
Contact: Carlos A Zarate, M.D. (301) 451-0861 zaratec@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Carlos A Zarate, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier: NCT00054704     History of Changes
Other Study ID Numbers: 030092, 03-M-0092
Study First Received: February 6, 2003
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Riluzole
Neuroprotective
Open-Label Study
Glutamate Dysfunction
Bipolar Mood Disorder
Bipolar Disorder
Mood Disorder

Additional relevant MeSH terms:
Depression
Bipolar Disorder
Disease
Behavioral Symptoms
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Pathologic Processes
Riluzole
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on October 19, 2014