Overview

This trial is active, not recruiting.

Condition depression
Treatments riluzole, placebo
Phase phase 2
Sponsor Yale University
Start date June 2011
End date May 2015
Trial size 150 participants
Trial identifier NCT01204918, HIC#0903004917, NCT01298427

Summary

This study aims to examine the antidepressant efficacy of riluzole, employing a randomized, double-blind, placebo-controlled, adjunctive trial in treatment-resistant major depressive disorder (TRD).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Riluzole 100mg added to ongoing SSRI or SNRI antidepressant
riluzole Rilutek
Riluzole 100mg PO for up to 8 weeks
(Placebo Comparator)
Placebo will be added to ongoing SSRI or SNRI antidepressant treatment
placebo
placebo

Primary Outcomes

Measure
Change in Montgomery and Asberg Depression Rating Scale (MADRS)
time frame: 8 weeks of therapy

Secondary Outcomes

Measure
Responders having at least a 50% improvement in MADRS compared to the baseline
time frame: 8 weeks therapy
Systematic Assessment for Treatment Emergent Events (SAFTEE-SI)
time frame: 8 weeks

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Group A inclusion/exclusion Inclusion Criteria: 1. Age 18-65 2. Written informed consent 3. Meets DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current 4. Inventory of Depressive Symptomatology - Self-Rated (IDS-SR30) score of > 20 at screening, baseline and start of double-blind phase (Phase 2) 5. May have a history of failure to respond to up to two FDA-approved antidepressants at adequate doses during the current episode for at least 8 weeks, and for inclusion into the Phase 2 subjects must have failed the 8-week prospective citalopram treatment. 6. Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of Phase 2. Exclusion Criteria: 1. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy) 2. Patients who no longer meet DSM-IV criteria for MDD during the baseline visit 3. Patients who demonstrate > 50% decrease in depressive symptoms as reflected by the IDS-SR total score from screen to baseline 4. Serious suicide or homicide risk, as assessed by evaluating clinician A serious suicide risk will be considered an inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death. 5. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease 6. The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past) 7. History of a seizure disorder or clinical evidence of untreated hypothyroidism 8. Patients requiring excluded medications (see Table 3 for details) 9. Psychotic features in the current episode or a history of psychotic features, as assessed by SCID 10. Any investigational psychotropic drug within the last 3 months 11. Have failed 3 or more adequate antidepressant trials during the current Major Depressive Episode by MGH-ATRQ criteria. 12. Patients with a history of antidepressant-induced hypomania. 13. Patients with any evidence of clinically significant liver abnormalities, or any liver transaminase level >1.5 X ULN at initial screening, or >5 x ULN during Phase 2 treatment. 14. Axis II personality disorders that are the primary purpose of treatment, or would interfere with a patient's safety or compliance. 15. Patients currently being treated for a respiratory disorder (including asthma or COPD) 16. Any subject who scores a 5 or higher on item #10 of the MADRS Group B inclusion/exclusion Inclusion criteria: 1. Age 18-65 2. Written informed consent 3. Meets DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current 4. Inventory of Depressive Symptomatology - Self-Rated (IDS-SR30) score of > 20 at screening and baseline visits, that is at the start of Phase 2 5. Has a history of failure to respond to 1, 2, or 3 FDA-approved antidepressants at adequate doses during the current episode for at least 8 weeks, as defined by the MGH Antidepressant Treatment Response Questionnaire (MGH-ATRQ), and must be currently on the failed SSRI for at least 8 weeks and on a stable dose for at least 4 weeks. 6. Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of Phase 2. Exclusion Criteria 1. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy) 2. Patients who no longer meet DSM-IV criteria for MDD during the baseline visit 3. Serious suicide or homicide risk, as assessed by evaluating clinician A serious suicide risk will be considered an inability to control suicide attempts, imminent risk of suicide in the investigator's judgment, or a history of serious suicidal behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS) as either (1) one or more actual suicide attempts in the 3 years before study entry with the lethality rated at 3 or higher, or (2) one or more interrupted suicide attempts with a potential lethality judged to result in serious injury or death. 4. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease 5. The following DSM-IV diagnoses: substance use disorders active within the last six months, any bipolar disorder (current or past), any psychotic disorder (current or past) 6. History of a seizure disorder or clinical evidence of untreated hypothyroidism; 7. Patients requiring excluded medications (see Table 3 for details) 8. Psychotic features in the current episode or a history of psychotic features, as assessed by SCID 9. Any investigational psychotropic drug within the last 3 months 10. Have failed 3 or more adequate antidepressant trials during the current Major Depressive Episode by MGH-ATRQ criteria. 11. Patients with a history of antidepressant-induced hypomania. 12. Patients with any evidence of clinically significant liver abnormalities, or any liver transaminase level >2 X ULN at initial screening, or >5 x ULN during Phase 2 treatment. 13. Axis II personality disorders that are the primary purpose of treatment, or would interfere with a patients safety or compliance. 14. Patients currently being treated for a respiratory disorder (including asthma or COPD) 15. Any subject who scores a 5 or higher on item #10 of the MADRS

Additional Information

Official title Efficacy and Tolerability of Riluzole in Treatment Resistant Depression
Principal investigator Gerard Sanacora, MD PhD
Description This study aims to examine the antidepressant efficacy of riluzole, employing a randomized, double-blind, placebo-controlled, 8 week trial of adjunctive trial in treatment-resistant major depressive disorder (TRD). Preclinical studies have shown riluzole to modulate Glu release and clearance, and to have potent neuroprotective properties, promoting neuro-resiliency. Other preclinical data now also show the drug to have antidepressant-like effects in rodent models used to screen for antidepressant activity. In addition, several small open-label clinical studies further suggest riluzole has antidepressant and anxiolytic properties, even in patients who do not respond to standard monoaminergic antidepressant and anxiolytic medications.
Trial information was received from ClinicalTrials.gov and was last updated in February 2015.
Information provided to ClinicalTrials.gov by Yale University.