Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Yale University
Sponsor:
Information provided by (Responsible Party):
Gerard Sanacora, Yale University
ClinicalTrials.gov Identifier:
NCT01204918
First received: September 16, 2010
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Depression
Drug: Riluzole
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Change in Montgomery and Asberg Depression Rating Scale (MADRS) [ Time Frame: 8 weeks of therapy ] [ Designated as safety issue: No ]
    This 10 item instrument is completed by the clinician by using a structured interview and defined anchor points, and aims to quantify the degree of depression over the past 7 days. The MADRS is a widely studied instrument for depression, and its reliability and validity are high. This instrument is administered at every study visit during the double-blind RCT, and at the screening, and baseline.


Secondary Outcome Measures:
  • Responders having at least a 50% improvement in MADRS compared to the baseline [ Time Frame: 8 weeks therapy ] [ Designated as safety issue: No ]
    Responders having at least a 50% improvement in MADRS compared to the baseline in the sequential parallel design

  • Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    a commonly used instrument originally developed by NIMH and adapted into a self-report instrument. The version of the scale that we plan to use examines in a systematic fashion all possible treatment-emergent side effects and probes specific adverse symptoms, including suicidal thoughts and behaviors, and self-injurious behavior.


Estimated Enrollment: 150
Study Start Date: June 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Riluzole addition to SSRI antidepressant
Riluzole 100mg added to ongoing SSRI or SNRI antidepressant
Drug: Riluzole
Riluzole 100mg PO for up to 8 weeks
Other Name: Rilutek
Placebo Comparator: Placebo addition to standard SSRI antidepressant
Placebo will be added to ongoing SSRI or SNRI antidepressant treatment
Drug: placebo
placebo

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01204918

Locations
United States, Connecticut
Yale University, Yale Depression Research Program Recruiting
New Haven, Connecticut, United States, 06519
Contact: Donna Fasula, APRN    203-764-9131    madonna.fasula@yale.edu   
Principal Investigator: Gerard Sanacora, MD PhD         
United States, Massachusetts
Massachussettes General Hospital, Depression Clinical and Research Center Recruiting
Boston, Massachusetts, United States, 02114
Contact: Amber Cardoos    617-724-9458    acardoos@mgh.harvard.edu   
Principal Investigator: Maurizo Fava, M.D.         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Alexandra Proctor    713-689-9856    aproctor@bcm.edu   
Contact: Kemp Knott    713-689-9856    kemp.knott@bcm.edu   
Principal Investigator: Sanjay Mathew, MD         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Gerard Sanacora, MD PhD Yale University
Principal Investigator: Maurizio Fava, MD Massachusettes General Hospital
Principal Investigator: Sanjay Matthew, MD Baylor College of Medicine
Principal Investigator: Carlos Zarate, MD National Institute of Mental Health (NIMH)
  More Information

Publications:
Responsible Party: Gerard Sanacora, Professor, Yale University
ClinicalTrials.gov Identifier: NCT01204918     History of Changes
Obsolete Identifiers: NCT01298427
Other Study ID Numbers: HIC#0903004917
Study First Received: September 16, 2010
Last Updated: January 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
MDD
Depression
Treatment refractory
Glutamate
Riluzole
Major depressive disorder
psychopharmacology
rilutek

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mental Disorders
Mood Disorders
Antidepressive Agents
Riluzole
Anticonvulsants
Central Nervous System Agents
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014