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Efficacy and Tolerability of Riluzole in Treatment Resistant Depression

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ClinicalTrials.gov Identifier: NCT01204918
Recruitment Status : Completed
First Posted : September 17, 2010
Results First Posted : February 8, 2018
Last Update Posted : February 8, 2018
Sponsor:
Information provided by (Responsible Party):
Yale University

Brief 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).

Condition or disease Intervention/treatment Phase
Depression Drug: Riluzole Drug: placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 104 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Tolerability of Riluzole in Treatment Resistant Depression
Study Start Date : June 2011
Actual Primary Completion Date : May 2015
Actual Study Completion Date : August 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Riluzole
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Riluzole addition to SSRI antidepressant
Riluzole 100mg added to ongoing SSRI or SNRI antidepressant for 8 weeks
Drug: Riluzole
Riluzole 100mg PO
Other Name: Rilutek
Placebo Comparator: Placebo addition to standard SSRI antidepressant
Placebo will be added to ongoing SSRI or SNRI antidepressant treatment for 8 weeks
Drug: placebo
placebo
Experimental: Riluzole/Placebo addition to SSRI antidepressant
Riluzole 100mg added to ongoing SSRI or SNRI antidepressant for 4 weeks and placebo will added to ongoing SSRI or SNRI antidepressant treatment for 4 weeks
Drug: Riluzole
Riluzole 100mg PO
Other Name: Rilutek
Drug: placebo
placebo



Primary Outcome Measures :
  1. Change in Montgomery and Asberg Depression Rating Scale (MADRS) [ Time Frame: 4 weeks of therapy (baseline to week 4) ]

    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. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.

    Usual cutoff points are:

    0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression


  2. Change in Montgomery and Asberg Depression Rating Scale (MADRS) [ Time Frame: 4 weeks of therapy (week 4 to week 8) ]

    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. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.

    Usual cutoff points are:

    0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression



Secondary Outcome Measures :
  1. Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline [ Time Frame: 8 weeks therapy ]
    Responders having at least a 50% improvement in MADRS compared to the baseline in the sequential parallel design

  2. Systematic Assessment for Treatment Emergent Events (SAFTEE-SI) [ Time Frame: 8 weeks ]
    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. Presented below are counts of people that had experienced the event by 8 weeks.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01204918


Locations
United States, Connecticut
Yale University, Yale Depression Research Program
New Haven, Connecticut, United States, 06511
United States, Massachusetts
Massachussettes General Hospital, Depression Clinical and Research Center
Boston, Massachusetts, United States, 02114
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
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)

Publications:
Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT01204918     History of Changes
Obsolete Identifiers: NCT01298427
Other Study ID Numbers: HIC#0903004917
First Posted: September 17, 2010    Key Record Dates
Results First Posted: February 8, 2018
Last Update Posted: February 8, 2018
Last Verified: January 2018

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
Mood Disorders
Mental Disorders
Antidepressive Agents
Riluzole
Psychotropic Drugs
Anticonvulsants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents