Efficacy and Tolerability of Riluzole in Treatment Resistant Depression
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 3
- 主要终点
- Change in Montgomery and Asberg Depression Rating Scale (MADRS)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Meets DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current
- •Inventory of Depressive Symptomatology - Self-Rated (IDS-SR30) score of > 20 at screening, baseline and start of double-blind phase (Phase 2)
- •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.
- •Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of Phase 2.
排除标准
- •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)
- •Patients who no longer meet DSM-IV criteria for MDD during the baseline visit
- •Patients who demonstrate > 50% decrease in depressive symptoms as reflected by the IDS-SR total score from screen to baseline
- •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.
- •Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease
- •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)
- •History of a seizure disorder or clinical evidence of untreated hypothyroidism
- •Patients requiring excluded medications (see Table 3 for details)
- •Psychotic features in the current episode or a history of psychotic features, as assessed by SCID
- •Any investigational psychotropic drug within the last 3 months
- •Have failed 3 or more adequate antidepressant trials during the current Major Depressive Episode by MGH-ATRQ criteria.
- •Patients with a history of antidepressant-induced hypomania.
- •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.
- •Axis II personality disorders that are the primary purpose of treatment, or would interfere with a patient's safety or compliance.
- •Patients currently being treated for a respiratory disorder (including asthma or COPD)
- •Any subject who scores a 5 or higher on item #10 of the MADRS
- •Group B inclusion/exclusion
- •Inclusion criteria:
- •Written informed consent
- •Meets DSM-IV criteria (by Structured Clinical Interview for DSM-IV - SCID-I/P) for MDD, current
- •Inventory of Depressive Symptomatology - Self-Rated (IDS-SR30) score of > 20 at screening and baseline visits, that is at the start of Phase 2
- •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.
- •Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline and start of Phase
- •Exclusion Criteria
- •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)
- •Patients who no longer meet DSM-IV criteria for MDD during the baseline visit
- •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.
- •Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease
- •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)
- •History of a seizure disorder or clinical evidence of untreated hypothyroidism;
- •Patients requiring excluded medications (see Table 3 for details)
- •Psychotic features in the current episode or a history of psychotic features, as assessed by SCID
- •Any investigational psychotropic drug within the last 3 months
- •Have failed 3 or more adequate antidepressant trials during the current Major Depressive Episode by MGH-ATRQ criteria.
- •Patients with a history of antidepressant-induced hypomania.
- •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.
- •Axis II personality disorders that are the primary purpose of treatment, or would interfere with a patients safety or compliance.
- •Patients currently being treated for a respiratory disorder (including asthma or COPD)
- •Any subject who scores a 5 or higher on item #10 of the MADRS
研究组 & 干预措施
Riluzole addition to SSRI antidepressant
Riluzole 100mg added to ongoing SSRI or SNRI antidepressant for 8 weeks
干预措施: Riluzole (Drug)
Placebo addition to standard SSRI antidepressant
Placebo will be added to ongoing SSRI or SNRI antidepressant treatment for 8 weeks
干预措施: placebo (Drug)
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
干预措施: Riluzole (Drug)
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
干预措施: placebo (Drug)
结局指标
主要结局
Change in Montgomery and Asberg Depression Rating Scale (MADRS)
时间窗: 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
次要结局
- Responders Having at Least a 50% Improvement in MADRS Compared to the Baseline(8 weeks therapy)
- Systematic Assessment for Treatment Emergent Events (SAFTEE-SI)(8 weeks)