Riluzole Augmentation Pilot in Depression (RAPID) Trial

Study Overview
=================
Brief Summary
-----------------
The investigators are doing a research study to find out if riluzole, when taken along with a standard antidepressant (sertraline) can help people with major depression. This research study will compare riluzole + sertraline to placebo + sertraline. The investigators hypothesize that adding riluzole will lead to a better antidepressant response, in less time, then sertraline alone.

Detailed Description
-----------------
Recent attention has focused on the glutamatergic system as a new, distinct target for depression treatment. Riluzole (Rilutek, Sanofi), an oral modulator of glutamate activity with neuroprotective and anticonvulsant properties, is currently approved by the United States Food and Drug Administration for treatment of amyotrophic lateral sclerosis (ALS). Preliminary studies using riluzole to treat depression in humans are promising, though larger, double-blinded controlled trials are needed. Overall study population: Adult outpatients with a current, untreated major depressive episode. Disallowed therapies include: other psychotropic medications, including antipsychotics, mood stabilizers, benzodiazepines, barbiturates, other sedative-hypnotics, chronic opiates, or additional antidepressants, psychotherapy, electroconvulsive therapy, vagal nerve stimulations therapy, transcranial magnetic stimulation therapy, or phototherapy.

Official Title
-----------------
Riluzole Augmentation Pilot in Depression (RAPID) Trial

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Drug: Riluzole
* Drug: Sertraline
* Other: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (ages 18-75) who meet DSM-IV criteria for a major depressive episode, Hamilton Depression Rating Scale (HDRS) >22, and No antidepressant treatment for at least three weeks Exclusion Criteria: Active drug or alcohol disorder in the past 3 months History of psychosis, history of mania or hypomania Epilepsy or history of seizures Hypothyroidism Congenital QTc prolongation Liver disease Lung disease Acute suicide or homicide risk Pregnant women, breastfeeding women, women of childbearing age not using contraception Unstable medical illness Elevated thyroid-stimulating hormone (TSH>5.0mlU/L), or Abnormal liver function tests (ALT>50 U/L or AST>50 U/L) ADD / ADHD (Attention deficit hyperactivity disorder) Disallowed therapies include: other psychotropic medications, including antipsychotics, mood stabilizers, benzodiazepines, barbiturates, other sedative-hypnotics, chronic opiates, or additional antidepressants, psychotherapy, electroconvulsive therapy, vagal nerve stimulations therapy, transcranial magnetic stimulation therapy, or phototherapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sertraline + riluzole<br>sertraline 100 mg po daily and riluzole 50 mg po bid | Drug: Riluzole<br> <br> * Other names: Rilutek;Drug: Sertraline<br> <br> * Other names: Zoloft;|
| Active Comparator: sertraline + placebo<br>sertraline 100 mg po daily and placebo | Drug: Sertraline<br> <br> * Other names: Zoloft;Other: placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52. | 0 weeks-8 weeks | 
| Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks | The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52. | 0 weeks-8 weeks | 
| Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks | The Hamilton Depression Rating Scale (HDRS) is a clinician-administered semi-structured interview with 17 questions. It is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. Higher HDRS scores indicate a worse outcome. The scale has a minimum value of 0 and a maximum value of 52. | 0 weeks-8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks | The HARS scale is a clinician rated interview scale designed to measure the signs and symptoms of anxiety. It has 14-items to rate the intensity of psychic and somatic anxiety on a 5-point severity scale. Each item ranging from 0 (not present) to 4 (very severe) were summed up to give a total possible score of 0 (not present) to 56 (very severe), where lower scores indicate less anxiety. | 0 weeks-8 weeks | 
| Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks | The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients). CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score. | 0 weeks-8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Major Depression, Major Depressive Disorder, Depression, Riluzole, Glutamate, Sertraline