Riluzole Augmentation Pilot in Depression (RAPID) Trial (RAPID)

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.

Study Overview

• Status: Terminated
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Other: placebo; Drug: Riluzole; Drug: Sertraline

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sertraline + riluzole; sertraline 100 mg po daily and riluzole 50 mg po bid	Drug: Riluzole; Other Names: Rilutek; Drug: Sertraline; Other Names: Zoloft
Active Comparator: sertraline + placebo; sertraline 100 mg po daily and placebo	Other: placebo; Drug: Sertraline; Other Names: Zoloft

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: October 4, 2012
• First Submitted That Met QC Criteria: October 5, 2012
• First Posted (Estimate): October 10, 2012

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 9, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Depression; Glutamate; Major Depressive Disorder; Major Depression; Riluzole; Sertraline
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neuroprotective Agents; Protective Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Anticonvulsants; Sertraline; Riluzole
• Other Study ID Numbers: 2012P001841

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No