Riluzole Augmentation Pilot in Depression (RAPID) Trial

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01703039
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 2
• Actual Duration (Months): 65
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Riluzole; Drug: Sertraline; Other: placebo	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Riluzole Augmentation Pilot in Depression (RAPID) Trial
• Actual Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Jun 1, 2018
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

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	Drug: Sertraline; Other Names: Zoloft ; Other: placebo

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks [0 weeks-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.

2. Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks [0 weeks-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.

3. Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks [0 weeks-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.

Secondary Outcome Measures

1. Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks [0 weeks-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.

2. Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks [0 weeks-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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Jessica Harder, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 1, 2018

More Information

Publications

None provided.

• Responsible Party: Jessica Harder, Physician, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01703039
• Other Study ID Numbers: 2012P001841
• First Posted: Oct 10, 2012
• Last Update Posted: Aug 28, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Jessica Harder, Physician, Brigham and Women's Hospital: Major Depression; Major Depressive Disorder; Depression; Riluzole; Glutamate; Sertraline
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Riluzole; Sertraline

Study Results

Participant Flow

Arm/Group Title	Sertraline + Riluzole	Sertraline + Placebo
Arm/Group Description	sertraline 100 mg po daily and riluzole 50 mg po bid Riluzole Sertraline	sertraline 100 mg po daily and placebo Sertraline placebo
Period Title: Overall Study
STARTED	9	12
COMPLETED	6	7
NOT COMPLETED	3	5

Baseline Characteristics

Arm/Group Title	Sertraline + Riluzole	Sertraline + Placebo	Total
Arm/Group Description	sertraline 100 mg po daily and riluzole 50 mg po bid Riluzole Sertraline	sertraline 100 mg po daily and placebo Sertraline placebo	Total of all reporting groups
Overall Participants	6	7	13
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 83.3%	7 100%	12 92.3%
>=65 years	1 16.7%	0 0%	1 7.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.83 (14.88)	52.86 (7.71)	53.31 (11.06)
Sex: Female, Male (Count of Participants)
Female	3 50%	3 42.9%	6 46.2%
Male	3 50%	4 57.1%	7 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 14.3%	1 7.7%
Not Hispanic or Latino	4 66.7%	3 42.9%	7 53.8%
Unknown or Not Reported	2 33.3%	3 42.9%	5 38.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 14.3%	1 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 16.7%	1 14.3%	2 15.4%
White	4 66.7%	3 42.9%	7 53.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 16.7%	2 28.6%	3 23.1%
Region of Enrollment (Count of Participants)
United States	6 100%	7 100%	13 100%
Hamilton Depression Rating Scale (HDRS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26 (2.53)	25.14 (2.97)	25.54 (2.70)
Hamilton Anxiety Rating Scale (HARS) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	29.83 (7.33)	27.14 (10.12)	28.38 (8.69)
Clinical Global Impression Scale (CGI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5 (0.63)	5.14 (0.90)	5.08 (0.76)

Outcome Measures

1. Primary Outcome

Title	Mean Change in Hamilton Depression Rating Scale (HDRS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks
Description	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.
Time Frame	0 weeks-8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline + Riluzole	Sertraline + Placebo
Arm/Group Description	sert 100mg po daily and riluzole...	sert 100mg po daily and placebo...
Measure Participants	6	7
Mean (Standard Deviation) [score on a scale]	-5.67 (7.09)	-13.43 (6.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sertraline + Riluzole, Sertraline + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.06
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Number of Patients Experiencing an Antidepressant Response (>50% Reduction in HDRS) at Endpoint of 8 Weeks
Description	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.
Time Frame	0 weeks-8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline + Riluzole	Sertraline + Placebo
Arm/Group Description	sertraline 100 mg po daily and riluzole 50 mg po bid Riluzole Sertraline	sertraline 100 mg po daily and placebo Sertraline placebo
Measure Participants	6	7
Count of Participants [Participants]	1 16.7%	3 42.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sertraline + Riluzole, Sertraline + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Chi-squared
	Comments

3. Primary Outcome

Title	Number of Patients Experiencing Remission From Depression (HDRS<7) at Endpoint of 8 Weeks
Description	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.
Time Frame	0 weeks-8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline + Riluzole	Sertraline + Placebo
Arm/Group Description	sertraline 100 mg po daily and riluzole 50 mg po bid Riluzole Sertraline	sertraline 100 mg po daily and placebo Sertraline placebo
Measure Participants	6	7
Count of Participants [Participants]	0 0%	1 14.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sertraline + Riluzole, Sertraline + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Mean Change in Hamilton Anxiety Rating Scale (HARS) Score From Baseline (0 Weeks) to Endpoint at 8 Weeks
Description	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.
Time Frame	0 weeks-8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline + Riluzole	Sertraline + Placebo
Arm/Group Description	sertraline 100 mg po daily and riluzole 50 mg po bid Riluzole Sertraline	sertraline 100 mg po daily and placebo Sertraline placebo
Measure Participants	6	7
Mean (Standard Deviation) [score on a scale]	-9.50 (10.88)	-15.57 (7.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sertraline + Riluzole, Sertraline + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	ANOVA
	Comments

5. Secondary Outcome

Title	Mean Change in Clinical Global Impression (CGI) Scale From Baseline (0 Weeks) to Endpoint at 8 Weeks
Description	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.
Time Frame	0 weeks-8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sertraline + Riluzole	Sertraline + Placebo
Arm/Group Description	sertraline 100 mg po daily and riluzole 50 mg po bid Riluzole Sertraline	sertraline 100 mg po daily and placebo Sertraline placebo
Measure Participants	6	7
Mean (Standard Deviation) [score on a scale]	-0.67 (0.82)	-2.71 (1.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sertraline + Riluzole, Sertraline + Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Sertraline + Riluzole		Sertraline + Placebo
Arm/Group Description	sertraline 100 mg po daily and riluzole 50 mg po bid Riluzole Sertraline		sertraline 100 mg po daily and placebo Sertraline placebo
All Cause Mortality
	Sertraline + Riluzole		Sertraline + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/12 (0%)
Serious Adverse Events
	Sertraline + Riluzole		Sertraline + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Sertraline + Riluzole		Sertraline + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/9 (22.2%)		2/12 (16.7%)
Gastrointestinal disorders
Nausea	1/9 (11.1%)		0/12 (0%)
Elevated Liver Function Tests (LFTs)	1/9 (11.1%)		2/12 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.