Back to resultsNuedexta in Treatment-Resistant Major Depression
Primary Purpose
Major Depressive Disorder, Treatment Resistant
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
dextromethorphan/quinidine
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder focused on measuring depression, major depressive disorder, treatment resistant, Nuedexta, dextromethorphan, antidepressant, glutamate, NMDA receptor
Eligibility Criteria
Inclusion Criteria:
- Male or female participants, 18-65 years of age;
- Current primary Axis I diagnosis of major depressive disorder according to DSM-IV-TR criteria as determined by a psychiatrist and confirmed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID);
- Current treatment-resistant depression defined by a history of inadequate response to a minimum of 2 adequate antidepressant treatment trials determined by patient history and chart review and confirmed with the Antidepressant Treatment History Form (ATHF);
- Participants must be willing to discontinue treatment with concomitant medications that are disallowed by the study protocol;
- Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
Exclusion Criteria:
- Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorders or mental retardation
- Diagnosis of a substance use disorder within the past 1 year ;
- Female participants who are pregnant, nursing, for may become pregnant;
- Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- Participants with clinically significant abnormalities of laboratories, physical examination, or ECG;
- Prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, or heart failure;
- Complete atrioventricular (AV) block without implanted pacemaker, or patients at high risk of complete AV block
- Participants with a history of quinidine, quinine or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions;
- Participants judged to be at serious suicidal risk by the PI;
- Concomitant use with quinidine, quinine, or mefloquine;
- Participants with known hypersensitivity to dextromethorphan;
- Use with an MAOI or within 14 days of stopping an MAOI;
- Concomitant use with drugs that prolong QT interval and are metabolized by CYP2D6
Sites / Locations
- Icahn School of Medicine at Mount Sinai
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nuedexta (dextromethorphan/quinidine)
Arm Description
45/10 mg every 12 hours x 8 weeks
Outcomes
Primary Outcome Measures
Montgomery-Asberg Depression Rating Scale
The Montgomery-Asberg Depression Rating Scale is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is s scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). Primary outcome is change in MADRS at Visit 6 (Week 10). Higher values represent a worse outcome.
Secondary Outcome Measures
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form
The Quality of Life Enjoyment and Satisfaction Questionnaire Short Form is a reliable and valid self-report measure designed to obtain sensitive measures of the degree of enjoyment and satisfaction experienced by individuals. The raw total score ranges from 14 to 70. Higher scores reflect better oucomes.
Range of Impaired Functioning Tool
The Range of Impaired Functioning Tool a brief scale for assessing functional impairment related to medical or psychiatric illness and has been demonstrated to possess good psychometric properties. The LIFE-RIFT has a total score and individual domain scores for the following areas of functioning: household duties, work, recreation, relationships with family, relationships with friends, schoolwork, and global life satisfaction (the satisfaction item is patient rated).
Higher scores indicate poorer functioning; scores ≥2 reflect impaired functioning in that domain. Results are reported for the total sum with full range from 3 (no impairment) to 60 (severe impairment), which is based on all individual domain scores.
Sheehan Disability Scale
The Sheehan Disability Scale (SDS) is a self-rated scale which assesses illness-related disability in three areas of functioning: work, social and family. The SDS assess disability or functional impairment across three domains: work/school, social life/leisure activities and family life/home responsibilities. Each domain is scored from 0 (not at all) to 10 (very severely). The three domains can be summarized to evaluate global functional impairment by adding the scores of each of the three domains, resulting in global SDS score ranges from 0 (unimpaired) to 30 (highly impaired).
Patient Rated Inventory of Side Effects (PRISE)
Frequency of observed adverse events over the study treatment period as captured by the PRISE. The Patient Rated Inventory of Side Effects (PRISE) assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other).
Columbia-Suicide Severity Rating Scale (C-SSRS)
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a comprehensive, semi-structured interview measure that uniquely measures the full spectrum of suicidality including passive and active suicidal ideation, suicidal intent as well as suicidal behaviors. Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).
Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR)
The Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR) is a 16-item self rated instrument designed to assess the severity of depressive symptoms (30). The 16 items cover the nine symptom domains of major depression, and are rated on a scale of 0-3. Total score ranges from 0 to 27, with ranges of 0-5 (normal), 6-10 (mild), 11-15 (moderate), 16-20 (moderate to severe), and 21+ (severe).
Clinical Global Impression (CGI) Scale
The Clinical Global Impression (CGI) scale assesses overall treatment response in psychiatric patients and has good reliability and validity metrics. The administration time is 2 minutes. This scale consists of three items: Severity of Illness (item 1); Global Improvement (item 2); and Efficacy Index (item 3). Item 1 is rated on a seven-point scale (1 = normal, 7 = among the most extremely ill patients) as is item 2 (1 = very much improved, 7 = very much worse). Full scale is 1 to 14.
Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a brief scale to measure cognitive and executive dysfunction in mood and anxiety disorders, and possesses good reliability and validity. The Massachusetts General Hospital CPFQ was developed to assess each of the 7 most common complaints of depressed patients reporting fatigue or cognitive/executive problems. The CPFQ consists of 7 questions, each rated on a scale from 1 to 6, with 1 indicating greater than normal functioning, 2 indicating normal functioning and with higher numbers indicating poorer functioning. Total score range from 7 (greater than normal function) to 42 (poor function).
HAM-A
Change in Hamilton Anxiety Rating Scale (HAM-A) score from baseline to Week 10. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and >25-30 moderate to severe.
Beck Scale for Suicidal Ideation (BSI)
Mean change in Brief Inventory Symptom from baseline to week 10. The BSS is a self-report 19-item scale preceded by five screening items. The BSS and its screening items are intended to assess a patient's thoughts, plans and intent to commit suicide. All 24 items are rated on a three-point scale (0 to 2). In this study, scores from the five screening items were included in the overall score. Therefore, total scores could range from 0 to 48, with higher scores reflecting more severe symptoms.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01882829
Brief Title
Nuedexta in Treatment-Resistant Major Depression
Official Title
Targeting the NMDA Glutamate Receptor as Novel Antidepressant Strategy: A Pilot Clinical Trial of Nuedexta in Treatment-Resistant Major Depression
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
James Murrough
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
There is an urgent need, therefore, to identify well-tolerated, orally available compounds that target the NMDA receptor as a novel treatment approach for TRD. The current project aims to test the safety, tolerability and efficacy of Nuedexta - containing the NMDA antagonist dextromethorphan.
Detailed Description
Approximately one-third of patients with major depressive disorder do not achieve adequate symptom control despite a series of multiple treatment trials with currently available antidepressant medication (for example a serotonin-selective reuptake inhibitor). This group of patients - representing treatment-resistant depression (TRD) - accounts for an alarmingly high public health burden and signifies a critical area of need in pharmaceutical treatment development. While current treatments are slow to act and only partially effective, new basic and clinical research focusing on the glutamate system is yielding promising new avenues for novel drug discovery. Ketamine - a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist - has now been demonstrated in several studies to bring about a rapid and robust antidepressant effect, even in patients suffering from TRD. Ketamine is limited as a treatment for TRD by the need for intravenous administration and the potential for untoward medical or psychiatric adverse effects. There is an urgent need, therefore, to identify well-tolerated, orally available compounds that target the NMDA receptor as a novel treatment approach for TRD. The current project aims to test the safety, tolerability and efficacy of Nuedexta - containing the NMDA antagonist dextromethorphan.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Treatment Resistant
Keywords
depression, major depressive disorder, treatment resistant, Nuedexta, dextromethorphan, antidepressant, glutamate, NMDA receptor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Nuedexta (dextromethorphan/quinidine)
Arm Type
Experimental
Arm Description
45/10 mg every 12 hours x 8 weeks
Intervention Type
Drug
Intervention Name(s)
dextromethorphan/quinidine
Other Intervention Name(s)
Nuedexta
Intervention Description
up to 45/10 mg every 12 hours in patients with TRD with a short 7 day tapering period in which subjects are tapered off 45/10 mg dose from twice a day to once daily for an additional 7 days at post 8-week treatment period to minimize the potential for discontinuation effects
Primary Outcome Measure Information:
Title
Montgomery-Asberg Depression Rating Scale
Description
The Montgomery-Asberg Depression Rating Scale is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is s scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). Primary outcome is change in MADRS at Visit 6 (Week 10). Higher values represent a worse outcome.
Time Frame
At baseline and visit 6 (week 10)
Secondary Outcome Measure Information:
Title
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form
Description
The Quality of Life Enjoyment and Satisfaction Questionnaire Short Form is a reliable and valid self-report measure designed to obtain sensitive measures of the degree of enjoyment and satisfaction experienced by individuals. The raw total score ranges from 14 to 70. Higher scores reflect better oucomes.
Time Frame
At baseline and Visit 6 (week 10)
Title
Range of Impaired Functioning Tool
Description
The Range of Impaired Functioning Tool a brief scale for assessing functional impairment related to medical or psychiatric illness and has been demonstrated to possess good psychometric properties. The LIFE-RIFT has a total score and individual domain scores for the following areas of functioning: household duties, work, recreation, relationships with family, relationships with friends, schoolwork, and global life satisfaction (the satisfaction item is patient rated).
Higher scores indicate poorer functioning; scores ≥2 reflect impaired functioning in that domain. Results are reported for the total sum with full range from 3 (no impairment) to 60 (severe impairment), which is based on all individual domain scores.
Time Frame
At baseline and Visit 6 (week 10)
Title
Sheehan Disability Scale
Description
The Sheehan Disability Scale (SDS) is a self-rated scale which assesses illness-related disability in three areas of functioning: work, social and family. The SDS assess disability or functional impairment across three domains: work/school, social life/leisure activities and family life/home responsibilities. Each domain is scored from 0 (not at all) to 10 (very severely). The three domains can be summarized to evaluate global functional impairment by adding the scores of each of the three domains, resulting in global SDS score ranges from 0 (unimpaired) to 30 (highly impaired).
Time Frame
At baseline and Visit 6 (week 10)
Title
Patient Rated Inventory of Side Effects (PRISE)
Description
Frequency of observed adverse events over the study treatment period as captured by the PRISE. The Patient Rated Inventory of Side Effects (PRISE) assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other).
Time Frame
up to 12 weeks
Title
Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a comprehensive, semi-structured interview measure that uniquely measures the full spectrum of suicidality including passive and active suicidal ideation, suicidal intent as well as suicidal behaviors. Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).
Time Frame
up to 12 weeks
Title
Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR)
Description
The Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR) is a 16-item self rated instrument designed to assess the severity of depressive symptoms (30). The 16 items cover the nine symptom domains of major depression, and are rated on a scale of 0-3. Total score ranges from 0 to 27, with ranges of 0-5 (normal), 6-10 (mild), 11-15 (moderate), 16-20 (moderate to severe), and 21+ (severe).
Time Frame
up to 12 weeks
Title
Clinical Global Impression (CGI) Scale
Description
The Clinical Global Impression (CGI) scale assesses overall treatment response in psychiatric patients and has good reliability and validity metrics. The administration time is 2 minutes. This scale consists of three items: Severity of Illness (item 1); Global Improvement (item 2); and Efficacy Index (item 3). Item 1 is rated on a seven-point scale (1 = normal, 7 = among the most extremely ill patients) as is item 2 (1 = very much improved, 7 = very much worse). Full scale is 1 to 14.
Time Frame
up to 12 weeks
Title
Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ)
Description
The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) is a brief scale to measure cognitive and executive dysfunction in mood and anxiety disorders, and possesses good reliability and validity. The Massachusetts General Hospital CPFQ was developed to assess each of the 7 most common complaints of depressed patients reporting fatigue or cognitive/executive problems. The CPFQ consists of 7 questions, each rated on a scale from 1 to 6, with 1 indicating greater than normal functioning, 2 indicating normal functioning and with higher numbers indicating poorer functioning. Total score range from 7 (greater than normal function) to 42 (poor function).
Time Frame
At baseline and Visit 6 (week 10)
Title
HAM-A
Description
Change in Hamilton Anxiety Rating Scale (HAM-A) score from baseline to Week 10. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and >25-30 moderate to severe.
Time Frame
Baseline and Week 10
Title
Beck Scale for Suicidal Ideation (BSI)
Description
Mean change in Brief Inventory Symptom from baseline to week 10. The BSS is a self-report 19-item scale preceded by five screening items. The BSS and its screening items are intended to assess a patient's thoughts, plans and intent to commit suicide. All 24 items are rated on a three-point scale (0 to 2). In this study, scores from the five screening items were included in the overall score. Therefore, total scores could range from 0 to 48, with higher scores reflecting more severe symptoms.
Time Frame
Baseline and Week 10
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female participants, 18-65 years of age;
Current primary Axis I diagnosis of major depressive disorder according to DSM-IV-TR criteria as determined by a psychiatrist and confirmed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID);
Current treatment-resistant depression defined by a history of inadequate response to a minimum of 2 adequate antidepressant treatment trials determined by patient history and chart review and confirmed with the Antidepressant Treatment History Form (ATHF);
Participants must be willing to discontinue treatment with concomitant medications that are disallowed by the study protocol;
Participants must have a level of understanding of the English language sufficient to agree to all tests and examinations required by the study and must be able to participate fully in the informed consent process.
Exclusion Criteria:
Lifetime diagnosis of schizophrenia or any psychotic disorder, bipolar disorder, pervasive developmental disorders or mental retardation
Diagnosis of a substance use disorder within the past 1 year ;
Female participants who are pregnant, nursing, for may become pregnant;
Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
Participants with clinically significant abnormalities of laboratories, physical examination, or ECG;
Prolonged QT interval, congenital long QT syndrome, history suggestive of torsades de pointes, or heart failure;
Complete atrioventricular (AV) block without implanted pacemaker, or patients at high risk of complete AV block
Participants with a history of quinidine, quinine or mefloquine-induced thrombocytopenia, hepatitis, or other hypersensitivity reactions;
Participants judged to be at serious suicidal risk by the PI;
Concomitant use with quinidine, quinine, or mefloquine;
Participants with known hypersensitivity to dextromethorphan;
Use with an MAOI or within 14 days of stopping an MAOI;
Concomitant use with drugs that prolong QT interval and are metabolized by CYP2D6
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Murrough, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
28478356
Citation
Murrough JW, Wade E, Sayed S, Ahle G, Kiraly DD, Welch A, Collins KA, Soleimani L, Iosifescu DV, Charney DS. Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial. J Affect Disord. 2017 Aug 15;218:277-283. doi: 10.1016/j.jad.2017.04.072. Epub 2017 Apr 29.
Results Reference
result
Links:
URL
http://www.mssm.edu/map
Description
Mood and Anxiety Disorders Program
Learn more about this trial
Nuedexta in Treatment-Resistant Major Depression
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