Nuedexta in Treatment-Resistant Major Depression
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.
Major Depressive Disorder
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Targeting the NMDA Glutamate Receptor as Novel Antidepressant Strategy: A Pilot Clinical Trial of Nuedexta in Treatment-Resistant Major Depression|
- Change in Montgomery-Asberg Depression Rating Scale [ Time Frame: At baseline and visit 6 (week 10) ] [ Designated as safety issue: No ]
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 rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 and 60 points. The MADRS is specifically designed to detect changes in depression severity in the context of a medication treatment trial and is the used as the primary outcome of the current study.
Primary outcome is change in MADRS at Visit 6 (Week 10)
- Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form [ Time Frame: At baseline and Visit 6 (week 10) ] [ Designated as safety issue: No ]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.
- Change in Range of Impaired Functioning Tool [ Time Frame: At baseline and Visit 6 (week 10) ] [ Designated as safety issue: No ]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.
- Change in Sheehan Disability Scale [ Time Frame: At baseline and Visit 6 (week 10) ] [ Designated as safety issue: No ]The Sheehan Disability Scale is a self-rated scale which assesses illness-related disability in three areas of functioning: work, social and family.
- Patient Rated Inventory of Side Effects (PRISE) [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]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) [ Time Frame: up to 12 weeks ] [ Designated as safety issue: Yes ]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.
- Quick Inventory of Depressive Symptomatology, Self Report (QIDS-SR) [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]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 [ Time Frame: up to 12 weeks ] [ Designated as safety issue: No ]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).
- Change in Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) [ Time Frame: At baseline and Visit 6 (week 10) ] [ Designated as safety issue: No ]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.
|Study Start Date:||July 2013|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Nuedexta (dextromethorphan/quinidine)
45/10 mg every 12 hours x 8 weeks
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
Other Name: Nuedexta
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01882829
|Contact: Sehrish Moughal Sayedfirstname.lastname@example.org|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Principal Investigator: James Murrough, MD|
|Principal Investigator:||James Murrough, MD||Mount Sinai School of Medicine|