Nuedexta in Treatment-Resistant Major Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Mount Sinai School of Medicine
Sponsor:
Information provided by (Responsible Party):
James Murrough, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01882829
First received: June 14, 2013
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Treatment Resistant
Drug: dextromethorphan/quinidine
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • 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)



Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 20
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)
Arms Assigned Interventions
Experimental: Nuedexta (dextromethorphan/quinidine)
45/10 mg every 12 hours x 8 weeks
Drug: dextromethorphan/quinidine
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01882829

Contacts
Contact: Sehrish Moughal Sayed 212-241-3142 seharish.moughal@mssm.edu

Locations
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Principal Investigator: James Murrough, MD         
Sponsors and Collaborators
James Murrough
Investigators
Principal Investigator: James Murrough, MD Mount Sinai School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: James Murrough, Assistant Professor, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01882829     History of Changes
Other Study ID Numbers: GCO 13-0389, IF1463152
Study First Received: June 14, 2013
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
depression
major depressive disorder
treatment resistant
Nuedexta
dextromethorphan
antidepressant
glutamate
NMDA receptor

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Dextromethorphan
Quinidine
Quinidine gluconate
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antitussive Agents
Respiratory System Agents
Anti-Arrhythmia Agents
Cardiovascular Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 26, 2014