Treatment-Resistant Depression Registry

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cyberonics, Inc.
ClinicalTrials.gov Identifier:
NCT00320372
First received: May 1, 2006
Last updated: December 22, 2015
Last verified: December 2015
  Purpose
This registry will collect information about patients with treatment-resistant depression (TRD) who are currently in a major depressive episode. For the purposes of this study, TRD is defined as an ongoing depression lasting at least 2 years or that has recurred at least 3 times, to include the current episode, during the patient's lifetime AND has not adequately responded to 4 or more adequate antidepressive treatments. The registry will follow the clinical course and outcomes for patients with TRD who are treated with and without adjunctive (used along with other treatments for depression) vagus nerve stimulation (VNS) therapy.

Condition
Major Depressive Disorder

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: A Long-term, Prospective, Observational, Multi-center Patient Outcome Registry to Collect Data in Patients With Treatment-resistant Depression (TRD) Who Are Currently in a Major Depressive Episode.

Further study details as provided by Cyberonics, Inc.:

Primary Outcome Measures:
  • Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline) [ Time Frame: 3-Month Through 60-Month (Post Baseline) ] [ Designated as safety issue: No ]

    Response Rate was computed and summarized as the proportion of patients that achieved ≥ 50% reduction from baseline in MADRS total score at each post-baseline visit. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The lower a score the less symptom severity is seen. A patient was considered a "Responder" (Yes = 1) if achieved ≥ 50% reduction from baseline in MADRS total score at visit month assessment post-baseline. A "Non-Responder" (No = 0) was any patient who did not achieve ≥ 50% reduction from baseline in MADRS score at visit month assessment post-baseline.

    Total number of patients in each group may be lower than ITT in a case of missing assessment data.



Secondary Outcome Measures:
  • Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: 3-Month Through 60-Month (Post Baseline) ] [ Designated as safety issue: No ]

    Recurrence based on MADRS is defined as first time attained MADRS total score ≥ 20 after achieving remission. Remission is a binary outcome response variable (Yes/No in-remission) defined as MADRS total score </= 9 at visit month assessment post-baseline. Duration of remission Computed as recorded date of the first recurrence/relapse (MADRS score >/= 20) minus the recorded date of first achieved remission (MADRS score </=9). Only a subpopulation that achieved remission will be included in the summary.

    Time-to-event analyses were summarized using Kaplan-Meier curves. Patients who did not achieve recurrence at the end of the study were censored on the last visit date recorded. Additionally, patients who discontinued early were censored on last date of contact. Censored observations and confidence intervals for the estimated median times were calculated.


  • Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline) [ Time Frame: 3-Month Through 60-Month (Post Baseline) ] [ Designated as safety issue: No ]
    Remission is a binary outcome response variable (Yes/No Inremission) defined as MADRS total score < 9 at visit month assessment post-baseline. The MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The lower a score the less symptom severity is seen and in general it is accepted that a score between 0-6 is indicative of a normal/symptom-free individual; 7-19 is indicative of a patient with mild depression; 20-34 is indicative of a patient with moderate depression; and >34 is indicative of a patient with severe depression. Total number of patients in each group may be lower than ITT in a case of missing assessment data.

  • Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation [ Time Frame: 1 Week Pre-Baseline ] [ Designated as safety issue: No ]

    This assessment was completed telephonically by a third party rater (Central Rater Group). The rating was based on a clinical interview moving from broadly phrased questions about symptoms to more detailed ones, which allowed a precise rating of severity. The rater decided whether the rating lied on the defined scale steps (0, 2, 4, 6) or between them (1, 3, 5) and then checked the appropriate selection on the MADRS Item 10 Suicidal Thoughts (Ideation).

    Total number of patients analyzed may be lower than ITT in a case of missing assessment data.


  • Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    This assessment was completed by the physician at the baseline visit in a clinical interview. The physician decided which category (as shown in outcome measure data table) best characterized the patient's medical threat to life of their most recent suicidal gesture or attempt.

    Total number of patients analyzed may be lower than ITT in a case of missing assessment data.


  • Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture [ Time Frame: Baseline ] [ Designated as safety issue: No ]

    This assessment was completed by the physician at the baseline visit in a clinical interview. The physician decided which category (as shown in outcome measure data table) best characterized the patient's intent of their most recent suicidal gesture or attempt.

    Total number of patients analyzed may be lower than ITT in a case of missing assessment data.


  • Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE [ Time Frame: Screening ] [ Designated as safety issue: No ]
    This assessment was completed by the physician at the screening visit. The physician decided which DSM-IV Diagnosis (as shown in outcome measure data table) best characterized the patient's primary diagnosis of MDE.


Enrollment: 795
Study Start Date: January 2006
Study Completion Date: May 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
1. 500 VNS Patients
VNS Patients - Treatment-resistant depression patients treated with VNS Therapy.
2. 300 Non-VNS Patients
Non-VNS Patients - Treatment-resistant depression patients not receiving VNS Therapy.

Detailed Description:

Enrollment of TRD patients treated with VNS Therapy will consist of patients originally enrolled in the registry as well as patients who have completed the D-21 Dosing Study and are enrolled in the Registry for Long-Term Follow-up. Sites will maintain a screening log of all patients who have been screened for original TRD Registry patients.

Please note that because this is a post-approval registry, Cyberonics does not cover the cost of VNS Therapy implantation.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with chronic depression that is at least two years in duration or a recurrent depression that includes at least three lifetime episodes including the current major depressive episode (MDE); and an inadequate response to four or more adequate antidepressant treatments.
Criteria

Inclusion Criteria:

  • Patient diagnosed with a current major depressive episode according to DSM-IV-TR criteria.
  • For D-21 patients only who have completed the D-21 dosing Study without any D-21 inclusion and exclusion protocol deviation.
  • Patient has been in the current depressive episode for 2 years or longer, or has had at least 3 lifetime episodes including the current MDE.
  • Patient has had an inadequate response to 4 or more adequate antidepressive treatments.
  • The patient has a CGI severity of illness score of moderately ill (score of 4) or greater.
  • The patient must be able to provide informed consent and complete all forms.

Exclusion Criteria:

  • Patient has a history of schizophrenia, schizoaffective disorder, any other psychotic disorder, or a current major depressive episode that includes psychotic features; or is currently psychotic.
  • Patient is currently enrolled in a double blind investigational study; patients who have completed the double-blind D-21 study will be allowed to enter the Registry for Long Term Follow-up
  • Other than those patients who were enrolled in the D-21 study, patient has previously received VNS therapy.
  • Patient has a history of rapid cycling bipolar disorder.
  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: NCT00320372

  Show 55 Study Locations
Sponsors and Collaborators
Cyberonics, Inc.
Investigators
Principal Investigator: Adam K. Ashton, MD Suburban Psychiatric Associates
Principal Investigator: Herbert Ward, MD University of Florida
Principal Investigator: Thomas Schwartz, MD SUNY UMU at Syracuse
Principal Investigator: Mark Zetin, MD Private Practice
Principal Investigator: Darin D. Dougherty, MD Massachusetts General Hospital
Principal Investigator: George Keepers, MD Oregon Health and Science University
Principal Investigator: Mustafa M. Husain, MD UT Southwestern Medical Center at Dallas
Principal Investigator: Leighton Y. Huey, MD University of Connecticut Health Center
Principal Investigator: James Kimball, MD Wake Forest School of Medicine
Principal Investigator: Peter J. Holland, MD Florida Atlantic University
Principal Investigator: Robert Howland, MD Western Psychiatric Institute & Clinic (WPIC)
Principal Investigator: Anthony Rothschild, MD University of Massachusetts, Worcester
Principal Investigator: Craig J Vine, MD Psychiatric Recovery
Principal Investigator: Joel Young, MD Rochester Center for Behavioral Science
Principal Investigator: Lawrence W Adler, MD Clinical Insights
Principal Investigator: Harold Harsch, MD Medical College of Wisconsin
Principal Investigator: Syed Ali, MD Dupage Mental Health Services
Principal Investigator: Keming Gao, MD University Hospital Case Medical Center
Principal Investigator: Todd M. Antin, M.D., DFAPA Pact Atlanta, LLC
Principal Investigator: Basanti Basu, M.D. Century Health
Principal Investigator: Dwight Bearden, MD Private Practice
Principal Investigator: David L. Dunner, MD Center for Anxiety and Depression
Principal Investigator: Azfar Malik, MD Psych Care Consultants Research
Principal Investigator: Joel Morgan, MD Valdosta Psychiatric Associates LLC
Principal Investigator: Mark George, MD Medical University of South Carolina
Principal Investigator: Frederick W. Reimherr, MD Psychiatric & Behavorial Solutions
Principal Investigator: John Zajecka, MD Psychiatric Medicine Associates, LLC
Principal Investigator: Michael Banov, MD Northwest Behavioral Research Center
Principal Investigator: Robert Lehman, MD Pharmasite Research, Inc.
Principal Investigator: Scott Aaronson, MD Sheppard Pratt Health Systems, Inc.
Principal Investigator: Jaishree Narayanan, MD NorthShore University HealthSystem
Principal Investigator: Greg Seal, MD Louisiana Clinical Research, LLC
Principal Investigator: Horacio Capote, MD Dent Neurologic Institute
Principal Investigator: Charles Conway, MD Washington University School of Medicine
Principal Investigator: Michael Lesem, MD Claghorn-Lesem Reserach Clinic, Ltd.
Principal Investigator: Miguel Martelli, MD MG Martelli, MD, PC and Associates
Principal Investigator: Ananda Pandurangi, MD Virginia Commonwealth University
Principal Investigator: Peter Thompson, MD The University of Texas Health Science Center at San Antonio
Principal Investigator: Theodore Goodman, MD Sutter Institute for Medical Research
Principal Investigator: Francisco Moreno, MD University of Arizona
Principal Investigator: Martha Edelman, MD Jamaica Hospital Medical Center
Principal Investigator: Peter Bulow, MD Columbia University
Study Director: Mark Bunker Cyberonics, Inc.
Principal Investigator: Mahendra Bhati, MD University of Pennsylvania
Principal Investigator: Ronald Warnell, MD Loma Linda University
Principal Investigator: Robert Cohen, MD Cedars-Sinai Hospital
Principal Investigator: Janak Mehtani, MD Fair Oaks Psychiatric Associates
Principal Investigator: Mounir Soliman, MD University of California, San Diego
Principal Investigator: Francisco Fernandez, MD University of South Florida
Principal Investigator: Arthur Holt, MD Arthur Holt, Private Practice
Principal Investigator: Harold McGrath, MD McGarth Clinic
Principal Investigator: Anthony D'Agostino, MD Alexian Brothers Behavioral Health Hospital
Principal Investigator: Anne Gilbert, MD 3c Methodist Hospital
Principal Investigator: Michael Burke, MD Clinical Research Institute
Principal Investigator: Ed Coffey, MD Henry Ford Health Services
Principal Investigator: Joseph Kwentus, MD University of Mississippi Medical Center
Principal Investigator: David Ginsberg, MD New York University of Medical Center
Principal Investigator: Melissa Martinez, MD Baylor College of Medicine
Principal Investigator: Arnold Mech, MD The Mech Center
Principal Investigator: Joseph Simpson, MD Alamo Superior Research
  More Information

Publications:
Responsible Party: Cyberonics, Inc.
ClinicalTrials.gov Identifier: NCT00320372     History of Changes
Obsolete Identifiers: NCT00657215
Other Study ID Numbers: TRD Registry 
Study First Received: May 1, 2006
Results First Received: December 18, 2015
Last Updated: December 22, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Cyberonics, Inc.:
Major Depressive Disorder
Treatment-resistant Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 29, 2016