Clinical trial NCT00320372: Treatment-Resistant Depression Registry
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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Major Depressive Disorder
Keywords: Major Depressive Disorder
Treatment-resistant Depression
Lead sponsor: Cyberonics, Inc.
Sponsor class: INDUSTRY
First posted: 2006-05-03
Enrollment: 795
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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 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.

Primary outcomes:
measure: Montgomery Asberg Depression Rating Scale (MADRS)% Responders (>/= 50% Improvement From Baseline)
timeFrame: 3-Month Through 60-Month (Post Baseline)
Secondary outcomes:
measure: Time Until Recurrence (TUR) for Patients That Achieved Remission, Based on Montgomery Asberg Depression Rating Scale (MADRS)
timeFrame: 3-Month Through 60-Month (Post Baseline)
measure: Montgomery Asberg Depression Rating Scale (MADRS)% Remitters (MADRS Total Score ≤9 at Visit Month Assessment Post-Baseline)
timeFrame: 3-Month Through 60-Month (Post Baseline)
measure: Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Baseline MADRS Item 10 Suicidal Ideation
timeFrame: 1 Week Pre-Baseline
measure: Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Medical Threat to Life of Most Recent Suicidal Gesture
timeFrame: Baseline
measure: Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Intent of Most Recent Suicidal Gesture
timeFrame: Baseline
measure: Predictors of Suicidality Based on Montgomery Asberg Depression Rating Scale (MADRS) Item 10 Score - Primary Diagnosis of MDE
timeFrame: Screening
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Beverly Hills
country: United States
facility: Cedars-Sinai Hospital
state: California
city: Garden Grove
country: United States
facility: Mark Zetin, MD - Private Practice
state: California
city: Loma Linda
country: United States
facility: Loma Linda University
state: California
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: Sacramento
country: United States
facility: Fair Oaks Psychiatric Associates
state: California
city: Farmington
country: United States
facility: University of Connecticut Health Center
state: Connecticut
city: Boca Raton
country: United States
facility: Florida Atlantic University
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Brunswick
country: United States
facility: MG Martelli, MD, PC and Associates
state: Georgia
city: Columbus
country: United States
facility: Arthur Holt, Private Practice
state: Georgia
city: Decatur
country: United States
facility: Pact Atlanta, LLC
state: Georgia
city: Macon
country: United States
facility: Private Practice
state: Georgia
city: Marietta
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Valdosta
country: United States
facility: Valdosta Psychiatric Associates LLC
state: Georgia
city: Evanston
country: United States
facility: Northshore University Health System
state: Illinois
city: Evergreen Park
country: United States
facility: McGrath Clinic
state: Illinois
city: Hoffman Estates
country: United States
facility: Alexian Brothers Behavioral Health Hospital
state: Illinois
city: Skokie
country: United States
facility: Psychiatric Medicine Associates, LLC
state: Illinois
city: Wheaton
country: United States
facility: Dupage Mental Health Services
state: Illinois
city: Indianapolis
country: United States
facility: 3c Methodist Hospital
state: Indiana
city: Wichita
country: United States
facility: Clinical Research Institute
state: Kansas
city: Shreveport
country: United States
facility: Louisiana Clinical Research, LLC
state: Louisiana
city: Baltimore
country: United States
facility: Pharmasite Research Inc.
state: Maryland
city: Baltimore
country: United States
facility: Sheppard Pratt Health Systems, Inc.
state: Maryland
city: Glen Burnie
country: United States
facility: Clinical Insights
state: Maryland
city: Charlestown
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Rochester Hills
country: United States
facility: Rochester Center for Behavioral Medicine
state: Michigan
city: St. Paul
country: United States
facility: Psychiatric Recovery
state: Minnesota
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: St. Louis
country: United States
facility: Psych Care Consultants Research
state: Missouri
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: Amherst
country: United States
facility: Suburban Psychiatric Associates
state: New York
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Syracuse
country: United States
facility: SUNY UMU at Syracuse
state: New York
city: Winston Salem
country: United States
facility: Wake Forest University - Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Findlay
country: United States
facility: Century Health
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Psychiatric Institute & Clinic (WPIC)
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Houston
country: United States
facility: Claghorn-Lesem Reserach Clinic, Ltd.
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Plano
country: United States
facility: The Mech Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Alamo Superior Research
state: Texas
city: Salt Lake City
country: United States
facility: Psychiatric & Behavioral Solutions
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Mercer Island
country: United States
facility: Center for Anxiety and Depression
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Suburban Psychiatric Associates
name: Adam K. Ashton, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Herbert Ward, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SUNY UMU at Syracuse
name: Thomas Schwartz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Private Practice
name: Mark Zetin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Darin D. Dougherty, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oregon Health and Science University
name: George Keepers, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UT Southwestern Medical Center at Dallas
name: Mustafa M. Husain, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: UConn Health
name: Leighton Y. Huey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wake Forest University Health Sciences
name: James Kimball, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Florida Atlantic University
name: Peter J. Holland, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Western Psychiatric Institute & Clinic (WPIC)
name: Robert Howland, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Massachusetts, Worcester
name: Anthony Rothschild, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Psychiatric Recovery
name: Craig J Vine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rochester Center for Behavioral Science
name: Joel Young, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Insights
name: Lawrence W Adler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Harold Harsch, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dupage Mental Health Services
name: Syed Ali, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospitals Cleveland Medical Center
name: Keming Gao, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pact Atlanta, LLC
name: Todd M. Antin, M.D., DFAPA
role: PRINCIPAL_INVESTIGATOR
affiliation: Century Health
name: Basanti Basu, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Private Practice
name: Dwight Bearden, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Anxiety and Depression
name: David L. Dunner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Psych Care Consultants Research
name: Azfar Malik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Valdosta Psychiatric Associates LLC
name: Joel Morgan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Mark George, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Psychiatric & Behavorial Solutions
name: Frederick W. Reimherr, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Psychiatric Medicine Associates, LLC
name: John Zajecka, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwest Behavioral Research Center
name: Michael Banov, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pharmasite Research, Inc.
name: Robert Lehman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sheppard Pratt Health Systems, Inc.
name: Scott Aaronson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Endeavor Health
name: Jaishree Narayanan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Louisiana Clinical Research, LLC
name: Greg Seal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dent Neurologic Institute
name: Horacio Capote, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Washington University School of Medicine
name: Charles Conway, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Claghorn-Lesem Reserach Clinic, Ltd.
name: Michael Lesem, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: MG Martelli, MD, PC and Associates
name: Miguel Martelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Virginia Commonwealth University
name: Ananda Pandurangi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Texas Health Science Center at San Antonio
name: Peter Thompson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sutter Institute for Medical Research
name: Theodore Goodman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Arizona
name: Francisco Moreno, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jamaica Hospital Medical Center
name: Martha Edelman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Peter Bulow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cyberonics, Inc.
name: Mark Bunker
role: STUDY_DIRECTOR
affiliation: University of Pennsylvania
name: Mahendra Bhati, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Loma Linda University
name: Ronald Warnell, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Hospital
name: Robert Cohen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fair Oaks Psychiatric Associates
name: Janak Mehtani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Mounir Soliman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of South Florida
name: Francisco Fernandez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arthur Holt, Private Practice
name: Arthur Holt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McGarth Clinic
name: Harold McGrath, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alexian Brothers Behavioral Health Hospital
name: Anthony D'Agostino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 3c Methodist Hospital
name: Anne Gilbert, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Institute
name: Michael Burke, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Health Services
name: Ed Coffey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Mississippi Medical Center
name: Joseph Kwentus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York University of Medical Center
name: David Ginsberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Melissa Martinez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Mech Center
name: Arnold Mech, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Alamo Superior Research
name: Joseph Simpson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM, Lavori P, Howland R, Kling MA, Rittberg B, Carpenter L, Ninan P, Moreno F, Schwartz T, Conway C, Burke M, Barry JJ. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry. 2005 Sep 1;58(5):355-63. doi: 10.1016/j.biopsych.2005.05.024.
citation: Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005 Sep 1;58(5):347-54. doi: 10.1016/j.biopsych.2005.05.025.
citation: George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, Howland R, Kling MA, Moreno F, Rittberg B, Dunner D, Schwartz T, Carpenter L, Burke M, Ninan P, Goodnick P. A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry. 2005 Sep 1;58(5):364-73. doi: 10.1016/j.biopsych.2005.07.028.
citation: Bajbouj M, Merkl A, Schlaepfer TE, Frick C, Zobel A, Maier W, O'Keane V, Corcoran C, Adolfsson R, Trimble M, Rau H, Hoff HJ, Padberg F, Muller-Siecheneder F, Audenaert K, van den Abbeele D, Matthews K, Christmas D, Eljamel S, Heuser I. Two-year outcome of vagus nerve stimulation in treatment-resistant depression. J Clin Psychopharmacol. 2010 Jun;30(3):273-81. doi: 10.1097/JCP.0b013e3181db8831.
citation: McAllister-Williams RH, Sousa S, Kumar A, Greco T, Bunker MT, Aaronson ST, Conway CR, Rush AJ. The effects of vagus nerve stimulation on the course and outcomes of patients with bipolar disorder in a treatment-resistant depressive episode: a 5-year prospective registry. Int J Bipolar Disord. 2020 May 2;8(1):13. doi: 10.1186/s40345-020-0178-4.
citation: Aaronson ST, Sears P, Ruvuna F, Bunker M, Conway CR, Dougherty DD, Reimherr FW, Schwartz TL, Zajecka JM. A 5-Year Observational Study of Patients With Treatment-Resistant Depression Treated With Vagus Nerve Stimulation or Treatment as Usual: Comparison of Response, Remission, and Suicidality. Am J Psychiatry. 2017 Jul 1;174(7):640-648. doi: 10.1176/appi.ajp.2017.16010034. Epub 2017 Mar 31.