Clinical trial NCT00305565: Study Comparing Outcomes for Patients With Treatment Resistant Depression Who Receive VNS Therapy at Different Doses
Official title: Randomized Comparison of Outcomes in Patients With Treatment-Resistant Depression Who Receive VNS Therapy Administered at Different Amounts of Electrical Charge
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Keywords: Depression
Chronic Depression
Bipolar Disorder
Lead sponsor: Cyberonics, Inc.
Sponsor class: INDUSTRY
First posted: 2006-03-22
Enrollment: 331
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a postmarket medical device study. The objective of this study is to compare the safety and effectiveness of Vagus Nerve Stimulation (VNS) Therapy administered at different amounts of electrical charge for the treatment of patients with treatment-resistant depression (TRD).

Detailed description: This is a postmarket medical device study. This study will examine treatment outcomes for patients with TRD who are randomized to VNS Therapy administered at different amounts of electrical charge. The Sponsor, Cyberonics, provides funding for this study. Patients are followed for 54 weeks, 50 of those weeks are following implantation of the VNS Therapy system. No study sites will be permitted to enroll study subjects until Institutional Review Board (IRB) approval has been received. Sites are permitted to be approved by a local or a central IRB.

Eligibility criteria: Inclusion Criteria:

* Patient has a diagnosis of chronic or recurrent depression and is currently experiencing a major depressive episode.
* Patient has not had an adequate response to four or more adequate antidepressant treatments from at least two different antidepressant treatment categories.
* Patient has (in the investigator's judgment) sufficient impairment from his/her depression and/or depression treatment that the potential benefits/risks of VNS Therapy are warranted.
* Patient must currently be receiving at least one antidepressant treatment; the patient must be receiving all current antidepressant treatments in a stable regimen.
* If the patient has a current diagnosis of bipolar disorder, the patient must be receiving a mood stabilizer.
* Patient must be 18 years of age or older and of legal age of consent.
* Patient must be able to complete the evaluations specified in the study procedures flow chart.
* Patient must provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization.

Exclusion Criteria:

* Patient has had a bilateral or left cervical vagotomy.
* Patient currently uses, or is expected to use during the study, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy.
* A VNS Therapy System implant would pose an unacceptable surgical or medical risk for the patient.
* Patient is expected to require full body magnetic resonance imaging during the clinical study.
* Patient is acutely suicidal.
* Patient has a history of schizophrenia, schizoaffective disorder, or other psychotic disorder or a current major depressive episode that includes psychotic features (commonly referred to as psychotic depression).
* Patient has a history of rapid cycling bipolar disorder or a current diagnosis of bipolar disorder mixed phase.
* Patient has a history of borderline personality disorder.
* Patient has a history of drug or alcohol dependence within the 12 months prior to the baseline visit or currently takes a narcotic drug five or more days per week.
* Patient is currently enrolled in another investigational study.
* Patient has had a prior VNS Therapy System implant.

Note: Some IRBs may require additional conditions for enrollment.

Primary outcomes:
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From Baseline to Study Week 22
Secondary outcomes:
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population).
timeFrame: From Baseline to Study Week 50
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population)
timeFrame: At Study Week 22
measure: Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population).
timeFrame: At Study Week 50
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population).
timeFrame: From baseline to Study Week 22
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
measure: Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population).
timeFrame: From baseline to Study Week 50
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Sacramento
country: United States
facility: Sutter Institute for Medical Research
state: California
city: Marietta
country: United States
facility: Northwest Behavioral Research Center
state: Georgia
city: Evanston
country: United States
facility: Evanston Northwestern Hospital
state: Illinois
city: Wichita
country: United States
facility: Clinical Research Institute
state: Kansas
city: Shreveport
country: United States
facility: Brentwood Research Institute
state: Louisiana
city: Baltimore
country: United States
facility: Sheppard Pratt Hospital
state: Maryland
city: Baltimore
country: United States
facility: Pharmasite Research Inc.
state: Maryland
city: Charlestown
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: St. Paul
country: United States
facility: Psychiatric Recovery
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis University
state: Missouri
city: Amherst
country: United States
facility: Dent Neurologic Institute
state: New York
city: New York
country: United States
facility: Eastside Comprehensive Medical Center
state: New York
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: Austin
country: United States
facility: Community Clinical Research, Inc.
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Claghorn-Lesem Research Clinic, LTD
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Mercer Island
country: United States
facility: Center for Anxiety and Depression
state: Washington
Study officials:
affiliation: Cyberonics, Inc.
name: Mark Bunker, PharmD
role: STUDY_DIRECTOR
References:
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citation: Murray CJ, Lopez AD. Evidence-based health policy--lessons from the Global Burden of Disease Study. Science. 1996 Nov 1;274(5288):740-3. doi: 10.1126/science.274.5288.740. No abstract available.
citation: Geddes LA, Baker LE: Principles of Applied Biomedical Instrumentation, third edition. New York; John Wiley & Sons, 1989; 458-461.
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: 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: 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: Aaronson ST, Carpenter LL, Conway CR, Reimherr FW, Lisanby SH, Schwartz TL, Moreno FA, Dunner DL, Lesem MD, Thompson PM, Husain M, Vine CJ, Banov MD, Bernstein LP, Lehman RB, Brannon GE, Keepers GA, O'Reardon JP, Rudolph RL, Bunker M. Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects. Brain Stimul. 2013 Jul;6(4):631-40. doi: 10.1016/j.brs.2012.09.013. Epub 2012 Oct 23.