Study Comparing Outcomes for Patients With Treatment Resistant Depression Who Receive VNS Therapy at Different Doses

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Comparison of Outcomes in Patients With Treatment-Resistant Depression Who Receive VNS Therapy Administered at Different Amounts of Electrical Charge

Conditions
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Depression

Intervention / Treatment
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* Device: VNS Therapy
* Device: VNS Therapy
* Device: VNS Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Low Dose<br> | Device: VNS Therapy<br>* Received output current of 0.25 milliamps (mA)<br>* Other names: VNS Therapy System;|
| Other: Medium Dose<br> | Device: VNS Therapy<br>* Received output current of 0.5-1.0 mA<br>* Other names: VNS Therapy System;|
| Other: High Dose<br> | Device: VNS Therapy<br>* Received output current of 1.0-1.5 mA<br>* Other names: VNS Therapy System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. | From Baseline to Study Week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 22 | 
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C. | From baseline to Study Week 22 | 
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 50 | 
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Sustained Responders at Study Week 50 (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the IDS-C to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy. | From baseline to Study Week 50 | 
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C. | From baseline to Study Week 50 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 22 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of remitters at week 22. Remission was defined as a score of less than or equal to 5 on the QIDS-C. | From baseline to Study Week 22 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 50 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C percent of remitters at week 50. Remission was defined as a score of less than or equal to 5 on the QIDS-C. | From baseline to Study Week 50 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 22 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of remitters at week 22. Remission was defined as a score of less than or equal to 9 on the MADRS. | From baseline to Study Week 22 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 50 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Sustained Responders at Study Week 50 (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. Sustained Response is defined as the percentage of Acute Phase responders (week 22) who were also responders at the end of the Long-term (week 50) phase. An analysis of sustained response was performed using the MADRS to evaluate the long-term durability of the improvements in depression scores observed with adjunctive VNS Therapy. | From Baseline to Study Week 50 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS percent of remitters at week 50. Remission was defined as a score of less than or equal to 9 on the MADRS. | From baseline to Study Week 50 | 
| Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 22 of the Acute Phase (ITT Population) | Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.) In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit. | At Study Week 22 | 
| Clinical Global Impressions Improvement Scale (CGI-I) Percent Response at Week 50 of the Long-term Phase (ITT Population). | Originally, the Clinical Global Impressions-Improvement (CGI-I) (Guy W 1976)was designed as a 7-item scale used to assess how much the patient's illness had improved or worsened relative to a baseline state at the beginning of the intervention.(1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.) In this study, the CGI-I was categorized into just two groups. A value of 1 (considered a response) was assigned for very much improved (at least 85% improvement) & much improved (at least 60% improvement). A value of 0 (considered non-response) was assigned for: minimally improved (at least 20-25% improvement), no change (between ±15% change), minimally worse (at least 20-55% worse), much worse (at least 60% worse), and very much worse (at least 80% worse). No score was assigned if the investigator did not provide a categorical rating at a particular follow-up visit. | At Study Week 50 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of responders at week 22. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 22 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of remitters at week 22. Remission was defined as a score of less than or equal to 14 on the IDS-C. | From baseline to Study Week 22 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Responders From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of responders at week 50. Response was defined as greater than or equal to 50% improvement from baseline. | From baseline to Study Week 50 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Percent Remitters From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR percent of remitters at week 50. Remission was defined as a score of less than or equal to 14 on the IDS-C. | From baseline to Study Week 50 | 
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean percent change at week 22 | From baseline to Study Week 22 | 
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean change at week 50 | From baseline to Study Week 50 | 
| Inventory of Depressive Symptomatology-Clinician Administered (IDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-C mean percent change at week 50 | From baseline to Study Week 50 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean change at week 22 | From baseline to Study Week 22 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean percent change at week 22 | From baseline to Study Week 22 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean change at week 50 | From baseline to Study Week 50 | 
| Quick Inventory of Depressive Symptomatology-Clinician Administered (QIDS-C) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 16-item Inventory of Depressive Symptomatology (QIDS) (Rush et al. 2003) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 27. Higher values are considered to be worse outcomes. The QIDS-C mean percent change at week 50 | From baseline to Study Week 50 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean change at week 22 | From baseline to Study Week 22 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean percent change at week 22 | From baseline to Study Week 22 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean change at week 50 | From baseline to Study Week 50 | 
| Montgomery-Asberg Depression Rating Scale (MADRS) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 10-item Montgomery-Asberg Scale (Montgomery and Asberg 1979) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 60. Higher values are considered to be worse outcomes. The MADRS mean percent change at week 50 | From baseline to Study Week 50 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean change at week 22 | From baseline to Study Week 22 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 22 of the Acute Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean percent change at week 22 | From baseline to Study Week 22 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean change at week 50 | From baseline to Study Week 50 | 
| Inventory of Depressive Symptomatology Self-Report (IDS-SR) Mean Percent Change From Baseline to Week 50 of the Long-term Phase (ITT Population). | The 30-item Inventory of Depressive Symptomatology (IDS-C/SR) (Rush et al. 1986, 1996) is designed to assess the severity of depressive symptoms. Scale range minimum = 0 / maximum = 84. Higher values are considered to be worse outcomes. The IDS-SR mean percent change at week 50 | From baseline to Study Week 50 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Chronic Depression, Bipolar Disorder