Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients

This study has been terminated.

(Insufficient enrollment)

Sponsor:

Information provided by (Responsible Party):

Cyberonics, Inc.

ClinicalTrials.gov Identifier:

NCT00522418

First received: August 27, 2007

Last updated: October 22, 2012

Last verified: October 2012

History of Changes

Results First Received: April 2, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Epilepsy Partial Epilepsy
Interventions:	Device: Vagal Nerve Simulation (VNS) Therapy Drug: Best Medical Practive

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was started in February 2006 at 41 sites and terminated on July 28, 2008 as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients were randomized in a 1:1 ratio to the Best Medical Practice With Adjunctive VNS Therapy study group or to the Best Medical Practice Without VNS Therapy study group. VNS Therapy is delivered by an implantable device similar to a pacemaker that sends mild stimulation to the left vagus nerve to help improve seizure control.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Participant Flow: Overall Study

	VNS Therapy	Best Medical Practice
STARTED	59	63
COMPLETED	2	4
NOT COMPLETED	57	59
Consent Withdraw	1	2
Treatment Failure	0	1
Subject Nonadherence	3	2
Protocol Nonadherence	4	5
Study Termination	47	48
Not Specified	1	1
Lack of Baseline data	1	0

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy
Total	Total of all reporting groups

Baseline Measures

	VNS Therapy	Best Medical Practice	Total
Number of Participants [units: participants]	59	63	122
Age ^[1] [units: Years] Mean ± Standard Deviation	38.1 ± 11.9	41.3 ± 11.5	39.7 ± 11.8
Gender [units: participants]
Female	29	28	57
Male	30	35	65
Epilepsy Etiology [units: participants]
Idiopathic	0	0	0
Symptomatic	30	31	61
Cryptogenic	29	32	61
Simple Partial Seizures ^[2] [units: patients]
No	38	34	72
Yes	17	28	45
Unknown	4	1	5
Age of Epilepsy Onset ^[3] [units: years] Mean ± Standard Deviation	12.5 ± 12.5	15.5 ± 12.5	14.0 ± 12.6
Blood Pressure - Diastolic ^[4] [units: Millimeters of mercury (mmHg)] Mean ± Standard Deviation	77.1 ± 8.0	78.4 ± 8.6	77.8 ± 8.3
Blood Pressure - Systolic ^[4] [units: Millimeters of mercury (mmHg)] Mean ± Standard Deviation	125.2 ± 12.6	125.5 ± 11.7	125.3 ± 12.1
Heart Rate ^[3] [units: Beats per minute] Mean ± Standard Deviation	74.9 ± 7.8	73.0 ± 6.5	73.9 ± 7.2
Height ^[5] [units: centimeters (cm)] Mean ± Standard Deviation	169.7 ± 9.1	171.4 ± 10.9	170.6 ± 10.1
Weight ^[5] [units: kilogram (kg)] Mean ± Standard Deviation	72.4 ± 14.5	76.0 ± 19.4	74.3 ± 17.2

[1]	Age at Randomization
[2]	Data available for 55/59 of VNS Therapy Group and 62/63 of Best Medical Practice Group.
[3]	Data available for 58/59 of VNS Therapy Group and 61/63 of Best Medical Practice Group.
[4]	Data available for 59/59 of VNS Therapy Group and 61/63 of Best Medical Practice Group.
[5]	Data available for 59/59 of VNS Therapy Group and 62/63 of Best Medical Practice Group.

Outcome Measures

Hide All Outcome Measures

1. Primary:

Quality of Life in Epilepsy (QOLIE-89) [ Time Frame: Mean score at 21 and 24 months ]

Measure Type	Primary
Measure Title	Quality of Life in Epilepsy (QOLIE-89)
Measure Description	QOLIE-89 contains 17 multi-item measures of overall quality of life, emotional well-being, role limitations due to emotional problems, social support, social isolation, energy/fatigue, worry about seizure, medication effects, health discouragement, work/driving/social function, attention/concentration, language, memory, physical function, pain, role limitations due to physical problems, and health perceptions. Range of values 0-100. Higher scores reflect better quality of life; lower ones, worse quality of life.
Time Frame	Mean score at 21 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Quality of Life in Epilepsy (QOLIE-89)

No statistical analysis provided for Quality of Life in Epilepsy (QOLIE-89)

2. Secondary:

Response Rate [ Time Frame: 3, 6 , 9, 12, 15, 18, 21, and 24 months ]

Measure Type	Secondary
Measure Title	Response Rate
Measure Description	Response Rate is defined as the percent of participants who are responders. A Responder is defined as participants with a reduction of at least 50% or 75% in seizure frequency from baseline to the seizure count evaluation period.
Time Frame	3, 6 , 9, 12, 15, 18, 21, and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Response Rate

No statistical analysis provided for Response Rate

3. Secondary:

Percent of Patients That Are Seizure Free [ Time Frame: 3, 6, 9, 12, 15, 18, 21, 24 months ]

Measure Type	Secondary
Measure Title	Percent of Patients That Are Seizure Free
Measure Description	Percent of patients that are seizure free as defined by no seizures during the preceding follow-up period.
Time Frame	3, 6, 9, 12, 15, 18, 21, 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Percent of Patients That Are Seizure Free

No statistical analysis provided for Percent of Patients That Are Seizure Free

4. Secondary:

Mean Percent Change in Seizure Frequency [ Time Frame: 3, 6, 9, 12, 15, 18, 21, 24 months ]

Measure Type	Secondary
Measure Title	Mean Percent Change in Seizure Frequency
Measure Description	Mean percent change in seizure frequency compared to baseline value.
Time Frame	3, 6, 9, 12, 15, 18, 21, 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Mean Percent Change in Seizure Frequency

No statistical analysis provided for Mean Percent Change in Seizure Frequency

5. Secondary:

Seizure Free Days [ Time Frame: From the patient's last seizure to the study exit date ]

Measure Type	Secondary
Measure Title	Seizure Free Days
Measure Description	Seizure free days is defined as the time from last seizure to study exit date.
Time Frame	From the patient's last seizure to the study exit date
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Seizure Free Days

No statistical analysis provided for Seizure Free Days

6. Secondary:

Seizure Free Days Over the Last 6 Months [ Time Frame: Over the last 6 months ]

Measure Type	Secondary
Measure Title	Seizure Free Days Over the Last 6 Months
Measure Description	No text entered.
Time Frame	Over the last 6 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Seizure Free Days Over the Last 6 Months

No statistical analysis provided for Seizure Free Days Over the Last 6 Months

7. Secondary:

Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Center for Epidemiologic Studies Depression Scale (CES-D)
Measure Description	The Center for Epidemiologic Studies Depression Scale (CES-D) includes 20 items comprising six scales reflecting major dimensions of depression: depressed mood, feelings of guilt and worthlessness, feelings of helplessness and hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance. Possible range of scores is 0 to 60, higher scores indicate more depressive symptoms.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Center for Epidemiologic Studies Depression Scale (CES-D)

No statistical analysis provided for Center for Epidemiologic Studies Depression Scale (CES-D)

8. Secondary:

Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)
Measure Description	The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in people with epilepsy. Scores range from 6 to 24, with higher scores indicating more depressive symptoms.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)

No statistical analysis provided for Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)

9. Secondary:

Clinical Global Impressions Scale (CGI) [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Clinical Global Impressions Scale (CGI)
Measure Description	The Clinical Global Impression scale (CGI-I)is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention Scores range from 1-7: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Clinical Global Impressions Scale (CGI)

No statistical analysis provided for Clinical Global Impressions Scale (CGI)

10. Secondary:

Adverse Event Profile (AEP) [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Adverse Event Profile (AEP)
Measure Description	Adverse Events Profile (AEP) is a 19-item scale used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). Scores range from 19-76; higher scores indicate high prevelance and severity of adverse events.
Time Frame	At 12 and 24 months
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Adverse Event Profile (AEP)

No statistical analysis provided for Adverse Event Profile (AEP)

11. Secondary:

Changes in Anti-epileptic Drugs (AEDs) [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Changes in Anti-epileptic Drugs (AEDs)
Measure Description	Change in the number of anti-epileptic drugs perscribed.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Changes in Anti-epileptic Drugs (AEDs)

No statistical analysis provided for Changes in Anti-epileptic Drugs (AEDs)

12. Secondary:

Retention Rate [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Retention Rate
Measure Description	Percent of participants who were compliant with the protocol.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Retention Rate

No statistical analysis provided for Retention Rate

13. Secondary:

Treatment Emergent Adverse Events, Device Complications, and Premature Study Withdrawal [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Treatment Emergent Adverse Events, Device Complications, and Premature Study Withdrawal
Measure Description	Number of participants with treatment emergent adverse events, device complications, and premature Study withdrawal.
Time Frame	At 12 and 24 months
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Treatment Emergent Adverse Events, Device Complications, and Premature Study Withdrawal

No statistical analysis provided for Treatment Emergent Adverse Events, Device Complications, and Premature Study Withdrawal

14. Secondary:

Quality of Life in Epilepsy - 89 Items(QOLIE-89)in Patients With Less Than a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Quality of Life in Epilepsy - 89 Items(QOLIE-89)in Patients With Less Than a 50% Reduction in Seizures
Measure Description	QOLIE-89 contains 17 multi-item measures of overall quality of life, emotional well-being, role limitations due to emotional problems, social support, social isolation, energy/fatigue, worry about seizure, medication effects, health discouragement, work/driving/social function, attention/concentration, language, memory, physical function, pain, role limitations due to physical problems, and health perceptions. Range of values 0-100. Higher scores reflect better quality of life; lower ones, worse quality of life.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Quality of Life in Epilepsy - 89 Items(QOLIE-89)in Patients With Less Than a 50% Reduction in Seizures

No statistical analysis provided for Quality of Life in Epilepsy - 89 Items(QOLIE-89)in Patients With Less Than a 50% Reduction in Seizures

15. Secondary:

Centre for Epidemiologic Studies Depression Scale (CES-D) in Patients With Less Then a 50% Reduction [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Centre for Epidemiologic Studies Depression Scale (CES-D) in Patients With Less Then a 50% Reduction
Measure Description	The Center for Epidemiologic Studies Depression Scale (CES-D) includes 20 items comprising six scales reflecting major dimensions of depression: depressed mood, feelings of guilt and worthlessness, feelings of helplessness and hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance. Possible range of scores is 0 to 60, higher scores indicate more depressive symptoms.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Centre for Epidemiologic Studies Depression Scale (CES-D) in Patients With Less Then a 50% Reduction

No statistical analysis provided for Centre for Epidemiologic Studies Depression Scale (CES-D) in Patients With Less Then a 50% Reduction

16. Secondary:

Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in Patients With Less Then a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in Patients With Less Then a 50% Reduction in Seizures
Measure Description	The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is a 6-item questionnaire validated to screen for depression in people with epilepsy. Scores range from 6 to 24, with higher scores indicating more depressive symptoms.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in Patients With Less Then a 50% Reduction in Seizures

No statistical analysis provided for Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in Patients With Less Then a 50% Reduction in Seizures

17. Secondary:

Adverse Event Profile (AEP) in Patients With Less Then a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Adverse Event Profile (AEP) in Patients With Less Then a 50% Reduction in Seizures
Measure Description	Adverse Events Profile (AEP) is a 19-item scale used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). Scores range from 19-76; higher scores indicate high prevelance and severity of adverse events.
Time Frame	At 12 and 24 months
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Adverse Event Profile (AEP) in Patients With Less Then a 50% Reduction in Seizures

No statistical analysis provided for Adverse Event Profile (AEP) in Patients With Less Then a 50% Reduction in Seizures

18. Secondary:

Change in the Number of Anti-epileptic Drugs Prescribed [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Change in the Number of Anti-epileptic Drugs Prescribed
Measure Description	Changes in Anti-Epileptic Drugs (AEDs) in patients with less then a 50% reduction in seizures
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Change in the Number of Anti-epileptic Drugs Prescribed

No statistical analysis provided for Change in the Number of Anti-epileptic Drugs Prescribed

19. Secondary:

Percent of Participants Who Were Compliant With the Protocol [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Percent of Participants Who Were Compliant With the Protocol
Measure Description	Retention rate in patients with less then a 50% reduction in seizures
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Percent of Participants Who Were Compliant With the Protocol

No statistical analysis provided for Percent of Participants Who Were Compliant With the Protocol

20. Secondary:

Quality of Life in Epilepsy-89 (QOLIE-89) in Patients With a Baseline AEP Score Less Than 40 Versus Those Patients With a Baseline AEP Score Greater Than or Equal to 40 [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Quality of Life in Epilepsy-89 (QOLIE-89) in Patients With a Baseline AEP Score Less Than 40 Versus Those Patients With a Baseline AEP Score Greater Than or Equal to 40
Measure Description	QOLIE-89 contains 17 multi-item measures of overall quality of life. Range of values 0-100. Higher scores reflect better quality of life; lower ones, worse quality of life. Adverse Events Profile (AEP) is a 19-item scale used as a systematic measure of adverse effects from antiepileptic drugs (AEDs). Scores range from 19-76; higher scores indicate high prevelance and severity of adverse events.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Quality of Life in Epilepsy-89 (QOLIE-89) in Patients With a Baseline AEP Score Less Than 40 Versus Those Patients With a Baseline AEP Score Greater Than or Equal to 40

No statistical analysis provided for Quality of Life in Epilepsy-89 (QOLIE-89) in Patients With a Baseline AEP Score Less Than 40 Versus Those Patients With a Baseline AEP Score Greater Than or Equal to 40

21. Secondary:

Clinical Global Impressions Scale (CGI) in Patients With Less Then a 50% Reduction in Seizures [ Time Frame: At 12 and 24 months ]

Measure Type	Secondary
Measure Title	Clinical Global Impressions Scale (CGI) in Patients With Less Then a 50% Reduction in Seizures
Measure Description	The Clinical Global Impression scale (CGI-I)is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention Scores range from 1-7: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame	At 12 and 24 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This study was started in February 2006 at 41 sites and terminated on July 28, 2008, at 122 of 362 planned patients as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Reporting Groups

	Description
VNS Therapy	VNS Therapy + Best Medical Practice
Best Medical Practice	Best Medical Practice Without VNS Therapy

Measured Values

	VNS Therapy	Best Medical Practice
Number of Participants Analyzed [units: participants]	0	0
Clinical Global Impressions Scale (CGI) in Patients With Less Then a 50% Reduction in Seizures

No statistical analysis provided for Clinical Global Impressions Scale (CGI) in Patients With Less Then a 50% Reduction in Seizures

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Investigator and Site agree not to publish or otherwise publicaly disclose clinical data generated in connection with the Study, unless approved in advance in writing by Cyberonics. Investigators and Site agree to provide Cyberonics with a copy of any proposed publication, abstract, or presentation relating to the research conducted under this Agreement at least 30 days prior to submission for publication or presentation.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
This study was terminated as a result of a decision by Cyberonics, Inc. The decision to terminate the study was primarily due to insufficient enrollment. The decision was not the result of a safety or efficacy signal.

Results Point of Contact:

Name/Title: Senior Director, Global Medical Affairs
Organization: Cyberonics, Inc
phone: 281-228-7223
e-mail: Mark.Bunker@cyberonics.com

Publications:

Gilliam F. Optimizing health outcomes in active epilepsy. Neurology. 2002 Apr 23;58(8 Suppl 5):S9-20. Review.

Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000 Feb 3;342(5):314-9.

Sillanpaa M, Jalava M, Kaleva O, Shinnar S. Long-term prognosis of seizures with onset in childhood. N Engl J Med. 1998 Jun 11;338(24):1715-22.

Mattson RH, Cramer JA, Collins JF, Smith DB, Delgado-Escueta AV, Browne TR, Williamson PD, Treiman DM, McNamara JO, McCutchen CB, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med. 1985 Jul 18;313(3):145-51.

Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med. 1992 Sep 10;327(11):765-71.

Mattson RH, Cramer JA, Collins JF. Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group. Neurology. 1996 Jul;47(1):68-76.

Schmidt D. The clinical impact of new antiepileptic drugs after a decade of use in epilepsy. Epilepsy Res. 2002 Jun;50(1-2):21-32. Review.

Lhatoo SD, Wong IC, Polizzi G, Sander JW. Long-term retention rates of lamotrigine, gabapentin, and topiramate in chronic epilepsy. Epilepsia. 2000 Dec;41(12):1592-6.

Morris GL 3rd, Mueller WM. Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology. 1999 Nov 10;53(8):1731-5. Erratum in: Neurology 2000 Apr 25;54(8):1712.

Malow BA, Edwards J, Marzec M, Sagher O, Ross D, Fromes G. Vagus nerve stimulation reduces daytime sleepiness in epilepsy patients. Neurology. 2001 Sep 11;57(5):879-84.

Harden CL, Pulver MC, Ravdin LD, Nikolov B, Halper JP, Labar DR. A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation. Epilepsy Behav. 2000 Apr;1(2):93-99.

Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE. Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res. 2000 Dec;42(2-3):203-10.

Clark KB, Naritoku DK, Smith DC, Browning RA, Jensen RA. Enhanced recognition memory following vagus nerve stimulation in human subjects. Nat Neurosci. 1999 Jan;2(1):94-8.

McLachlan RS, Sadler M, Pillay N, Guberman A, Jones M, Wiebe S, Schneiderman J. Quality of life after vagus nerve stimulation for intractable epilepsy: is seizure control the only contributing factor? Eur Neurol. 2003;50(1):16-9.

Cramer JA, Ben Menachem E, French J. Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation. Epilepsy Res. 2001 Nov;47(1-2):17-25. Review.

Gilliam FG, Fessler AJ, Baker G, Vahle V, Carter J, Attarian H. Systematic screening allows reduction of adverse antiepileptic drug effects: a randomized trial. Neurology. 2004 Jan 13;62(1):23-7.

Responsible Party:	Cyberonics, Inc.
ClinicalTrials.gov Identifier:	NCT00522418 History of Changes
Other Study ID Numbers:	E-100
Study First Received:	August 27, 2007
Results First Received:	April 2, 2010
Last Updated:	October 22, 2012
Health Authority:	Belgium: Institutional Review Board Canada: Ethics Review Committee France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Ethics Commission Italy: Ethics Committee Netherlands: Medical Ethics Review Committee (METC) Norway:National Committee for Medical and Health Research Ethics Spain: Comité Ético de Investigación Clínica Sweden: Regional Ethical Review Board United Kingdom: Research Ethics Committee

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