ASCEND: Vagus Nerve Stimulation Titration Protocol to Improve Tolerance and Accelerate Adaptation
Study Details
Study Description
Brief Summary
Post-market, on-label, double-blind, randomized, prospective, interventional, tolerability and clinical outcomes study to determine the number of patients achieving their final assigned VNS Therapy dose settings in patients with drug-resistant epilepsy who are being treated with adjunctive VNS Therapy using new titration protocols.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Post-market, on-label, double-blind, randomized, prospective, interventional, tolerability and clinical outcomes study is designed to determine which VNS Therapy titration paradigm allows more patients to achieve a therapeutic dose within a specified time frame. Additionally, the study will collect data on the acute tolerability and clinical outcomes for patients with drug-resistant epilepsy treated with adjunctive VNS Therapy employing three different titration paradigms.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Group A Vagus Nerve Stimulation Therapy Standard Titration |
Device: Vagus Nerve Stimulation Therapy
Stimulation of the left tenth cranial nerve via VNS Therapy
Other Names:
|
| Group B Vagus Nerve Stimulation Therapy Alternate Titration 1 |
Device: Vagus Nerve Stimulation Therapy
Stimulation of the left tenth cranial nerve via VNS Therapy
Other Names:
|
| Group C Vagus Nerve Stimulation Therapy Alternate Titration 2 |
Device: Vagus Nerve Stimulation Therapy
Stimulation of the left tenth cranial nerve via VNS Therapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percent Patients Reaching the Defined Target Dose [12 weeks post implant]
Determination of the proportion (percent) of patients in each VNS Therapy titration group reaching the defined target dose within clinically defined titration time-frame
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must agree to be treated with VNS Therapy. The decision to treat with VNS Therapy must have been made independent of and prior to participation in the study.
-
Patients must be 12 years or older and have partial onset seizures or must follow the indication for use statement for VNS Therapy.
-
Patient and/or caregiver must be able and willing to give accurate side effect reports, global impressions data and complete study instruments with minimal assistance throughout the study.
-
Patient or legal guardian understands study procedures and voluntarily signs an informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional policies. In the event the patient is under the age of 18, the patient will also be required to sign an assent affirming agreement to participate in research according to local IRB requirements.
-
Patient must be taking at least 1 anti-epileptic drug treatment
Exclusion Criteria:
-
Patient currently uses, or is expected to use during the study, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy.
-
Patient is expected to require MRI using a body coil for transmission of RF during the clinical study.
-
Patient has a progressive neurological condition (e.g. brain tumor etc.).
-
In the investigator's opinion, the patient or legal guardian is unable to comply with the frequency of clinic visits during the study.
-
Patient is currently using an investigational device or pharmacologic medication not approved by the FDA.
-
Patient was previously implanted with VNS Therapy.
-
In the investigator's opinion, the patient is considered a suicide risk or is otherwise not a good candidate for this study.
-
Patient/Caregiver is unable to complete the required study follow-up visits and assessments.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Barrow Neurological Institute | Phoenix | Arizona | United States | 85013 |
| 2 | Loma Linda University | Loma Linda | California | United States | 92354 |
| 3 | University of Southern California | Los Angeles | California | United States | 90033 |
| 4 | Tampa General Hospital | Tampa | Florida | United States | 33606 |
| 5 | Emory University | Atlanta | Georgia | United States | 30329 |
| 6 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 7 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 8 | St. Joseph's Hospital | Lexington | Kentucky | United States | 40504 |
| 9 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 10 | Mercy Medical Research Institue | Springfield | Missouri | United States | 65804 |
| 11 | University of Nebraska | Omaha | Nebraska | United States | 68131 |
| 12 | University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15213 |
| 13 | Covenant Hospital | Lubbock | Texas | United States | 79410 |
| 14 | Scott & White Healthcare | Temple | Texas | United States | 76508 |
| 15 | University of Utah | Salt Lake City | Utah | United States | 84132 |
Sponsors and Collaborators
- Cyberonics, Inc.
Investigators
- Study Director: Jeff Way, Cyberonics, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E-40
Study Results
Participant Flow
| Recruitment Details | Subjects enrolled at 15 clinical sites including university and private hospital clinics. Enrollment was allowed following successful initiation of the first clinical site on 04MAR2015 and closed on 29JUN2016. The first subject enrolled on 28APR2015 and the final two subjects enrolled on 29JUN2016. The final subject exited the study on 10OCT2016. |
|---|---|
| Pre-assignment Detail | All subjects were required to receive implantation of a commercially available Vagus Nerve Stimulation generator (Stimulation of the left tenth cranial nerve via VNS Therapy) prior to randomization. The generator was to remain "off" until after randomization completion. |
| Arm/Group Title | Group A | Group B | Group C |
|---|---|---|---|
| Arm/Group Description | Vagus Nerve Stimulation Therapy Standard Titration method | Vagus Nerve Stimulation Therapy Alternate Titration 1 Alternate titration method that combined methods from Group A and Group C. | Vagus Nerve Stimulation Therapy Alternate Titration 2 Alternate titration method used in the ANTHEM-HF trial which evaluated the performance of autonomic regulation using VNS Therapy in patients with chronic symptomatic heart failure and reduced ejection fraction. |
| Period Title: Overall Study | |||
| STARTED | 22 | 20 | 20 |
| COMPLETED | 20 | 17 | 20 |
| NOT COMPLETED | 2 | 3 | 0 |
Baseline Characteristics
| Arm/Group Title | Group A | Group B | Group C | Total |
|---|---|---|---|---|
| Arm/Group Description | Vagus Nerve Stimulation Therapy Standard Titration method | Vagus Nerve Stimulation Therapy Alternate Titration 1 Alternate titration method that combined methods from Group A and Group C. | Vagus Nerve Stimulation Therapy Alternate Titration 2 Alternate titration method used in the ANTHEM-HF trial which evaluated the performance of autonomic regulation using VNS Therapy in patients with chronic symptomatic heart failure and reduced ejection fraction. | Total of all reporting groups |
| Overall Participants | 22 | 20 | 20 | 62 |
| Age (Count of Participants) | ||||
| <=18 years |
1
4.5%
|
0
0%
|
0
0%
|
1
1.6%
|
| Between 18 and 65 years |
21
95.5%
|
19
95%
|
19
95%
|
59
95.2%
|
| >=65 years |
0
0%
|
1
5%
|
1
5%
|
2
3.2%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
16
72.7%
|
11
55%
|
10
50%
|
37
59.7%
|
| Male |
6
27.3%
|
9
45%
|
10
50%
|
25
40.3%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White Non-Hispanic |
15
68.2%
|
17
85%
|
13
65%
|
45
72.6%
|
| Black or African American |
3
13.6%
|
1
5%
|
1
5%
|
5
8.1%
|
| Hispanic or Latino |
4
18.2%
|
2
10%
|
6
30%
|
12
19.4%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
22
100%
|
20
100%
|
20
100%
|
62
100%
|
Outcome Measures
| Title | Percent Patients Reaching the Defined Target Dose |
|---|---|
| Description | Determination of the proportion (percent) of patients in each VNS Therapy titration group reaching the defined target dose within clinically defined titration time-frame |
| Time Frame | 12 weeks post implant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population of subjects implanted with Vagus Nerve Therapy generator who received stimulation via left, tenth cranial nerve at varying dosing methods (device settings adjustments) depending on the group each subject was randomized. All subject had a common, final target dose to achieve but used alternate methods to achieve the target dose. |
| Arm/Group Title | Group A | Group B | Group C |
|---|---|---|---|
| Arm/Group Description | Vagus Nerve Stimulation Therapy Standard Titration method | Vagus Nerve Stimulation Therapy Alternate Titration 1 Alternate titration method that combined methods from Group A and Group C. | Vagus Nerve Stimulation Therapy Alternate Titration 2 Alternate titration method used in the ANTHEM-HF trial which evaluated the performance of autonomic regulation using VNS Therapy in patients with chronic symptomatic heart failure and reduced ejection fraction. |
| Measure Participants | 22 | 20 | 20 |
| Count of Participants [Participants] |
18
81.8%
|
9
45%
|
12
60%
|
Adverse Events
| Time Frame | Adverse event data was collected for the duration of each subjects study participation of 12 weeks. This period began from the first enrollment 28APR2015 to the final exit 10OCT2016. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse reporting occurred via subject reporting and investigator assessment during the scheduled subject visits. Events related to epilepsy were not to be recorded unless a worsening from baseline was observed or experienced. | |||||
| Arm/Group Title | Group A | Group B | Group C | |||
| Arm/Group Description | Vagus Nerve Stimulation Therapy Standard Titration method | Vagus Nerve Stimulation Therapy Alternate Titration 1 Alternate titration method that combined methods from Group A and Group C. | Vagus Nerve Stimulation Therapy Alternate Titration 2 Alternate titration method used in the ANTHEM-HF trial which evaluated the performance of autonomic regulation using VNS Therapy in patients with chronic symptomatic heart failure and reduced ejection fraction. | |||
All Cause Mortality |
||||||
| Group A | Group B | Group C | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/22 (0%) | 0/20 (0%) | 0/20 (0%) | |||
Serious Adverse Events |
||||||
| Group A | Group B | Group C | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/22 (0%) | 0/20 (0%) | 1/20 (5%) | |||
| Vascular disorders | ||||||
| Peripheral arterial occlusive disease | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Group A | Group B | Group C | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/22 (40.9%) | 7/20 (35%) | 9/20 (45%) | |||
| Cardiac disorders | ||||||
| Palpatations [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Cerumen impaction [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Tinnitus [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Gastrointestinal disorders | ||||||
| Constipation [U] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Diarrhoea [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 3/20 (15%) | 3 |
| Dysphagia [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| General disorders | ||||||
| Chest Pain [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Discomfort [S] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Fatigue [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Implant site hoematoma [I] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Medical device discomfort [S] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Medical device pain [S] [SI] | 1/22 (4.5%) | 1 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Non-cardiac chest pain [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Infections and infestations | ||||||
| Cellulitis [U] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Lower respiratory tract infection [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Nasopharyngitis [U] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Staphyloccal infection [I] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Urinary tract infection [U] | 0/22 (0%) | 0 | 2/20 (10%) | 2 | 0/20 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Incision site haematoma [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Incision site hypoaesthesia [I] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Incision site pain [I] | 0/22 (0%) | 0 | 3/20 (15%) | 4 | 0/20 (0%) | 0 |
| Post procedural haemorrhage [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Procedural headache [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 1/20 (5%) | 1 |
| Procedural nausea [U] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Back pain [U] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Muscle spasms [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Muscle tightness [SI] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Muscle twitching [S] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Myalgia [I] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Neck pain [I] | 2/22 (9.1%) | 2 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Pain in extremety [I] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Pain in jaw [U] [S] | 1/22 (4.5%) | 1 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Nervous system disorders | ||||||
| Convulsion [U] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 1/20 (5%) | 1 |
| Headache [U] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Migraine [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Paraesthesia [S] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Postural tremor [S] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Somnolence [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 2/20 (10%) | 2 |
| Psychiatric disorders | ||||||
| Anxiety [U] [SI] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma [U] | 1/22 (4.5%) | 1 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Cough [S] | 2/22 (9.1%) | 2 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Dysphonia [S] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Oropharyngeal pain [I] [S] | 1/22 (4.5%) | 2 | 2/20 (10%) | 2 | 0/20 (0%) | 0 |
| Sleep apnoea syndrome [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Sputum increased [SI] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 1 |
| Throat tightness [S] | 2/22 (9.1%) | 2 | 0/20 (0%) | 0 | 0/20 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Pruritis [S] | 0/22 (0%) | 0 | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Vascular disorders | ||||||
| Peripheral arterial occlusive disease [U] | 0/22 (0%) | 0 | 0/20 (0%) | 0 | 1/20 (5%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Peter Sears, Clinical Project Manager |
|---|---|
| Organization | Cyberonics, Inc. |
| Phone | (281) 228-7597 |
| peter.sears@cyberonics.com |
- E-40