Microburst Vagus Nerve Stimulator (VNS) Therapy Feasibility Study (Microburst)

Microburst VNS Therapy Feasibility Study in Subjects With Refractory Epilepsy

Evaluate the initial safety and effectiveness of Microburst VNS stimulation in subjects with refractory epilepsy.

Study Overview

• Status: Completed
• Conditions: Epilepsies, Partial; Epilepsy, Tonic-Clonic
• Intervention / Treatment: Device: Microburst Stimulation

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium
    • Ghent University Hosptial
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Colorado
    • Denver, Colorado, United States, 80204
      • University of Denver Colorado
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • New York
    • Ithaca, New York, United States, 10065
      • Weil-Cornell Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Duke University
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinical diagnosis of medically refractory epilepsy with primary generalized tonic-clonic seizures (limited to 20 subjects) or partial onset seizures including complex partial seizures with or without secondary generalization (limited to 20 subjects).
2. Must be on adjunctive antiepileptic medications.
3. Willing and capable to undergo multiple evaluations with functional magnetic resonance imaging (fMRI), electroencephalogram (EEG) and electrocardiogram (ECG).

4(A) For subjects with partial onset seizures: An average of ≥ 3 countable seizures per month based on seizure diary during the 3 month baseline period and no seizure-free interval greater than 30 days during those 3 months.

4(B) For subjects with PGTCs: Have at least ≥ 3 countable seizures during the 3 month baseline period. Note: Each seizure within a cluster may be counted as separate seizures.

5. 12 years of age or older.

6. Subject is a male or non-pregnant female adequately protected from conception. Females of childbearing potential must use an acceptable method of birth control.

7. Provide written informed consent-assent/Health Insurance Portability and Accountability Act (HIPAA) authorization and self-reported measures with minimal assistance as determined by the investigator.

Exclusion Criteria:

1. Currently using, or are expected to use, short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy.
2. A VNS Therapy System implant would (in the investigator's judgment) pose an unacceptable surgical or medical risk for the subject.
3. A planned procedure that is contraindicated for VNS therapy.
4. History of implantation of the VNS Therapy System.
5. Currently receiving treatment from an active implantable medical device.
6. Presence of contraindications to MRI per the MRI subject screening record.
7. Known clinically meaningful cardiovascular arrhythmias currently being managed by devices or treatments that interfere with normal intrinsic heart rate responses (e.g., pacemaker dependency, implantable defibrillator, beta adrenergic blocker medications).
8. History of chronotropic incompetence (commonly seen in subjects with sustained bradycardia [heart rate < 50 bpm]).
9. Cognitive or psychiatric deficit that in the investigator's judgment would interfere with the subject's ability to accurately complete study assessments.
10. History of status epilepticus within 1 year of study enrollment.
11. Dependent on alcohol or narcotic drugs as defined by DSM IV-TR within the past 2 years, based on history. Tests for drug or alcohol use will not be administered.
12. Currently being treated with prescribed medication that contains cannabis or cannabis related substance including recreational use.
13. Any history of psychogenic non-epileptic seizures.
14. Currently participating in another clinical study without LivaNova written approval.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Microburst Stimulation; Microburst stimulation to tolerability and effectiveness	Device: Microburst Stimulation; Implantable generator with new stimulation feature under study to determine the safety and effectiveness of device stimulation on different seizure types.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Primary Endpoint: Percent change from baseline in seizure frequency	For the primary endpoint, the change in the seizure frequency per month compared to baseline will be evaluated for each subject at follow-up visits month 6 and 12.	Up to 12 months study visit
Safety Primary Endpoint: Occurrence of stimulation related Adverse Events	Assess stimulation/device related adverse events at follow-up visits month 6 and 12.	Up to 12 months study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in seizure frequency per month based on seizure diary provided by the sponsor		Up to 12 months study visit
Change from baseline in seizure severity	As measured by the Seizure Severity Questionnaire (SSQ) scale (Cramer, 2002).	Up to 12 months study visit
Change from baseline in quality of life	As measured by the QOLIE-31-P for adults 18 years and older (Cramer et al.; 1998) and QOLIE-AD-48 for adolescents 12 to 17 years (Cramer et al.; 1999).	Up to 12 months study visit
Change from baseline in antiepileptic drug (AED) load	Estimated as the sum of the prescribed daily dose (PDD)/defined daily dose (DDD) ratios for each AED included in the treatment regimen (Deckers et al., 1997), where DDD (WHO ATC/DDD index) corresponds to the assumed average therapeutic daily dose of a drug used for its main indication.	Up to 12 months study visit
Suicidality as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)		Up to 12 months study visit
All adverse events		Up to 12 months visit

Collaborators and Investigators

• Sponsor: LivaNova
• Investigators: Principal Investigator: Selim Benbadis, MD, University of South Florida Health

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Actual): July 30, 2021
• Study Completion (Actual): October 27, 2021

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (Actual): February 27, 2018

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 21, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Epilepsy, Generalized; Epilepsy, Tonic-Clonic
• Other Study ID Numbers: LNN001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes