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

• ClinicalTrials.gov Identifier: NCT03446664
• Recruitment Status: Active, not recruiting
• First Posted: February 27, 2018
• Last Update Posted: December 16, 2020
• Sponsor: LivaNova
• Information provided by (Responsible Party): LivaNova

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Epilepsies, Partial; Epilepsy, Tonic-Clonic	Device: Microburst Stimulation	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Two cohorts of subjects with refractory epilepsy; (1) subjects with primary generalized tonic-clonic seizures and (2) subjects with partial onset seizures including complex partial seizures with or without secondary generalization.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Microburst VNS Therapy Feasibility Study in Subjects With Refractory Epilepsy
• Actual Study Start Date: February 27, 2018
• Estimated Primary Completion Date: September 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Efficacy Primary Endpoint: Percent change from baseline in seizure frequency [ Time Frame: Up to 12 months study visit ]
   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.
2. Safety Primary Endpoint: Occurrence of stimulation related Adverse Events [ Time Frame: Up to 12 months study visit ]
   Assess stimulation/device related adverse events at follow-up visits month 6 and 12.

Secondary Outcome Measures :

1. Change from baseline in seizure frequency per month based on seizure diary provided by the sponsor [ Time Frame: Up to 12 months study visit ]
2. Change from baseline in seizure severity [ Time Frame: Up to 12 months study visit ]
   As measured by the Seizure Severity Questionnaire (SSQ) scale (Cramer, 2002).
3. Change from baseline in quality of life [ Time Frame: Up to 12 months study visit ]
   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).
4. Change from baseline in antiepileptic drug (AED) load [ Time Frame: Up to 12 months study visit ]
   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.
5. Suicidality as measured by the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to 12 months study visit ]
6. All adverse events [ Time Frame: Up to 12 months visit ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, Colorado

University of Denver Colorado

Denver, Colorado, United States, 80204

United States, Florida

Mayo Clinic Florida

Jacksonville, Florida, United States, 32224

United States, Illinois

Rush University

Chicago, Illinois, United States, 60612

Northwestern University

Evanston, Illinois, United States, 60208

United States, New York

Weil-Cornell Medical College

Ithaca, New York, United States, 10065

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27708

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84112

Belgium

Ghent University Hosptial

Ghent, Belgium

Sponsors and Collaborators

LivaNova

Investigators

• Principal Investigator: Selim Benbadis, MD; University of South Florida Health

More Information

• Responsible Party: LivaNova
• ClinicalTrials.gov Identifier: NCT03446664
• Other Study ID Numbers: LNN001
• First Posted: February 27, 2018
• Last Update Posted: December 16, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Additional relevant MeSH terms:

Epilepsy; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Epilepsy, Generalized; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases