Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures

NCT01118455 | Terminated Phase 4 Results

• 1 other identifier: Epilepsy (E)-06
• Study Type: interventional
• Target: 134
• Locations: 5 countries
• Sites: 19

Brief Summary

This is a randomized study designed to compare long-term treatment outcomes in pediatric patients with refractory seizures treated with VNS (Vagus Nerve Stimulation) Therapy versus anti-epileptic drugs (AEDs). Seizure reduction, quality of life measures, and side effect profiles will be evaluated. The results of this study will provide controlled comparative data to better guide physicians in determining the best overall treatment strategy for patients with seizures who have failed initial AED therapy.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (1)

• Proportion of Responders After 1 Year of Follow-up (ITT-population)

  Responders are subjects who had no new AEDs added or significant dose changes in baseline AEDs within 1 year of follow-up, along with a reduction in the percentage change in seizure frequency from baseline to the 2-month period prior to the 1-year follow-up of at least 50%.

  52 weeks post baseline

Secondary Outcomes (6)

• Mean Percent Change in Hague Seizure Severity Scale Score (ITT Population)

  52 weeks post baseline

• Wellcome Quality of Life Assessment (Questionnaire A) in Epilepsy (ITT Population)

  52 weeks post baseline

• Hague Restriction in Childhood Epilepsy Scale (Questionnaire B) (ITT Population)

  52 weeks post baseline

• Mean Percent Change in Seizure Frequency (ITT Population)

  52 weeks post baseline

• Number of Subjects With Any Non-Serious Adverse Events by System Organ Class and Preferred Term (Safety Population)

  0-52 weeks

Study Arms (2)

Vagus Nerve Stimulation (VNS) Therapy

EXPERIMENTAL

Vagus Nerve Stimulation (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.

Device: Vagus Nerve Stimulation (VNS) Therapy

Anti-Epileptic Drug (AED)

EXPERIMENTAL

This arm will supply a comparison between VNS and new AEDs which is necessary to determine an overall treatment regimen for the 30% to 40% of patients who fail to respond to 2 AEDs.

Drug: Anti-Epileptic Drug (AED)

Interventions

Vagus Nerve Stimulation (VNS) Therapy DEVICE

Vagus Nerve Stimulation (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.

Vagus Nerve Stimulation (VNS) Therapy

Anti-Epileptic Drug (AED) DRUG

Subject has tried at least 2 appropriate AEDs tested to tolerance or to blood levels at upper end of the target range of which at least 2 had been tolerated at normal doses.

Anti-Epileptic Drug (AED)

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Refractory seizures
• Having tried at least two appropriate anti-epileptic drugs (AEDs) tested to tolerance or to blood levels at upper end of the target range of which at least 2 have been tolerated at normal dose;
• Having at least 3 appropriate AEDs left to try
• Having his/her current AED medication at an optimal dose at baseline
• At least three seizures per month (average over 2 months prior to admission), excluding absences.
• No more than four (4) weeks between seizures (over 2 months prior to admission)
• Age 17 years or less
• Having been evaluated for epilepsy surgery and resective surgery not felt indicated or patient/parents/legal guardian declined.
• Patient is a male or patient is a nonpregnant female adequately protected from conception. Females of childbearing potential must use an acceptable method of birth control. Abstinence is an acceptable means of birth control
• Patient or legal guardian understands study procedures and has voluntarily signed an informed consent in accordance with institutional policies.

You may not qualify if:

• Having tried less then 2 AEDs tested to tolerance or to blood levels at upper end of the target range of which at least 2 have been tolerated at normal doses in the patient's lifetime
• A progressive neurological condition (e.g. brain tumor etc.)
• Inability of the parents or reluctance of the child to comply with the frequency of clinic visits during the treatment phase
• Patient has a history of noncompliance for seizure diary completion.
• Patient has taken an investigational drug within a period of five times the mean elimination half-life of the investigational drug plus two weeks.
• Patient is currently using another investigational device or drug.
• Patient is likely to require a whole body Magnetic resonance imaging (MRI) after VNS Therapy device implantation. (Refer to the Physician's Manual for the NCP Generator for additional information on the use of MRI.)
• Patient is currently receiving or likely to receive short-wave diathermy, microwave diathermy, or therapeutic ultrasound diathermy after implantation (Refer to Physician's Manual for the VNS (Vagus Nerve Stimulation) Therapy device for additional information on the contraindicated use of diathermy).
• Patient was previously enrolled in this or any other VNS Therapy device Study.
• Patient has an active peptic ulcer
• Patient has another unstable medical condition likely to precipitate seizures and make it difficult to evaluate to evaluate efficacy (e.g. diabetes)
• Patient has had a unilateral or bilateral cervical vagotomy.
• Patient is pregnant at the time of enrolment.

Sponsors & Collaborators

• Cyberonics, Inc.: lead

Study Sites (19)

Medical University of Vienna - Vienna General Hospital (AKH)

Vienna, Austria

Location

ULB- Hospital Erasme

Brussels, Belgium

Location

Kinderklinik der Justus-Liebig Universität

Giessen, Germany

Location

University Children's Hospital

Lübeck, Germany

Location

University Hospital Lund

Lund, Sweden

Location

Astrid Lindgrens Barnsjukhus Karolinska

Stockholm, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Birmingham Children's Hospital

Birmingham, United Kingdom

Location

Royal Hospital for Sick Children

Bristol, United Kingdom

Location

Addenbrookes Hospital

Cambridge, United Kingdom

Location

Ninewells Hospital & Medical School

Dundee, United Kingdom

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

Great Ormond Street Hospital for Children

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, United Kingdom

Location

Sir James Spence Institute - Royal Victoria Infirmary

Newcastle, United Kingdom

Location

Queens's Medical Centre Nottingham

Nottingham, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, United Kingdom

Location

Southampton Hospital

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Epilepsy

Interventions

Vagus Nerve Stimulation; Therapeutics; Anticonvulsants

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Limitations and Caveats

Study was terminated due to low enrollment.

Results Point of Contact

• Title: Mark Bunker, PharmD, Sr. Director, Global Medical Affairs
• Organization: Cyberonics, Inc.

Mark.Bunker@cyberonics.com

281-228-7223

Study Officials

• Mark Bunker, PharmD

  Cyberonics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: May 6, 2010
• Study Start: October 1, 2004
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2010
• Last Updated: June 26, 2014
• Results First Posted: June 26, 2014

Record last verified: 2014-06

Locations

SE (3); GB (12); BE (1); DE (2); AU (1)