EpilepsyPhase 2NCT01159431

External Trigeminal Nerve Stimulation for Epilepsy

A Phase 2 study testing Trigeminal Nerve Stimulation in people with Epilepsy and Seizure Disorders, run by Olive View-UCLA Education & Research Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Epilepsy, Seizure Disorders
What is being tested?: Trigeminal Nerve Stimulation
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 2 sitesUnited States
Study dates: Jan 2008to Jun 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Ages 18 - 70;
No serious or progressive medical illness;
A history of intractable partial seizures;
At least two complex partial or tonic clonic generalized seizures per month in the last two consecutive months;
MRI or EEG consistent with localization-related or partial epilepsy;
Exposure to at least two antiepileptic drugs at adequate doses;
Concurrent use of at least one antiepileptic drug at adequate doses;
No change in antiepileptic dose for at least 30 days before study enrollment

Who cannot join

History of non-epileptic seizures;
Inability to maintain accurate seizure calendars (self or caregiver);
Frequent use of benzodiazepines for clusters defined as greater than four times a month;
History of facial pain or trigeminal neuralgia;
Concurrent vagus nerve stimulation;
Pregnancy

Trial locations and contacts

2 sites in 1 country.

United States2 sites

USC Department of Neurology
Los Angeles, California, 90033
Olive View/UCLA Medical Center
Sylmar, California, 91342

Other trials in United States

About this study

Official title: Randomized Double Blind Study of External Trigeminal Nerve Stimulation for Intractable Epilepsy

This study investigates a new therapy for epilepsy called Trigeminal Nerve Stimulation (TNS). TNS involves external electrical stimulation of sensory nerve located above the eyes and over the forehead. The purpose of this study is to determine if TNS is safe and effective using a rigorous randomized active-control clinical trial design in 50 people with epilepsy.

Read the detailed description

Poorly controlled epilepsy is a disabling condition, affecting over one million Americans. Neurostimulation is a promising alternative for patients who have failed medical therapy, and who are not resective surgical candidates.

Trigeminal Nerve Stimulation (TNS) is a novel form of neurostimulation, and has a strong antiepileptic effect in an animal model of seizures. Preliminary data in humans indicates TNS is well tolerated and may be effective in people with intractable epilepsy.

TNS is an alternative mode of neurostimulation, because the Trigeminal Nerve can be stimulated in minimally-invasive fashion.

This is a randomized double blind study of Trigeminal Nerve Stimulation, which compares high stimulation to an active control. Subjects with poorly controlled partial onset seizures who meet all inclusion and exclusion criteria, enter a 6-week baseline period, and then are randomized in double-blind fashion to high or low intensity stimulation for 18 weeks. 50 subjects are to be enrolled at two sites.

Study outcomes are the following:

Percent change in seizure frequency during the treatment period compared with the baseline (pre-treatment) period.
Time to the 4th seizure

The primary comparisons will be between and within groups.

Conditions: Epilepsy, Seizure Disorders
Being tested: Trigeminal Nerve Stimulation
Keywords: partial seizures, poorly controlled epilepsy, intractable epilepsy, treatment resistant epilepsy, Trigeminal Nerve, Trigeminal Nerve Stimulation
Medical subject headings: Epilepsy, Seizures, Drug Resistant Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Trigeminal Nerve StimulationDevice
External stimulation of the supraorbital branch of the Trigeminal Nerve using a digital TENs unit

Study groups in NCT01159431
Study group	Role	What they receive
Active	Experimental	Not described Receives: Device: Trigeminal Nerve Stimulation
Control	Other	Not described Receives: Device: Trigeminal Nerve Stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

50% Responder Rate
Change in responder rate, at end of study (18 weeks)
Absolute percent of subjects with 50% reduction in seizures, 18 weeks compared with 6 weeks Note, the number is not a mean or median, but a fixed percentage.
Measured: Treatment period, 18 weeks (end of double blind period) compared with first 6 weeks
Time to the 4th Seizure
Number of Days to the 4th seizure
Measured: treatment period (18-weeks)
Change in Seizure Frequency
Percent change in seizure frequency from baseline
Measured: 18 weeks

Secondary outcomes (2)

Response Ratio: Mean Percent Change in Seizures
Response Ratio: Mean Percent Change in seizures over the treatment period, where [T-B] / [T+B] x 100%, where T = seizure frequency during the treatment period, and B = seizure frequency during the baseline period.
Measured: 18 weeks
Mood
Mean change in score on the Beck Depression Inventory. The Beck Inventory is a patient reported mood scale. The minimum score is 0, and the maximum score is 63. Scores of less than 10 are considered in the normal range. Scores above 10 are consistent with depression. Higher scores indicate higher degrees of depression, with scores of > 25 consistent with severe depression.
Measured: 18-weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2008Jun 2011

First posted9 Jul 2010 (estimated)
Study startJan 2008
Primary completionJun 2011
Study completionJun 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for EpilepsyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01159431
Sponsor's protocol ID: TNS-TDP-01
Status last verified: May 2013
First submitted: 7 Jul 2010
Last updated: 3 Jun 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

DeGiorgio CM, Murray D, Markovic D, Whitehurst T. Trigeminal nerve stimulation for epilepsy: long-term feasibility and efficacy. Neurology. 2009 Mar 10;72(10):936-8. doi: 10.1212/01.wnl.0000344181.97126.b4. No abstract available.
PubMed 19273830
DeGiorgio CM, Soss J, Cook IA, Markovic D, Gornbein J, Murray D, Oviedo S, Gordon S, Corralle-Leyva G, Kealey CP, Heck CN. Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy. Neurology. 2013 Feb 26;80(9):786-91. doi: 10.1212/WNL.0b013e318285c11a. Epub 2013 Jan 30.
PubMed 23365066

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Double Blind Study of External Trigeminal Nerve Stimulation for Intractable Epilepsy
ClinicalTrials.gov ID: NCT01159431
Acronym / sponsor ID: TNS-TDP-01
Conditions: Epilepsy, Seizure Disorders
Keywords: partial seizures, poorly controlled epilepsy, intractable epilepsy, treatment resistant epilepsy, Trigeminal Nerve, Trigeminal Nerve Stimulation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Olive View-UCLA Education & Research InstituteUniversity, hospital or other
Collaborators: Epilepsy Foundation, Boston Scientific Corporation
Study start: Jan 2008
Primary completion: Jun 2011 (actual)
Study completion: Jun 2011 (actual)
First posted: 9 Jul 2010 (estimated)
Results: Posted 3 Jun 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

TNS is an alternative mode of neurostimulation, because the Trigeminal Nerve can be stimulated in minimally-invasive fashion.

Study outcomes are the following:

Percent change in seizure frequency during the treatment period compared with the baseline (pre-treatment) period.
Time to the 4th seizure

The primary comparisons will be between and within groups.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Active	Experimental	Device: Trigeminal Nerve Stimulation
Control	Other	Device: Trigeminal Nerve Stimulation

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Ages 18 - 70;
No serious or progressive medical illness;
A history of intractable partial seizures;
At least two complex partial or tonic clonic generalized seizures per month in the last two consecutive months;
MRI or EEG consistent with localization-related or partial epilepsy;

Key exclusion criteria (6 listed)

History of non-epileptic seizures;
Inability to maintain accurate seizure calendars (self or caregiver);
Frequent use of benzodiazepines for clusters defined as greater than four times a month;
History of facial pain or trigeminal neuralgia;
Concurrent vagus nerve stimulation;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Trigeminal Nerve StimulationExternal stimulation of the supraorbital branch of the Trigeminal Nerve using a digital TENs unit	Device	Active, Control

Primary outcome

50% Responder Rate
Time frame: Treatment period, 18 weeks (end of double blind period) compared with first 6 weeks
Change in responder rate, at end of study (18 weeks) Absolute percent of subjects with 50% reduction in seizures, 18 weeks compared with 6 weeks Note, the number is not a mean or median, but a fixed percentage.
Time to the 4th Seizure
Time frame: treatment period (18-weeks)
Number of Days to the 4th seizure
Change in Seizure Frequency
Time frame: 18 weeks
Percent change in seizure frequency from baseline

2 secondary outcomes

Response Ratio: Mean Percent Change in Seizures
Time frame: 18 weeks
Mood
Time frame: 18-weeks

Results and safety

Results posted to the registry on 3 Jun 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active	25	23
Control	25	19

Primary outcome: 50% Responder Rate

Time frame: Treatment period, 18 weeks (end of double blind period) compared with first 6 weeks. Number. Unit: percentage of participants

Measure	Treatment n = 23	Control n = 19
Value	40.5	15.6

Primary outcome: Time to the 4th Seizure

Time frame: treatment period (18-weeks). Mean (Standard Deviation). Unit: days

Measure	Control Group-Baseline n = 25	Control Group-Double Blind Period n = 19	Treatment Group-Baseline n = 25	Treatment Group-Double Blind Period n = 23
Value	23 (19)	18 (31)	12.5 (18)	15 (28)

Primary outcome: Change in Seizure Frequency

Time frame: 18 weeks. Median (Standard Deviation). Unit: percentage change in seizures per month

Measure	Treatment n = 23	Control n = 19
Value	-16.1 (15.4)	-10.5 (11.1)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 18-weeks. Other adverse events reported at 4% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active	0 of 25 (0%)	5 of 25 (20%)	Not reported
Control	1 of 25 (4%)	4 of 25 (16%)	Not reported

Limitations and caveats (from the sponsor): Due to sample size and high variability in seizure frequency, median change did not achieve significance. To constrain variability, the RRATIO was used to assess seizure frequency. The RRATIO demonstrated within groups differences, p=0.04 ANOVA.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19273830DeGiorgio CM, Murray D, Markovic D, Whitehurst T. Trigeminal nerve stimulation for epilepsy: long-term feasibility and efficacy. Neurology. 2009 Mar 10;72(10):936-8. doi: 10.1212/01.wnl.0000344181.97126.b4. No abstract available.
Results publication: PubMed 23365066DeGiorgio CM, Soss J, Cook IA, Markovic D, Gornbein J, Murray D, Oviedo S, Gordon S, Corralle-Leyva G, Kealey CP, Heck CN. Randomized controlled trial of trigeminal nerve stimulation for drug-resistant epilepsy. Neurology. 2013 Feb 26;80(9):786-91. doi: 10.1212/WNL.0b013e318285c11a. Epub 2013 Jan 30.

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RecruitingObservational study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christopher M DeGiorgio, MD principal investigator

University of California, Los Angeles

Christi Heck, MD principal investigator

University of Southern California

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trigeminal Nerve Stimulation in people with Epilepsy and Seizure Disorders, run by Olive View-UCLA Education & Research Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

50% Responder Rate (time frame: Treatment period, 18 weeks (end of double blind period) compared with first 6 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01159431, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2013.