Clinical Trial Details
— Status: Withdrawn
Administrative data
| NCT number |
NCT04102254 |
| Other study ID # |
Pro00103374 |
| Secondary ID |
|
| Status |
Withdrawn |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 7, 2023 |
| Est. completion date |
January 10, 2025 |
Study information
| Verified date |
August 2022 |
| Source |
Duke University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In this study, the investigator aims to perform cortical stereo electroencephalogram (sEEG)
recordings during simultaneous anterior nucleus of the thalamus (ANT) recording and
stimulation to better understand the following: 1) how the ANT is involved in various seizure
types; 2) which cortical regions are modulated by established ANT stimulation patterns; and
3) how novel ANT stimulation patterns modify epileptogenic cortical activity. Together, this
knowledge will advance ANT deep brain stimulation (DBS) therapy by providing a physiologic
basis for patient selection for ANT DBS, while identifying brain signals and stimulation
patterns that can be used to develop novel methods for ANT DBS. Up to 15 adult patients (18
and older) who present to Duke Neurosurgery for routine seizure localization using sEEG will
be asked to enroll in this pilot study of ANT recording and stimulation. In the course of
surgical epilepsy treatment, patients routinely undergo surgical placement of sEEG electrodes
for the purposes of seizure localization. During this procedure, 2 additional leads will be
placed in the ANT. These patients remain hospitalized for 7-14 days after sEEG placement,
during which time their seizure medications are tapered. Concurrent video monitoring is
performed while continuous neural recordings are made through the sEEG electrodes.
Additionally, continuous recordings will be performed through the electrodes placed in the
thalamus. Periodically, standard intermittent high-frequency stimulation (130 Hz, 90-ms pulse
width, and 2 mA intensity) will be performed with a 60-s on and a 300-s off cycle after
surgery. These standard ANT stimulation parameters are employed clinically. Data will include
the sEEG recordings marked for ANT stimulation, any side effects, medications, past medical
history (PMH), and tests/procedures during the hospital stay. Risks involved are as described
for the standard depth electrode surgery with the addition of the possible side effects from
the stimulation which include sensations of numbness and tingling, and possibly increased
seizure activity.
Description:
The purpose of this research is to examine the physiologic underpinnings of deep brain
stimulation of the anterior nucleus of the thalamus (ANT), a method reducing seizures in
adults diagnosed with medically refractory epilepsy. In this study, the investigator aims to
perform cortical stereo electroencephalogram (sEEG) recordings during simultaneous ANT
recording and stimulation to better understand the following: 1) how the ANT is involved in
various seizure types; 2) which cortical regions are modulated by established ANT stimulation
patterns; and 3) how novel ANT stimulation patterns modify epileptogenic cortical activity.
Together, this knowledge will advance ANT DBS therapy by providing a physiologic basis for
patient selection for ANT DBS, while identifying brain signals and stimulation patterns that
can be used to develop novel methods for ANT DBS.
Approximately 3 million people in the United States experience epilepsy. Despite medical
therapy, up to 30% of these patients continue to experience recurrent seizures. In this
medically refractory population, tissue resection or ablation offer a high likelihood of
seizure freedom, if a single epileptogenic focus can be precisely identified. For patients
who are not candidates for resection or ablation, or those who continue to have seizures
after these treatments, neuromodulation represents an alternative therapeutic option. One
such therapy, deep brain stimulation (DBS) has been approved for around 5 years in Europe and
was recently approved in the United States as a treatment for medically refractory epilepsy.
A number of potential DBS targets are being investigated, particularly, the ANT, which
consists of the anteroventral, anterodorsal, and anteromedial nuclei. The ANT was recognized
as a potential target because of its central connectivity to cortical regions where seizures
often originate. Several pilot studies and recent trials have demonstrated 5-year efficacy
and safety outcomes for ANT DBS. In a large randomized controlled study of ANT stimulation
with long-term follow-up, there was a 56% median seizure reduction at the 2 year, and a 69%
median and seizure reduction at the 5 year, in patients with drug-resistant focal epilepsy.
This study also suggested that patients with temporal lobe epilepsy achieved greater benefit
than those with extra-temporal or multifocal seizures. Since these pivotal trials, DBS of the
ANT has emerged as a promising therapy for focal drug resistant epilepsy, however, its basic
mechanism of action is unclear. One study which examined cortical local field potentials
recordings during high-frequency ANT stimulation (130 Hz), has suggested that epileptic
network desynchronization is a potential mechanism of DBS of the ANT.
