Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04806516 |
| Other study ID # |
49155 |
| Secondary ID |
1UH3NS1005494934 |
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2021 |
| Est. completion date |
June 30, 2024 |
Study information
| Verified date |
October 2023 |
| Source |
Baylor College of Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This research study is for participants that have been diagnosed with intractable Obsessive
-compulsive disorder (OCD). OCD is a persistent and oftentimes disabling disorder marked by
unwanted and distressing thoughts (obsessions) and irresistible repetitive behaviors. OCD
affects 2-3% of the US population, and is responsible for substantial functional impairment
and increased risk of early death.
The only established first-line treatments for OCD are cognitive-behavioral therapy (CBT)
with exposure and response prevention and certain medications. About 30-40% of patients fail
to respond and few experience complete symptom resolution. Up to 25% of patients have
difficulty tolerating CBT and the risk of relapse after therapies remains large. For the most
severe cases, neurosurgery (surgery in the brain), has long been the option of last resort.
In this study the investigators want develop an adaptive Deep Brain Stimulation (aDBS) system
to use in subjects with intractable (hard to control) OCD. Deep brain stimulation (DBS)
remains investigational for OCD patients and is not considered standard therapy. DBS involves
the surgical implantation of leads and electrodes into specific areas of the brain, which are
thought to influence the disease. A pack implanted in the chest, called the neurotransmitter,
keeps the electrical current coursing to the brain through a wire that connects the
neurotransmitter and electrodes. It is believed DBS may restore balance to dysfunctional
brain circuitry implicated in OCD. The goal of this study is to enhance current approaches to
DBS targeting in the brain and to use a novel approach to find a better and more reliable
system for OCD treatment.
This current research protocol will focus on the completion of Phase II which will implant
the RC+S system with ECoG paddles in 5 subjects.
Description:
ENROLLMENT: A subject is considered enrolled upon signing informed consent and deemed
eligible to be screened by the investigator. The informed consent process may include
discussions with the patients family and referring clinician. Medical records that can be
obtained will be carefully reviewed to determine adequacy of past treatments including
Cognitive Behavioral Therapy (CBT).
A subject identification number will be assigned to each subject that signs consent. This
number will be used to identify the subject and must be used on all study documentation
related to that subject throughout the study.
SCREENING: Potential subjects meeting inclusion/exclusion criteria and willing to participate
in the study as demonstrated by signing the informed consent will be enrolled in the study
and undergo 2 screening visits (Visit 1 and Visit 2) spaced over an approximate 1 month
period. Diagnostic and screening ratings are completed, followed by complete medical,
neurological and neurosurgical evaluations. Final selection of candidates will be made by
consensus of the multi-disciplinary investigator team (Project Advisory Committee).
Neuroimaging Methods:
The Core for Advanced MR Imaging (CAMRI) is a state-of-the-art resource housing 3 cutting
edge MRI systems for the Houston research community, located at BCM Main Campus. CAMRI will
perform the research 3T MRI scans, which will be collected on all subjects (DBS and control)
using the Prisma scanner for consistency. All subjects will be escorted to CAMRI by the study
team.
DBS implanted subjects will undergo two 3T MRI Scans prior to surgery (1 research MRI at
CAMRI and 1 clinical MRI at Baylor St. Luke's Medical center (BSLMC). DBS implanted subjects
will under 4 Magnetoencephalography (MEG) scans total.
Control subjects will undergo one 3T MRI scan (research MRI scan at CAMRI). Control subjects
will also undergo 4 MEG scans.
TREATMENT: Subjects eligible for DBS implantation will also have an additional clinical,
pre-surgical 3T MRI scan performed at baseline. This scan will be performed on a Philips
scanner at Baylor St. Luke's Medical Center (BSLMC). This scan is necessary in order to
potentially screen out individuals presenting with brain abnormalities which would not be
compatible with the surgery (e.g., congenital defects, lack of normal anatomic correlates)
and to assist with surgical planning.
All Subjects (DBS and control) will also undergo MEG scans. This is also needed as a baseline
assessment as MEG scans will also be performed post implantation at 2 weeks, 6 months, and 12
months on a MEG scanner at the Texas Childrens Hospital in the Houston Medical Center.
Chest X-ray and EKG will also be performed on OCD subjects eligible for DBS.
Age/gender matched non-implanted subjects will serve as controls. They will undergo
1-research 3T MRI and 4 MEG scans using the same imaging protocol and at the same time points
as OCD implant subjects to control for non-DBS effects on rs-fc.
1. Unless collected prior to the day of surgery, a head CT will be performed on the morning
of surgery for stereotactic planning.
2. Employing local anesthetic (with or without sedation as clinically indicated), a
stereotactic headframe (Leksell Model G, Elekta Instruments, Atlanta, GA, USA) will be
attached to the subjects skull on the morning of surgery in the operating room.
3. A 3D volumetric image (O-Arm 2, Medtronic Inc, Boulder, CO, USA) will be performed for
purposes of defining the volumetric stereotactic headspace.
4. The images will be uploaded onto a Computer Workstation (Stealth S7, Medtronic, Inc.,
Boulder, CO, USA) equipped with stereotactic planning software (Cranial 3.0) for the
purpose of planning the surgery. The preoperative 3T MRI obtained prior to the surgical
date, will be fused with the CT scan in the surgical planning station. The initial
target point within the ventral striatum will be chosen based on the subjects specific
anatomy. The surgical trajectory to this point will also be planned in order to avoid
prominent vessels, the sulci, and the ventricles. The computer will generate the X, Y
and Z coordinates to set on the frame as well as the coronal and sagittal angles of
approach required to establish the desired trajectory and target point. This initial
target point will be modified by the subjects specific anatomy as determined by the
preoperative 3T scans. The final target coordinates will be determined during this
analysis.
5. While the surgeon is planning the procedure, the subject will be positioned supine on
the operating table. A Foley catheter will be inserted. Antibiotics will be administered
intravenously and vital signs will be monitored. The stereotactic head frame will be
fixed to the operating table for subject safety, with the head elevated for subject
comfort. A sterile prep and drape will be performed.
6. The target coordinates will be set on the stereotactic frame bringing the target point
to the center of the operating arc. Additional local anesthetic will be given at the
point of incision. Following incision, a 14 mm burr hole will be made employing a
self-stopping perforator. The burr hole cap provided with the DBS lead will be secured
to the skull with two screws. The dura will be coagulated and incised. The pial surface
will be gently coagulated and a small incision will be made to allow easy entry of the
electrode guides, which will be inserted to the brain according to standard stereotactic
protocol.
7. Once the above adjustments have been made, the DBS quadripolar electrode (model 3387;
Medtronic Inc., Minneapolis, MN, USA) will be inserted through the guide tube to the
target point. Reticles will be attached to the frame and intraoperative imaging will be
employed to confirm that the lead tip is positioned at the target and assess for the
presence of intracerebral hemorrhage. Sedation will be withdrawn. An extension cable
will be connected to the lead sterilely and the other end will be passed off the field
to be connected to an external pulse generator so that test stimulation may be
performed. Test stimulation will be performed via each contact to 1) assess for
stimulation-induced side effects and 2) monitor for acute changes in behavior using a
Likert-type scale to assess anxiety, arousal, and mood. Intra operative behavioral
testing of stimulation will be videotaped.
8. Phase II addition of ECoG. In order to achieve optimal coverage of the orbitofrontal
cortex (OFC) region, the investigators will place a subdural cortical strip electrode
over this region of cortex. There is well-established precedent for using strip
electrodes over the OFC cortical surface, both in sub-acute (<1 month) and chronic
(years/permanent) clinical settings. OFC strip electrodes have been commonly placed via
a burr hole in the inferior frontal region for epilepsy monitoring. The electrodes used
in these applications are usually 4 to 8 contacts, spaced 1 cm apart. These are
typically sub-acute placements lasting days to weeks, and this practice has been common
across the U.S. and world for decades. Strip electrodes covering OFC have also been used
as permanent implants in the responsive neurostimulation (RNS) system, which is FDA
approved and clinical standard of care for the treatment of medically refractory
epilepsy. The strip electrodes used in this case are 4 contacts spaced 1 cm apart. In
communications with the RNS device manufacturer, the investigators estimate that 100s of
such electrodes have been placed in patients in this country. Our placement procedure
will be very similar to that used for RNS OFC strip electrodes. The investigators will
use the 09130 Subdural Quadripolar Paddle Lead, which is also 4 contacts spaced 1 cm
apart. The investigators will create a burr hole in the inferior frontal region. The
investigators will use standard frameless navigation to choose a location of the burr
hole that facilitates a direct line of sight along the horizontal floor of the anterior
cranial fossa within which lies the OFC region. The investigators will make a
cosmetically acceptable incision approximately the same size as that used for the
traditional DBS lead. The investigators will use monopolar cautery to deepen the
incision past the temporalis muscle and create a standard size burr hole. The
investigators will open the dura and visualize the inferior frontal lobe and floor of
the anterior cranial fossa. Under direct vision, the investigators will place the strip
electrode using irrigation to permit smooth placement, paying careful attention not to
damage cortical vasculature. Bridging veins between dura and cortex are extremely rare
in this region, thus increasing the safety profile of the procedure. Once the electrode
is in place, the investigators will suture its tail to the dura in the burr hole to
provide an anchor point. The investigators will then use a small metal plate to affix
the electrode tail to the outer aspect of the skull near the burr hole to further anchor
the electrode. The investigators will use a small length of plastic tubing available in
the electrode kit as a shock absorber around the electrode tail at this fixation point
to avoid chronic mechanical damage to the electrode tail from contact with the plate.
The investigators place fibrin glue within the burr hole to prevent leak of
cerebrospinal fluid. The investigators will close the muscle with dissolvable sutures,
tunnel the tail to the DBS lead burr hole, and close the incision in standard fashion.
From the site of the DBS lead burr hole, the two electrode tails (one for the DBS lead
and the other for the OFC strip electrode) will be tunneled towards the ipsilateral IPG
site in standard fashion.
9. Intra-operative X-ray imaging may be performed as needed (up to 4 times per side) to
ensure proper target has been reached.
10. A post-implantation 3D volumetric scan will be performed to confirm the electrode
position.
11. Steps 5-9 above will be performed to insert the second DBS lead and ECoG paddle in the
other hemisphere to complete implantation of all electrodes.
12. If there are no untenable side effects, the leads will be secured to the skull with the
burr hole caps. The free end of the leads will be left in the sub-galeal space and the
incisions will be closed in anatomical layers.
13. The headframe will be removed and general anesthesia will be induced. Two Olympus RC+S
pulse generators will then be implanted in the subclavicular region and connected to the
deep brain and cortical leads via extension cables (two IPGs, each driving one cortical
and one subcortical lead).
14. A post-operative CT scan will be performed prior to discharge to ensure that an
intracerebral hemorrhage has not occurred.
15. The subject will be taken to the Recovery Room or the Neurosurgery ICU for post-
operative monitoring (See below) and will be discharged from the hospital after at least
one night of observation and when clinically stable. A Basic Metabolic Panel (BMP) may
be run on the subject to confirm they are clinically stable.
16. The subject will return to the neurosurgery clinic (Visit 4) for post-operative
evaluation according to normal clinical practice (approximately 1 week after surgery).
The wounds will be inspected and the subjects neurological status will be assessed.
Sutures will be removed.
DBS Programming:
Initially, a monopolar survey will be conducted with frequency set to 150 Hz and pulse width
to 90 microseconds. Constant current amplitude will be used and increased in a step-wise
fashion as tolerated and without exceeding current density upper limits. The constant current
setting is particularly useful in the early weeks to months following surgery when impedances
are still changing. In order to elicit a mirth response, amplitude needs to return to 0
microamps for about 30 seconds before testing the next increment. For example, if 2mA, C+1,
90usec, 150Hz is ineffective, then amplitude is reduced to 0mA for 30 seconds and then
rapidly increased to 4mA, C+1-, 90usec, 150Hz. Soft start needs to be turned off. Bipolar
settings will also be tested and need to be used during rsfMRI. DBS parameters will be
optimized/adjusted based on clinical evaluation of mood and anxiety and to minimize side
effects. The following observed effects will be recorded via a scale used in a past study:
facial expression, nervousness, alertness, and positive or negative affect. Facial expression
will be measured using the AFAR system. AFAR will measure the maximum intensity and velocity
of the smile response in action units. Participants faces will be recorded on video as their
stimulation is increased to elicit the mirth response. Changes in facial expression using
facial muscles of orbicularis oris (muscle that encircles the mouth) zygomaticus (major and
minor muscles of the angle of the mouth) will be recorded. This information will be used to
train a classifier to recognize that stimulation intensity is too great. The investigators
will also have the subject self-report on changes in mood, anxiety, energy and side effects.
