Myelomeningocele Clinical Trial
Official title:
Open Spina Bifida Fetoscopic Repair Project
The aim of the study is to assess a new fetal surgery approach to repair open spina bifida. The fetal group hypothesis is to perform a minimally invasive procedure using a fetoscopic technique in order to access to amniotic cavity and make the endoscopic repair. This approach will allow investigators to make the closure of the defect and avoid the use of an hysterotomy, reducing the risk of maternal complications as uterine dehiscence (rupture), hemorrhage and preterm premature rupture of membranes (PPROM), the patient also will be able to have a vaginal delivery.
Spina bifida can be a devastating neurological congenital anomaly . It results from
incomplete middleline closure of the neural tube between 22 and 28 embryological days. Its
incidence is approximately 1 per 1,000 / 2,000 births. It is considered the most common
congenital anomaly of the central nervous system that is compatible with life, 90% of the
defects are lumbar and sacral.
1. The most frequent form is myelomeningocele (MMC), characterized by the extrusion of the
spinal cord into a sac filled with cerebrospinal fluid (CSF), and is associated with
lower limb paralysis and bowel and bladder neurological dysfunction.
2. The majority of MMCs can be diagnosed between before 20 weeks. MMC is associated with
Chiari II malformation, which includes a constellation of anomalies such as hindbrain
herniation, brainstem abnormalities, low-lying venous sinuses and a small posterior
fossa.The Chiari II malformation can have deleterious effects on motor, cranial nerve
and cognitive functions. Postnatally most MMC patients develop hydrocephalus and require
a ventriculoperitoneal shunt. Shunts require lifelong monitoring and have a high failure
rate due to infection, obstruction, and fracture.
Experimental studies using animal models have shown that prenatal coverage of a spina
bifida-like lesion can preserve neurological function and reduce or reverse hindbrain
herniation.These studies suggest a "two-hit" hypothesis in which the ultimate neurologic
deficit results from a combination of the failure of normal neural-tube closure (first hit)
with secondary spinal cord injury resulting from prolonged exposure of sensitive neural
elements to the amniotic fluid (second hit mechanism).
Based on this hypothesis, open fetal surgical repair of MMC was proposed, and the recent
publication of the NICHD sponsored randomized controlled trial demonstrated clear neonatal
benefit of open in-utero fetal surgical repair of MMC. The study showed a reduction in the
incidence of hydrocephalus and in the radiographic severity of hindbrain herniation (relative
risk: 0.67; 95% confidence interval: 0.56-0.81).
Open in-utero fetal surgery is not without risk and the NICHD study (MOMS Trial) showed an
elevation in maternal-fetal morbidity/risk when compared to the postnatally treated group,
including higher risk for chorioamniotic separation (26% vs. 0%, respectively), maternal
pulmonary edema (6% vs. 0%), oligohydramnios (21% vs. 0%), placental abruption (6% vs. 0%),
spontaneous membrane rupture (46%; RR: 6.15; 95% CI: 2.75-13.78), spontaneous labor (38%; RR:
2.80, 95%CI: 1.51-5.18), maternal blood transfusion (9%; RR: 7.18; 95%CI: 0.90-57.01), and
preterm delivery before 34 weeks (46%; RR: 9.2; 95%CI: 3.81-22.19). The reason for the
increased incidence of these complications is related to the nature of the open fetal
procedure, which involves a multi-faceted invasive approach including maternal laparotomy,
large hysterotomy with uterine edge stapling, and open fetal repair of the spina bifida
defect that may involve manipulation and exposure of the fetus for a significant amount of
time.
Fetal endoscopic surgery has progressed rapidly over the past decades and the investigators
are now able to perform a number of intricate procedures inside the uterus with specially
designed instruments. These procedures include laser therapy for Twin-twin-transfusion
syndrome, fetal cystoscopy and fulguration of posterior urethral valves, release of amniotic
bands, and placement of various shunts and balloons inside fetal structures and cavities
(peritoneal, pleural, cardiac, and trachea).
Fetoscopy offers a less invasive therapeutic option that could reduce a number of the
morbidities (both maternal and fetal) related to open fetal procedures.
A few animal studies and some clinical human experience with fetoscopic repair of MMC have
been reported showing the feasibility of covering the defect with a patch and sealant, or
even in performing a full repair. These repairs have been accomplished using at least two
(and sometimes more) entry ports through the uterine wall. Kohl et al. in Germany, have
demonstrated the feasibility of performing a complete percutaneous fetoscopic repair of MMC
using carbon dioxide to distend the uterus and provide a dry working area for the surgeon to
perform the repair.
These investigators described a two-layer covering technique using an absorbable patch
(Durasis, Cook, Germany) and sutures. However, while they showed that the procedure is
feasible, their percutaneous technique with complete two layer surgical closure of the defect
using sutures was associated with prolonged operative time and significant maternal and
obstetrical morbidities.
Fetoscopy in a CO2 gas filled uterus has been recently reported by groups in Bonn, Germany
(Kohl et al) and Sao Paulo, Brazil (Pedreira et al). The fetoscopic technique the
investigators use has been developed and tested in a fetal sheep model of MMC by the
investigators group and others (Peiro et al). This fetoscopy technique has now been employed
by a group of investigators, in human fetal surgery cases in Houston, Texas, Monterrey México
and in Shiraz, Iran showing its feasibility and applicability to the human uterus and fetus,
and demonstrating an improved degree of flexibility in terms of access to the fetus
regardless of placental location. The technique is designed to decrease the maternal risks of
open uterus fetal surgery while maintaining a similar level of fetal benefit as seen in the
MOMS trial.
The investigators technique employs general deep anesthesia and an open abdomen/exteriorized
(but closed) uterus methodology that allows the minimally invasive closure of the fetal
neural tube using the same closed skin repair currently employed at another US centers using
the open uterus approach. The technique employs a novel approach to low pressure uterine
distention using the same carbon dioxide gas 8-12 mmHg that others attempting fetoscopic
repair have used, but employing a much lower gas flow rate and pressure. In addition, this
technique allows a significantly quicker neural tube repair because of improved access to the
fetus, ability to manipulate the fetus into the required position, and superior port
placement resulting from the exteriorized maternal uterus.
The technique consist in a three access ports (10 French each) and these can be sutured into
the uterus allowing a closed seal and minimizing gas leakage. Finally, a 2-3 mm Storz
surgical sets enables a full surgical repair to be performed via a fetoscopic approach.
There have been reports about sheep model, with dual access port fetoscopic neural tube
closure using a 12 french cannula, a second 9 french cannula, a cover patch, and a medical
sealant with similar results to that seen with open fetal surgical repair in the same sheep
model. Using the knowledge and expertise gained with more than 3 years of experience in
fetoscopic sheep surgery, Dr. Peiro has now performed 8 minimally invasive repairs on human
patients in Barcelona (Vall D'Hebron Hospital, Instituto Nacional de Perinatologia, Mexico
City, Mexico). Also there have been reports at Texas Childrens Hospital ( Belfort) using two
ports technique in order to successfully repair the defect.
The neurosurgical repair proposed in this protocol will involves release of the placode,
dissection of the surrounding skin and attempted primary closure of the defect using
available skin. In those cases where the investigators are able to complete the procedure
with full skin closure of the defect, the only difference between the open uterus procedure
and the fetoscopic procedure, will be that the surgery will be done fetoscopically rather
than through an open uterine incision. If the investigator group is unable to close the skin
primarily despite best fetoscopic efforts, the option of performing/completing the repair as
an open procedure exists and will be offered to the patient previous counselling of the
maternal morbidity. The patient is monitored in hospital until ready for discharge.
Approximately 6 weeks after the surgery a post-procedure fetal MRI will be performed. If
there is evidence of good closure of the neural tube defect and reversal of the Chiari II
malformation, a vaginal delivery can be attempted based on obstetric criteria. Patients will
be followed in person every 3-4 months after birth to 12 months at the Spina Bifida Clinic at
Christus Muguerza Alta Especialidad. Remaining visits will be yearly up to 5 years. If this
is not possible, questionnaire(s) will be mailed to the participants and records will be
requested from the treating neurosurgeon on this same schedule.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06042140 -
Cryopreserved Human Umbilical Cord as a Meningeal Patch in Fetoscopic Spina Bifida Repair
|
N/A | |
Completed |
NCT04468568 -
In Utero Repair of Myelomeningocele: Atosiban Versus Terbutaline
|
||
Recruiting |
NCT03856034 -
Laparotomy Versus Percutaneous Endoscopic Correction of Myelomeningocele
|
N/A | |
Recruiting |
NCT04362592 -
In-Utero Endoscopic Correction of Spina Bifida
|
N/A | |
Active, not recruiting |
NCT03936322 -
Minimally Invasive Fetoscopic Regenerative Repair of Spina Bifida - A Pilot Study
|
N/A | |
Not yet recruiting |
NCT06405698 -
Role of Perforator Flaps in Back Defects Reconstruction
|
N/A | |
Active, not recruiting |
NCT00175123 -
Effect of Botulinum Toxin in Neurogenic Bladders in Children With Myelomeningocele
|
Phase 4 | |
Completed |
NCT02390895 -
Prenatal Endoscopic Repair of Fetal Spina Bifida
|
N/A | |
Active, not recruiting |
NCT03090633 -
Fetoscopic Repair of Isolated Fetal Spina Bifida
|
N/A | |
Not yet recruiting |
NCT03088761 -
Cuff Pressure in Infants
|
N/A | |
Active, not recruiting |
NCT04484441 -
Maternal-fetal Immune Responses to Fetal Surgery
|
||
Recruiting |
NCT04738539 -
Efficacy of Contrast Enhanced Voiding Urosonography for Urodynamic Studies
|
||
Recruiting |
NCT04652908 -
Cellular Therapy for In Utero Repair of Myelomeningocele - The CuRe Trial
|
Phase 1/Phase 2 | |
Terminated |
NCT02493062 -
Evaluation of Hysterotomy Site After Open Fetal Surgery
|
N/A | |
Completed |
NCT03550898 -
Can Dynamic Ultrasonography Replace Urodynamics in Follow-up of Patients With Myelomeningocele
|
N/A | |
Active, not recruiting |
NCT04251806 -
Sleep-disordered Breathing in Infants With Myelomeningocele
|
||
Terminated |
NCT02509377 -
Fetal Myelomeningocele Repair With Maternal BMI Between 35.0 and 40.0
|
N/A | |
Recruiting |
NCT03788122 -
Fetal Surgery Interview Study: Parental Perceptions of Fetal Surgery
|
N/A | |
Completed |
NCT02664207 -
Extended Criteria For Fetal Myelomeningocele Repair
|
N/A | |
Recruiting |
NCT03315637 -
Fetal Endoscopic Surgery for Spina Bifida
|
N/A |