In-Utero Endoscopic Correction of Spina Bifida

In-Utero Endoscopic Correction of Spina Bifida: Laparotomy-Assisted or Percutaneous

The purpose of this study is to evaluate the feasibility and effectiveness of performing fetoscopic surgical correction of fetal spina bifida. Two surgical approaches will be utilized: the percutaneous technique versus the laparotomy/uterine exteriorization technique.

Study Overview

• Status: Recruiting
• Conditions: Neural Tube Defects; Myelomeningocele; Spina Bifida
• Intervention / Treatment: Device: In Utero Endoscopic Correction of Myelomeningocele IDE - Percutaneous Technique; Device: In Utero Endoscopic Correction of Myelomeningocele IDE - Laparotomy/Uterine Exteriorization Technique

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ruben Quintero, MD; Phone Number: 720-753-3825; Email: q@the-fetal-institute.com
• Study Contact Backup: Name: Ramen Chmait, MD; Phone Number: 213-469-6277; Email: chmait@usc.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Hollywood Presbyterian Medical Center
      • Contact: Ramen Chmait, MD; Phone Number: 213-469-6277; Email: chmait@usc.edu
      • Contact: Arlyn Llanes, RN; Phone Number: 213-469-6277; Email: arlyn.llanes@med.usc.edu
  • Florida
    • Wellington, Florida, United States, 33141
      • Recruiting
      • Wellington Regional Medical Center
      • Contact: Ruben Quintero, MD; Phone Number: 720-753-3825
      • Contact: Eftichia Kontopoulos, MD; Phone Number: 720-753-3825

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 52 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Myelomeningocele (including myeloschisis) at level T1 through S1 with hindbrain herniation. Lesion level and hindbrain herniation will be confirmed by MRI and ultrasonography.
2. Maternal age ≥18 years.
3. Gestational age of 19 to 27 6/7 weeks' gestation as determined by clinical information and evaluation of first ultrasound.
4. Balanced karyotype and/or normal mircoarray with written confirmation of culture results. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is at 24 weeks or more.
5. Positive evaluation of social work consult indicating the patient is capable of consenting to the procedure and has the appropriate social support system to participate in the study.
6. Positive evaluation from pediatric neurology consult.
7. Willing to return to our center, or to a multi-disciplinary spina bifida clinic closer to their home for the 6, 12, 24, 30, 48, and 60 months follow-up evaluations.

Exclusion Criteria:

1. Multiple gestation
2. Insulin-dependent pregestational diabetes
3. Presence of a fetal anomaly not related to Chiari II Malformation. A fetal echocardiogram will be conducted before surgery and if the finding is abnormal, the patient will be excluded.
4. Fetal kyphosis of 30 degrees or more, assessed by ultrasound or MRI.
5. Presence of uterine cervical cerclage or history of incompetent cervix.
6. Placenta previa or placental abruption.
7. Short cervix < 25 mm measured by cervical ultrasound.
8. Obesity as defined by body mass index (BMI) of 40 or greater.
9. History of previous spontaneous singleton delivery prior to 37 weeks.
10. Maternal-fetal Rh isoimmunization, Kell sensitization or a history of neonatal alloimmune thrombocytopenia.
11. Maternal HIV or Hepatitis-B status positive because of the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or Hepatitis B status is unknown, the patient must be tested and found to have negative results before she can be enrolled.
12. Known Hepatitis-C positivity. If the patient's Hepatitis C status is unknown, she does not need to be screened.
13. Uterine anomaly such as large (greater than 6 cm) fibroids, cervical fibroids or multiple fibroids or Mullerian duct abnormality.
14. Other maternal medical condition which is a contraindication to surgery or anesthesia.
15. Patient does not have a support person (e.g., husband, partner, parents).
16. Inability to comply with the travel and follow-up requirements of the study.
17. Patient does not meet psychosocial criteria as determined by the social worker evaluation.
18. Participation in another intervention study that influences maternal and fetal morbidity and mortality.
19. Maternal hypertension as determined by the investigator, which would increase the risk of preeclampsia or preterm delivery (including, but not limited to: uncontrolled hypertension, chronic hypertension with end organ damage and new onset hypertension in current pregnancy).
20. Bicornuate uterus or any other uterine malformation the PI decides is not safe for surgery.
21. Nickel allergy.
22. Maternal request to undergo open fetal surgery for the antenatal correction of OSB at our institution primarily or after failed fetoscopic approach.
23. Known maternal hypersensitivity to bovine collagen or chondroitin materials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Laparotomy/Uterine Exteriorization Technique; The laparotomy/uterine exteriorization technique consists of performing a laparotomy (incision into the abdominal cavity), exteriorizing the uterus, and using endoscopic scopes through the uterus to perform the correction.	Device: In Utero Endoscopic Correction of Myelomeningocele IDE - Laparotomy/Uterine Exteriorization Technique; The laparotomy/uterine exteriorization technique uses endoscopes through an open abdomen and closed, exteriorized uterus to perform the spina bifida correction.
Experimental: Percutaneous Technique; The percutaneous technique uses endoscopic scopes through the maternal skin and uterus to perform the surgery. A variation of the percutaneous technique is the mini-laparotomy technique, which uses an endoscopic scope through an incision on the abdomen, smaller than a laparotomy ("mini-laparotomy"), and smaller endoscopic scopes through the maternal skin and uterus to perform the surgery.	Device: In Utero Endoscopic Correction of Myelomeningocele IDE - Percutaneous Technique; The percutaneous approach uses endoscopes through a closed maternal abdomen and closed uterus to perform the spina bifida correction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to perform the endoscopic procedure	Successful fetoscopic closure of the defect	At time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chiari II malformation reversal	Reversal of hindbrain herniation on ultrasound and MRI	Prior to delivery

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: USFetus
• Investigators: Principal Investigator: Ramen Chmait, MD, University of Southern California; Principal Investigator: Ruben Quintero, MD, US Fetus

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2018
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): October 31, 2031

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 12, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Nervous System Malformations; Meningomyelocele; Spina Bifida Cystica; Neural Tube Defects; Spinal Dysraphism
• Other Study ID Numbers: HS-05-00374

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes