In-Utero Surgery Techniques for Spina Bifida

Recruiting at 2 trial locations

Overseen By Ramen Chmait, MD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Southern California

Disqualifiers: Multiple gestation, Diabetes, Obesity, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new surgical techniques to correct spina bifida in unborn babies. Spina bifida, a condition where the spine and spinal cord do not form properly, is the focus of this trial, which tests two surgical methods performed before birth using small instruments and cameras. The trial examines the In Utero Endoscopic Correction of Myelomeningocele IDE - Laparotomy/Uterine Exteriorization Technique and the In Utero Endoscopic Correction of Myelomeningocele IDE - Percutaneous Technique. It targets expectant mothers whose babies have myelomeningocele, a type of spina bifida confirmed by MRI or ultrasound scans. Participants must be prepared for follow-up visits for up to five years and have a strong support system. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research that could improve surgical outcomes for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these surgical techniques are safe for fetal spina bifida correction?

Research has shown that both surgical methods for correcting spina bifida before birth are promisingly safe for mothers and babies. The first method, called laparotomy/uterine exteriorization, involves making a cut in the mother's belly to reach the uterus and perform the surgery. Studies have found this method to be safe for mothers and effective in fixing the baby's neural tube defect.

The second method, known as the percutaneous technique, uses small tools inserted through the mother's skin and uterus. This approach aims to lower risks for the mother while still providing good results for the baby, especially regarding brain and spine health.

Various studies have tested both techniques, offering ways to reduce complications while treating spina bifida before birth. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these in-utero surgery techniques for spina bifida because they aim to address the condition before birth, potentially reducing complications and improving outcomes compared to postnatal surgeries. The Laparotomy/Uterine Exteriorization Technique involves making an incision in the abdominal cavity to access the uterus, allowing for precise endoscopic correction through the uterus itself. Meanwhile, the Percutaneous Technique offers a less invasive approach, using endoscopic scopes through the mother's skin and uterus, which could mean shorter recovery times and reduced risks for both mother and baby. These innovative methods may provide more effective, earlier intervention options for spina bifida than traditional postnatal surgeries.

What evidence suggests that these surgical techniques are effective for spina bifida?

Research has shown that performing surgery on a baby with myelomeningocele, a severe form of spina bifida, while still in the womb can lead to better health outcomes. In this trial, participants may undergo the traditional Laparotomy/Uterine Exteriorization Technique. This method involves opening the mother's abdomen and uterus to protect the baby's nerve tissue, potentially improving the baby's ability to move and control bladder and bowels after birth. Alternatively, participants may receive the Percutaneous Technique, a less invasive method that uses smaller cuts and offers greater safety for the mother. This newer method has been found to be just as effective as the traditional surgery, providing similar health benefits for the baby. ^{1 2 6 7 8}

Who Is on the Research Team?

Ruben Quintero, MD

Principal Investigator

US Fetus

Ramen Chmait, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for pregnant women over 18 with a fetus diagnosed with spina bifida (T1-S1 level) and hindbrain herniation, between 19-27 weeks' gestation. Candidates must have normal genetic test results, be able to consent and follow the study plan, and have support systems in place. Exclusions include multiple pregnancies, certain maternal health issues like diabetes or obesity (BMI ≥40), previous early deliveries, positive HIV/Hepatitis-B status or other conditions that risk surgery/anesthesia.

Inclusion Criteria

Gestational age of 19 to 27 6/7 weeks' gestation as determined by clinical information and evaluation of first ultrasound

Willing to return for follow-up evaluations at specified intervals

I have a spinal defect from T1 to S1 with brain tissue protrusion, confirmed by MRI and ultrasound.

Exclusion Criteria

You are extremely overweight, with a body mass index (BMI) of 40 or higher.

You have placenta previa or placental abruption.

If you have high blood pressure during pregnancy that could lead to complications like preeclampsia or having a baby too early, you may not be able to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Fetoscopic surgical correction of fetal spina bifida using either the percutaneous or laparotomy/uterine exteriorization technique

At time of surgery

Follow-up

Participants are monitored for safety and effectiveness after the surgical procedure

Until delivery

What Are the Treatments Tested in This Trial?

Interventions

• In Utero Endoscopic Correction of Myelomeningocele IDE - Laparotomy/Uterine Exteriorization Technique
• In Utero Endoscopic Correction of Myelomeningocele IDE - Percutaneous Technique

Trial Overview The trial tests two surgical methods to correct fetal spina bifida before birth: one through small incisions using cameras (percutaneous technique) and another by opening the abdomen to access the uterus directly (laparotomy/uterine exteriorization). The goal is to see which method might be safer or more effective.

How Is the Trial Designed?

Group I: Percutaneous Technique Experimental Treatment 1 Intervention

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.

Group II: Laparotomy/Uterine Exteriorization Technique Experimental Treatment 1 Intervention

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.

In Utero Endoscopic Correction of Myelomeningocele IDE - Laparotomy/Uterine Exteriorization Technique is already approved in United States, European Union for the following indications:

Approved in United States as Fetal Spina Bifida Repair for:

• Severe myelomeningocele in fetuses between 19 and 26 weeks of gestation

Approved in European Union as In Utero Endoscopic Correction of Myelomeningocele for:

• Fetal spina bifida with myelomeningocele lesions located between T1 and S1

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

USFetus

Collaborator

Trials

2

Recruited

120+

Published Research Related to This Trial

Fetal surgery for repairing meningomyelocele has shown improved neurological and psychomotor outcomes, but traditional open surgery poses significant risks to the mother.

Endoscopic techniques for fetal repair are being developed and tested, showing promise for lower maternal morbidity, suggesting they may become the preferred method for this procedure in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fetoscopy for meningomyelocele repair: past, present and future. Bevilacqua, NS., Pedreira, DA.[2018]

In a study of 378 pregnant patients undergoing fetal myelomeningocele repair, both open and endoscopic approaches showed similar rates of fetal complications, such as intrauterine fetal demise and preterm delivery, indicating comparable safety profiles for both methods.

However, the endoscopic approach was associated with a higher rate of intrauterine infections (4.2%) compared to the open approach (0%), suggesting a potential risk that needs to be considered when choosing the surgical method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open and endoscopic fetal myelomeningocele surgeries display similar in-hospital safety profiles in a large, multi-institutional database. Mikulski, MF., Well, A., Beckerman, Z., et al.[2023]

Intrauterine surgery for repairing fetal myelomeningocele has been a practice since 1994, with open repair techniques being used since 1997, indicating a long history of this intervention.

Despite extensive research on various aspects of this procedure, there are still unanswered questions regarding its implications for both mothers and babies that need to be addressed in public discussions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrauterine surgery in myelomeningocele. Bruner, JP.[2007]

Prenatal repair of myelomeningocele significantly reduced the need for cerebrospinal fluid shunts in infants, with only 40% requiring shunts compared to 82% in the postnatal repair group, indicating a relative risk reduction of 52%.

At 30 months, children who underwent prenatal surgery showed better mental development and motor function scores, although this approach also carried increased risks of preterm delivery and uterine complications for the mother.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of prenatal versus postnatal repair of myelomeningocele. Adzick, NS., Thom, EA., Spong, CY., et al.[2022]

The laparotomy-assisted 2-port fetoscopic technique for prenatal closure of spina bifida was successfully completed in 84% of cases, indicating its feasibility and effectiveness in a cohort of 19 women.

Postoperative improvements were observed in 86% of undelivered patients regarding hindbrain herniation, suggesting that this technique can lead to significant fetal health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation Process and Evolution of a Laparotomy-Assisted 2-Port Fetoscopic Spina Bifida Closure Program. Miller, JL., Groves, ML., Ahn, ES., et al.[2021]

In-utero surgical repair of fetal myelomeningocele can improve outcomes for affected infants, but it carries significant risks, as demonstrated by a case where the mother experienced complications like pulmonary edema and preterm labor after the procedure.

The infant delivered at 33 weeks after the surgery ultimately died from respiratory distress, highlighting the need for further well-controlled clinical trials to assess the safety and efficacy of this investigational technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lethal pulmonary hypoplasia after in-utero myelomeningocele repair. Lu, GC., Steinhauer, J., Ramsey, PS., et al.[2019]

In a study of 29 fetuses undergoing prenatal myelomeningocele repair, open surgery was linked to greater maternal hemodynamic changes and required higher doses of anesthetic agents compared to fetoscopic surgery.

Fetoscopic surgery resulted in fewer complications and less need for tocolytic drugs, suggesting it may be a safer option for mothers undergoing prenatal repair of neural tube defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study. Manrique, S., Maiz, N., García, I., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8192992/

Fetal myelomeningocele repair: a narrative review of the ... Evidence from this model suggested that in utero repair decreases the secondary damage to the exposed neural tissue and improves post-natal neurologic outcomes, ...

2. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/395270

In utero repair of myelomeningocele: Experimental ... Hypothesis Experimental work raises the possibility that in utero repair of myelomeningocele (mmc) may improve lower extremity, bladder, and bowel function, ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03090633

Fetoscopic Repair of Isolated Fetal Spina Bifida The purpose of this investigation is to evaluate maternal and fetal outcomes following fetoscopic repair of fetal spina bifida at the Johns Hopkins Hospital ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002937899701675

Endoscopic coverage of fetal myelomeningocele in utero Results: Four fetuses with open myelomeningocele underwent endoscopic coverage of the spinal lesion between 22 weeks 3 days and 24 weeks 3 days of gestation.

5. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1002/uog.20308

Proceedings of the First Annual Meeting of the International ... Fetoscopic in-utero spina bifida repair was introduced with the objective of reducing the maternal and fetal/neonatal complications/risks of ...

6. karger.com karger.com/fdt/article/52/5/521/927726/Safety-and-Effectiveness-of-Fetal-Myelomeningocele

Safety and Effectiveness of Fetal Myelomeningocele ... Conclusion: Exteriorized uterus fetoscopic repair of MMC proved safe for the mother and effective in closing the neural tube defect. It also ...

7. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/full/10.1002/uog.20308

Proceedings of the First Annual Meeting of the International ... Fetoscopic in-utero spina bifida repair was introduced with the objective of reducing the maternal and fetal/neonatal complications/risks of ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1744165X07000819

Intrauterine surgery in myelomeningocele Intrauterine surgery for repair of fetal myelomeningocele has been performed since 1994. Open repair through a hysterotomy has been performed since 1997.