Summary

Location
at Sacramento, California
Dates
study started
estimated completion
Principal Investigator
by Diana L Farmer, MD

Description

Summary

Spina bifida, or myelomeningocele (MMC), is a disorder where the lower part of the spinal cord of the fetus is exposed, meaning there is no bone or skin covering it. This is dangerous because the spinal cord contains cells which control one's ability to move their legs and walk, and also to be able to urinate and have bowel movements normally. One of the current treatments for fetal MMC is to perform a surgery on the fetus before it is born which has many names including in utero surgery, prenatal surgery, or fetal surgery. This is a surgery that occurs inside the uterus (the womb) where the surgeon closes the opening in your fetus' back to cover the exposed spinal cord. Researchers have found that adding stem cells to the repair is effective in improving the ability of animals with MMC to walk, and that the stem cells are safe in animal studies. These stem cells are thought to protect the cells in the spinal cord that control movement and developmental outcomes. This study is being performed to look at the safety and effectiveness of stem cells on the fetus's exposed spinal cord during prenatal surgery.

Official Title

Phase 1/2a Trial of Placental Mesenchymal Stem Cells for Repair of Fetal Myelomeningocele

Details

Historically, treatment of MMC was limited to post-natal surgery to close the dura and skin over the spinal cord to prevent meningitis, which had no effect on motor function. The potential benefit of earlier intervention was realized when prenatal ultrasound of patients with MMC early in gestation revealed near-normal leg movements despite displaying paralysis at birth. This finding gave credence to the two-hit hypothesis that paralysis was progressive during prenatal life and suggested that fetal intervention could prevent the secondary damage to the spinal cord. Fetal repair of MMC did confer improvement in motor function of children treated in the Management of Myelomeningocele (MOMS) randomized controlled trial. The promising results of the MOMS trial demonstrated the potential for improvement of paralysis for these patients, but distal motor function still remained severely impaired in the majority of patients with MMC with standard in utero repair alone. While this demonstrated that the ideal time to intervene to prevent paralysis is in utero with the goal of preventing the accrual of ongoing damage to the spinal cord, there is still room for improvement. The remarkable regenerative capacity of the fetal environment combined with regenerative capacity of placental mesenchymal stem cells offers potential for augmentation of the fetal repair of MMC with a novel therapy to further reduce and repair the sustained spinal cord damage.

Keywords

Myelomeningocele Meningomyelocele Spina Bifida Cystica Placental Mesenchymal Stem Cells seeded on a commercially available dural graft extracellular matrix Untreated contemporaneous cohort

Eligibility

You can join if…

Eligibility for fetal surgery per the MOMS trial, which are:

  • Myelomeningocele (including myeloschisis) at any level from T1 through S1 with hindbrain herniation. Lesion level will be confirmed by ultrasound and hindbrain herniation will be confirmed by MRI at the UC Davis Fetal Center
  • Maternal age ≥18 years
  • Gestational age at enrollment between 19 weeks 0 days and 25 weeks 6 days gestation as determined by clinical information and evaluation of first ultrasound
  • Normal karyotype. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is greater than 24 weeks gestation;

You CAN'T join if...

Not being eligible for fetal surgery per the MOMS trial, which includes:

  • Multifetal pregnancy
  • Insulin dependent pregestational diabetes
  • Fetal anomaly not related to myelomeningocele.
  • Kyphosis in the fetus of 30 degrees or more
  • Current or planned cerclage or documented history of incompetent cervix, placenta previa or placental abruption
  • Short cervix < 20 mm measured by cervical ultrasound
  • Obesity as defined by body mass index of 35 or greater
  • Previous spontaneous singleton delivery prior to 37 weeks
  • Maternal-fetal Rh isoimmunization, Kell sensitization or a history of neonatal alloimmune thrombocytopenia
  • Maternal HIV or Hepatitis-B status positive due to 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
  • Known Hepatitis-C positivity. If the patient's Hepatitis C status is unknown, she does not need to be screened
  • Uterine anomaly such as large or multiple fibroids or Müllerian duct abnormality
  • Other maternal medical condition which is a contraindication to surgery or general anesthesia. This includes any patient with a previous hysterotomy in the active segment of the uterus (whether from a previous classical cesarean, uterine anomaly such as an arcuate or bicornuate uterus, major myomectomy resection, or previous fetal surgery)
  • Patient does not have a support person (e.g., husband, partner, mother)
  • Inability to comply with the travel and follow-up requirements of fetal surgery
  • Patient does not meet other psychosocial criteria (as determined by the psychosocial interviewer) to handle the implications of fetal surgery
  • Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy;
  • Maternal hypertension 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)
  • Active COVID-19 infection at time of fetal surgery as determined by positive test

Location

  • UC Davis Health accepting new patients
    Sacramento California 95817 United States

Lead Scientist at UC Davis

  • Diana L Farmer, MD
    Professor, Surgery. Authored (or co-authored) 215 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Diana Lee Farmer
Links
Sign up for this study
ID
NCT04652908
Phase
Phase 1/2
Study Type
Interventional
Last Updated