- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04652908
Cellular Therapy for In Utero Repair of Myelomeningocele - The CuRe Trial (CuRe)
Phase 1/2a Trial of Placental Mesenchymal Stem Cells for Repair of Fetal Myelomeningocele
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.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Maria G Hernandez, CPT1
- Phone Number: 916-734-4156
- Email: mghernandez@ucdavis.edu
Study Locations
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California
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Sacramento, California, United States, 95817
- Recruiting
- UC Davis Health
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Contact:
- Maria G Hernandez, CPT1
- Phone Number: 916-734-4156
- Email: mghernandez@ucdavis.edu
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Principal Investigator:
- Diana L Farmer, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
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;
Exclusion Criteria:
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment with PMSC-ECM
One-time administration of PMSC-ECM during the course of in utero fetal myelomeningocele surgery will be administered
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As in the current standard fetal surgery, under sonographic guidance, initial uterine entry will be accomplished by uterine stapling device or similar.
The fetus will be given an intramuscular injection of pain medications and paralytic.
The myelomeningocele will be closed in a standardized manner under magnification.
As in the standard fetal operation, the spinal cord will be dissected from surrounding tissue and allowed to drop into the spinal canal.
The PMSC-ECM product will then be tailored to the size of the spinal cord and applied topically, cell side down.
The PMSC-ECM product will be sutured in place to the dura.
Finally, the fetal skin will be closed in the standard fashion.
The amniotic fluid volume will be replaced and antibiotics will be added.
The uterus will be closed.
The abdominal fascial layer and skin will be closed in routine fashion.
Other Names:
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Other: non-PMSC untreated contemporaneous cohort
Contemporaneous cohort of patients undergoing routine fetal or postnatal MMC repair without PMSC-ECM (non-PMSC untreated contemporaneous cohort).
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The addition of a non-PMSC treated cohort, the untreated contemporaneous cohort, has been added at the request of the FDA to provide contemporaneous patients for validation of the continued relevance of use of the outcomes of the MOMS trial as the comparison arm for the Phase 2a portion of the study.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of the placenta-derived mesenchymal stem cell (PMSC-ECM) Product
Time Frame: Assessed at birth
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Will be assessed by evaluating the presence or absence of cerebrospinal fluid leak, infection at the MMC repair site, failure of the MMC repair site to heal, and any unexpected growths or tumor formation.
These will be assessed at birth by physical exam, brain and spinal ultrasound , and brain and spinal MRI.
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Assessed at birth
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of the PMSC-ECM Product
Time Frame: 30 months.
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This is primarily evaluated by improvement in motor function 2 or more levels greater than expected by anatomic level of the defect and by patients' ability to walk independently.
Bowel function will be assessed by caregiver questionnaires on bowel habits, and by anorectal manometry.
Urologic function will be assessed by caregiver questionnaires regarding urologic function, by renal and bladder ultrasounds to evaluate for hydronephrosis and bladder abnormalities, and by video urodynamics.
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30 months.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Diana L Farmer, MD, UC Davis School of Medicine
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1617774
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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