Cellular Therapy for In Utero Repair of Myelomeningocele - The CuRe Trial

ConditionMyelomeningocele

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age19-25

SponsorUniversity of California, Davis

About this trial

Spina bifida, or myelomeningocele (MMC), is a birth defect that results in paralysis, excess fluid on the brain (hydrocephalus), and impaired ability to urinate and have bowel movements normally. In a previous study (the MOMS trial), surgery before birth (in-utero/fetal surgery) was shown to reduce the need for shunting for hydrocephalus. There was also some improvement in ambulation, but 58 % of the children still could not walk unassisted.

This study is testing living stem cells from placenta added to the fetal repair in an effort to improve the ability to walk. Previous animal studies have shown dramatic improvement in walking and bowel and bladder function when placental stem cells are added to MMC repair. Use of these "living" cells may protect the developing spinal cord, prevent further injury, and may even reverse existing damage to the nerves that control movement. This study is assessing the safety and efficacy of adding stem cells to open fetal surgery for MMC in humans.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

Multifetal pregnancy

Insulin dependent pregestational diabetes

Fetal anomaly not related to myelomeningocele.

Kyphosis in the fetus of 30 degrees or more

Trial design

Design model

Parallel

Treatments tested in this trial

Placental Mesenchymal Stem Cells seeded on a commercially available dural graft extracellular matrix
Biological/Vaccine
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.
Untreated contemporaneous cohort
Other intervention
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.

Treatment groups

55 Participants

are divided into 2 treatment groups

Group A: Treatment with PMSC-ECMExperimental treatment 1 intervention

Group B: non-PMSC untreated contemporaneous cohortOther 1 intervention

Trial outcomes

Primary outcomes

Safety of the placenta-derived mesenchymal stem cell (PMSC-ECM) Product

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.

Time frame

Assessed at birth

Secondary outcomes

Efficacy of the PMSC-ECM Product

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.

Time frame

30 months.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of California, Davis

Lead sponsor

California Institute for Regenerative Medicine (CIRM)

Collaborator

Source ClinicalTrials.gov

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