Fetoscopic NEOX Cord 1K® Spina Bifida Repair

Fetoscopic Spina Bifida Repair Using a Cryopreserved Human Umbilical Cord Allograft (NEOX Cord 1K®) as a Meningeal Patch

To fetoscopically use cryopreserved human umbilical cord allografts, named NEOX Cord 1K®, as a spinal cord cover of spina bifida defects. This procedure will be performed to create a watertight seal covering over the spinal cord in order to decrease the incidence rates of postnatal morbidities. For larger skin defects, NEOX Cord 1K® may be used as a skin cover.

Study Overview

• Status: Recruiting
• Conditions: Myelomeningocele; Spina Bifida; Myeloschisis
• Intervention / Treatment: Device: NEOX Cord 1K applied fetoscopically

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ramesha Papanna, MD, MPH; Phone Number: (713) 500-6423; Email: Ramesha.Papanna@uth.tmc.edu
• Study Contact Backup: Name: Jeannine Garnett, PhD; Phone Number: (713) 486-6557; Email: Jeannine.Garnett@uth.tmc.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas Health Science Center at Houston
      • Contact: Jeannine Garnett, PhD; Phone Number: (713) 486-6557; Email: Jeannine.Garnett@uth.tmc.edu
      • Contact: Ramesha Papanna, MD, MPH; Phone Number: 713-500-6423; Email: Ramesha.Papanna@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Maternal inclusion criteria:

• Singleton pregnancy
• Gestational age at screening is 19 to 25 5/7 weeks and gestational age at surgery is 22 to 25 6/7 weeks
• Maternal age: 18 years and older
• Body mass index < 40 kg/m2
• No preterm birth risk factors (short cervix, history of previous preterm delivery)
• No previous uterine incision in the active uterine segment
• Willing to undergo an open fetal repair if the fetoscopic approach is unsuccessful

Fetal inclusion criteria:

• Spina bifida defect between T1 to S1 vertebral levels
• Chiari II malformation
• No evidence of kyphosis (curved spine)
• No major life-threatening fetal anomaly unrelated to spina bifida
• Normal karyotype, or normal CMA, or a CMA with variants of unknown significance

Exclusion Criteria:

Maternal exclusion criteria:

• Non-resident of the United States
• Multifetal pregnancy
• Poorly controlled insulin-dependent pregestational diabetes
• Poorly controlled A2DM insulin-dependent diabetes
• Current or planned cerclage or documented history of an incompetent cervix
• Placenta previa or placental abruption
• Short cervix of < 20 mm
• Obesity as defined by a body mass index of > 40 kg/m2
• Previous spontaneous singleton delivery prior to 37 weeks
• Maternal-fetal Rh isoimmunization, Kell sensitization, or a history of neonatal alloimmune thrombocytopenia
• HIV or Hepatitis-B positive status
• Known Hepatitis-C positivity
• Uterine anomaly such as large or multiple fibroids or a mullerian duct abnormality that is diagnosed via imaging prior to surgery, which that are unavoidable during surgery
• Other medical conditions which are contraindication to surgery or general anesthesia
• Patient does not have a support person
• Inability to comply with the travel and follow-up requirements of the trial
• Patient does not meet psychosocial standardized assessment criteria
• Participation in this or another intervention study that influences maternal and fetal morbidity and mortality
• Maternal hypertension
• Zika virus positivity
• Allergy/history of drug reaction to Amphotericin B

Fetal exclusion criteria:

• Major fetal anomaly not related to spina bifida
• Kyphosis in the fetus of 30 degrees or more
• Ventriculomegaly greater than 15 mm and no movements noted at hip and knee joints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NEOX Cord 1K applied fetoscopically; Patients intending to undergo open in-utero spina bifida repair, will be offered to be screened for an alternative minimally invasive approach. All eligible pregnant mothers' fetuses within the trial will receive NEOX Cord 1K® as a spinal cord cover to close the developmental defect. In some cases, at the discretion of the Neurosurgeon, NEOX Cord 1K® may be required to cover the skin. All eligible subjects meeting all inclusion criteria but none of the exclusion criteria may be enrolled.

Device: NEOX Cord 1K applied fetoscopically; Under general anesthesia and tocolysis, in-utero repair begins with a laparotomy that is followed by exteriorization of the uterus. The fetus is then positioned by external cephalic version. Uterine entry will be accessed using 3 cannulas, followed by heated-humidified carbon dioxide insufflation for visualization. Then, fetoscopically the placode will be examined and dissected. The lesion will be repaired using NEOX Cord 1K® (HUC) for closure of the first layer over the neural placode. Primary closure of the skin will then occur, or NEOX Cord 1K® (HUC) will be used for skin closure at the discretion of the neurosurgeon. Finally, the laparotomy site will be sutured in multiple layers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with successful fetoscopic repair of the defect using NEOX Cord 1K®	A digital image of the fetal repair site will be captured during and immediately after the repair. The images will be sent to three independent blinded neurosurgeons for review of successful closure of the defect. More than best of three votes will be considered as the result.	Immediately after repair procedure

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with intact repair of the defect, defined as no cerebrospinal fluid leakage and no dehiscence at the repair site.	Birth
Number of patients with intact repair of the defect as defined as no cerebrospinal fluid leakage and no dehiscence at the repair site.	12 months ± 2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Arnold-Chiari malformation II	Assessment of Arnold-Chiari malformation II as measured by MRI of head	birth discharge or 1 month + 30 days, 12 ± 2 months, and 60-66 months post birth
Number of patients with absence of brain stem kinking as assessed by MRI evaluation.		birth-discharge or 1 month + 30 days, 12 ± 2 months, and 60-66 months post birth
Number of patients with lower extremity motor and sensory levels exceeding the anatomical level of the lesion by ≥ 2 segments.		2 ± 2 months, 30-36 months and 60-66 months post birth
Number of patients who can ambulate with or without the use of orthotics or devices.		12 ± 2 months, 30-36 months and 60-66 months post birth
Number of patients with no spinal cord tethering as assessed by a lumbar spine MRI.		birth-discharge or 1 month + 30 days, 12 ± 2 months, and 60-66 months post birth
Number of patients with absence of syringomyelia as assessed by an MRI.		12 ± 2 months post birth
Number of patient with the absence of an epidermoid cyst at the repair site, determined by MRI.		birth-discharge or 1 month + 30 days, 12 ± 2 months, and 60-66 months post birth
Number of patients needing de-tethering surgery before the 12 month ± 2 month visit as clinically indicated.		12 ± 2 months
Developmental motor scales as assessed by the Bayley IV test.		30-36 months follow up post birth
Adaptive behavior as assessed by the Vineland Adaptive Behavior Scales III		30-36 months and 60-66 months post delivery
Achievement as measured by the Woodcock-Johnson IV Test of Achievement test		60-66 months post birth
Assess brain stem function, as measured by the child's swallowing profile		12 ± 2 months; 30-36 months and 60-66 months post birth
Urodynamic function assessments	Objective measures of the function of the lower urinary tract by evaluating post-void residual urine	12 ± 2 months, 30-36 months and 60-66 months post birth
Bowel function assessments bowel movements.	Bowel function as assessed by observation of neurogenic bowel incontinence or constipation	12 ± 2 months, 30-36 months and 60-66 months post birth
Verbal and non-verbal intelligence as measured by the Kaufman Brief Intelligence Test 2 (KBIT-2)		60-66 months post delivery
Manual dexterity and bimanual coordination as determined by the Purdue Pegboard test		60-66 months post delivery
Executive function testing as measured by the Behavior Rating Inventory of Executive Function 2 (BRIEF2) test		60-66 months post delivery
Visual motor integration as assessed by the Beery Visual-Motor Integration test		60-66 months post delivery
Quality of Life as assessed by the Parkin Spina Bifida Health-Related Quality of Life questionnaire		60-66 months post delivery

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Ramesha Papanna, MD, MPH, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Anticipated): March 1, 2026
• Study Completion (Anticipated): February 28, 2031

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 24, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 16, 2022
• Last Update Submitted That Met QC Criteria: June 14, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Neox Cord 1K; Fetoscopic repair; Cryopreserved human umbilical cord
• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Nervous System Malformations; Neural Tube Defects; Meningomyelocele; Spina Bifida Cystica; Spinal Dysraphism
• Other Study ID Numbers: HSC-MS-19-1051

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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