Fetoscopic NEOX Cord 1K® Spina Bifida Repair

• ClinicalTrials.gov Identifier: NCT04243889
• Recruitment Status: Recruiting
• First Posted: January 28, 2020
• Last Update Posted: June 16, 2022
• Sponsor: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Ramesha Papanna, The University of Texas Health Science Center, Houston

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Spina Bifida; Myelomeningocele; Myeloschisis	Device: NEOX Cord 1K applied fetoscopically	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Fetoscopic Spina Bifida Repair Using a Cryopreserved Human Umbilical Cord Allograft (NEOX Cord 1K®) as a Meningeal Patch
• Actual Study Start Date: August 28, 2020
• Estimated Primary Completion Date: March 1, 2026
• Estimated Study Completion Date: February 28, 2031

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of patients with successful fetoscopic repair of the defect using NEOX Cord 1K® [ Time Frame: Immediately after repair procedure ]
   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.

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Ramesha Papanna, MD, MPH; (713) 500-6423; Ramesha.Papanna@uth.tmc.edu

Contact: Jeannine Garnett, PhD; (713) 486-6557; Jeannine.Garnett@uth.tmc.edu

Locations

United States, Texas

The University of Texas Health Science Center at Houston; Recruiting

Houston, Texas, United States, 77030

Contact: Ramesha Papanna, MD, MPH 713-500-6423 Ramesha.Papanna@uth.tmc.edu

Contact: Jeannine Garnett, PhD (713) 486-6557 Jeannine.Garnett@uth.tmc.edu

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Investigators

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

More Information

• Responsible Party: Ramesha Papanna, Associate Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT04243889
• Other Study ID Numbers: HSC-MS-19-1051
• First Posted: January 28, 2020
• Last Update Posted: June 16, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Ramesha Papanna, The University of Texas Health Science Center, Houston:

Neox Cord 1K; Fetoscopic repair; Cryopreserved human umbilical cord

Additional relevant MeSH terms:

Spinal Dysraphism; Meningomyelocele; Spina Bifida Cystica; Neural Tube Defects; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities