The Biomarkers of Neurological Disease in Utero Study

NCT04043572 | Unknown

• 1 other identifier: 19OB002
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Anti-epileptic drugs (AEDs) are potent teratogens associated with a spectrum of physical and neurodevelopmental anomalies to the exposed fetus. Particular risks include congenital malformations, impaired motor and cognitive functioning, autism and poorer educational attainment. Fetal exposure to drugs that bind to central nervous system targets as part of their therapeutic effect (e.g. neurotransmitter receptors and neuronal channels) appear to alter brain structure and function in both animal models and humans. Fetal magnetic resonance imaging offers an approach to investigate these effects in vivo, identifying biomarkers, defining the onset of abnormalities and dose response. Fetal MRI may offer risk stratification and identify patients that may benefit from intervention early in development. The overall aim of this study is to contribute to improving developmental outcomes following the inevitable exposure during treatment of maternal epilepsy. This novel study aims to explore the central nervous system with state-of-the-art non-invasive multimodal magnetic resonance imaging consistent with the University of Nottingham Precision Imaging Beacon, so as to improve outcomes in patients at risk of long term complex neuropsychiatric conditions.

Conditions

Epilepsy; Neurodevelopmental Disorders; Fetal Disease; Teratogenesis

Keywords

Fetus; Neurological Development; Teratogenicity; Anti-Epileptic Drugs; Epilepsy

Outcome Measures

Primary Outcomes (4)

• Using in utero MRI, can we detect abnormal structural brain development in fetuses exposed to anti-epileptic drugs compared to healthy controls.

  To use volume reconstructed MRI data to measure volumetric changes (in mm cubed) in brain parenchyma substructures in cases of anti-epileptic drug exposed and healthy fetuses.

  60 months

• Using in utero diffusion MRI, can we detect abnormal brain connectivity in fetuses exposed to anti-epileptic drugs compared to healthy controls.

  To use motion-corrected diffusion MRI data to assess white matter connectivity as determined by changes in fractional anisotropy, apparent diffusion coefficient, and tractography.

  60 months

• Using in utero functional MRI, can we detect abnormal brain blood-oxygen (BOLD) dependant signal in fetuses exposed to anti-epileptic drugs compared to healthy controls.

  To use motion-correct functional MRI to determine changes in the resting state network as determined by measuring BOLD signal activation.

  60 months

• Using in utero cine MRI, can we detect abnormal motor behaviour in fetuses exposed to anti-epileptic drugs compared to healthy controls.

  To use General Movement analysis to detect abnormal patterns of motor behaviour in fetuses as compared to healthy controls.

  60 months

Study Arms (2)

Participants with Epilepsy

This group comprises pregnant patients with epilepsy who are actively using anti-epileptic drugs

Healthy Controls

Healthy volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The cases will be selected from the joint epilepsy-obstetrics clinical service.

You may qualify if:

• Singleton pregnancy Age 18 - 45 years BMI \< 50 Able to give informed consent

You may not qualify if:

• Multiple pregnancy Age less than 18 or greater than 45 years old BMI \> 50 Unable to give informed consent Contraindication to MRI Refractory seizures Seizure(s) within last 30 days Unstable for transfer to MRI

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead
• University of Nottingham: collaborator

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Epilepsy; Neurodevelopmental Disorders; Fetal Diseases; Teratogenesis

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tayyib T Hayat, MRCP PhD

  Nottingham University Hospitals NHS Trust

  STUDY CHAIR

Central Study Contacts

Tayyib T Hayat, MRCP PhD

CONTACT

+447971903513; tayyib.hayat@nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: August 2, 2019
• Study Start: June 1, 2019
• Primary Completion: September 1, 2025
• Study Completion: October 1, 2025
• Last Updated: October 8, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)