Effects of a Multiple Sclerosis Relapse Therapy on Offspring Neurocognitive Development and Behaviour

NCT04832269 | Recruiting

• 1 other identifier: ZKSJ0130
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Introduction: Fetal exposure to glucocorticoids (GCs) used to induce fetal lung maturation in women threatened by premature labour is known to induce aberrations in brain development and stress sensitivity, cognitive dysfunction and neuro-psychiatric disorders in later life which all predict early brain ageing. Another common source of fetal GC exposure is the treatment of relapses in multiple sclerosis (MS), the most common neurological disease in young women. Despite the lack of studies, the 300-fold higher dosage of GCs for MS relapse treatment compared to obstetric indications is considered harmless for the fetus . Objectives: To examine the effects of GCs for MS relapse treatment during pregnancy on offspring structural and functional brain development, stress sensitivity, and cognitive and behavioural performance. Methods: Epidemiological multi-centre cohort study in 80 children and adolescents aged 8 to 18 years whose mothers received GCs to treat a MS relapse during pregnancy compared to unexposed participants. Expected Impact: Creating a guideline-changing evidence-based risk-benefit assessment regarding benefits of the MS relapse therapy for the mother and potential harm to the child.

Conditions

Multiple Sclerosis

Keywords

fetal programming; pregnancy; relapse therapy

Outcome Measures

Primary Outcomes (1)

• General cognitive ability - Reynolds Intellectual Assessment Scales and Screening (RIAS)

  Intelligence quotient as measured by RIAS, higher scores denote better outcome.

  approx. 30 - 40 min.

Secondary Outcomes (12)

• Structural brain development - BrainAge score

  approx. 20 min.

• Salivary cortisol decay curve

  approx. 5 min. per swab

• Salivary alpha-amylase

  approx. 5 min. per swab

• Heart rate variability

  approx. 75 min.

• Spectral edge frequency in the EEG

  approx. 75 min.

Other Outcomes (1)

• Methylation of GR-receptor gene

  approx. 10 min.

Study Arms (2)

MP exposed group

children and adolescents (aged 8 to 18 years) of mothers with prenatal exposition to MP in the context of an MS relapse therapy

Other: Exposure to methylprednisolone during pregnancy

MP non-exposed group/control group

children and adolescents of mothers suffering from MS aged 8 to 18 years

Interventions

Exposure to methylprednisolone during pregnancy OTHER

Exposure to methylprednisolone during pregnancy in the context of an MS relapse therapy

MP exposed group

Eligibility Criteria

• Age: 8 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The study population is composed of children aged 8 to 18 from mothers with multiple sclerosis who received methylprednisolone in pregnancy and children aged 8 to 18 from mothers with multiple sclerosis without methylprednisolone therapy during pregnancy

You may qualify if:

• MS diagnosis was made based on the McDonald criteria valid at the time of diagnosis
• Written consent by the legal guardians of the participating child following a detailed oral and written education
• Exposed group (n=40): Children and adolescents (aged 8 to 18 years) of mothers with prenatal exposition to MP in the context of a MS relapse therapy
• Non-exposed group (n=40): Children and adolescents of mothers suffering from MS without MP therapy during pregnancy (aged 8 to 18 years) matched for age, gender and social background

You may not qualify if:

• Perinatal complications such as cerebral bleeding, neonatal intensive care with ventilation, prenatal therapy with glucocorticoids except for an MS relapse
• Maternal abuse of noxious agents during pregnancy
• Long-term glucocorticoid medication (e.g. asthma)
• Preterm births (before 36 weeks of pregnancy)
• Severe disease making an examination impossible (e.g. mental retardation)
• disease-modifying therapy during pregnancy

Sponsors & Collaborators

• Jena University Hospital: lead
• Ruhr University of Bochum: collaborator
• Interdisciplinary Center of Clinical Research of the Medical Faculty Jena: collaborator
• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (2)

Ruhr University of Bochum

Bochum, 44791, Germany

RECRUITING

University Hospital Jena

Jena, 07747, Germany

RECRUITING

Related Publications (23)

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  BACKGROUND

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  BACKGROUND

• Kozik V, Schwab M, Thiel S, Hellwig K, Rakers F, Dreiling M. Protocol for a Cross-Sectional Study: Effects of a Multiple Sclerosis Relapse Therapy With Methylprednisolone on Offspring Neurocognitive Development and Behavior (MS-Children). Front Neurol. 2022 Apr 26;13:830057. doi: 10.3389/fneur.2022.830057. eCollection 2022.

  PMID: 35557615 DERIVED

Related Links

• Official web page providing study information

Biospecimen

Retention: SAMPLES WITH DNA

GC receptor sensitivity, methylation of the GR-receptor gene

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Florian Rakers

  University Hospital Jena

  PRINCIPAL INVESTIGATOR

• Matthias Schwab, Prof. Dr.

  University Hospital Jena

  STUDY DIRECTOR

Central Study Contacts

Michelle Dreiling, Dr.

CONTACT

+493641 9 32 35 93; michelle.dreiling@med.uni-jena.de

Florian Rakers, PD Dr.

CONTACT

+493641 9 32 34 67; florian.rakers@med.uni-jena.de

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: April 5, 2021
• Study Start: October 19, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)