The Cognitive Variability in NF1 and TSC Monozygotic Twins

Tuberous Sclerosis Complex Clinical Trial

— COVANTT  

Official title:

The Cognitive Variability in Neurofibromatosis Type I and Tuberous Sclerosis Complex Monozygotic Twins

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02436746
• Other study ID #: MEC-2014-483
• Status: Recruiting
• Phase: N/A
• First received: April 29, 2015
• Last updated: May 4, 2015
• Start date: April 2015
• Est. completion date: April 2017

Study information

• Verified date: May 2015
• Source: Erasmus Medical Center
• Contact: Ype Elgersma, Prof.
• Phone: +31 10 7037739
• Email: y.elgersma[@]erasmusmc.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial Summary

Both Neurofibromatosis type 1 (NF1) and Tuberous Sclerosis Complex (TSC) are highly heterogeneous diseases. Cognitive features seem to vary widely even between family members carrying the same mutation. This phenotypic variability is not well understood, but is generally assumed to be caused by modifier genes which regulate the affected pathways. However, recent studies brought forward an alternative explanation for the phenotypic variability. Post-mortem studies showed that second hit mutations causing loss of the second ('healthy') allele are more widespread than previously believed. These loss of heterozygosity (LOH) mutations cause bi-allelic loss of the disease-linked gene and are known to cause the gross of somatic features in both diseases (like neurofibromas and hamartomas). Hence, it could be the stochastic occurrence of second-hit mutations in the brain are the cause of the variable cognitive phenotypes.

To investigate to what extent these LOH mutations in the brain contribute to the phenotype and to what extent this variation is due to genetic modifiers factors is unknown. The investigators therefore propose to elucidate this variability by comparing the correlation of cognitive features of monozygotic twins with NF1 or TSC to healthy twins in the population. If modifier genes are the cause of the variability of cognitive features in NF1 and TSC the investigators expect that the variability in cognitive tests in monozygotic twins is the same as monozygotic twins in the healthy population. However, if the variability is caused by the occurrence of LOH mutations, the investigators expect to have a lower correlation in our monozygotic patients compared to the healthy twins.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• The participant is part of a monozygotic twin pair (which is genetically confirmed);

• NF1 or TSC patients with a genetically confirmed diagnosis;

• Oral and written informed consent by participant in case = 18 years of age.

• Oral and written informed consent by both caregivers and assent by participant in case of minor participants.

Exclusion Criteria:

• A potential subject of whom the twin sibling is not willing or able to participate in this study, will be excluded from participation in this study.

• Symptomatic brain pathology.

Study Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis Type I
• Sclerosis
• Tuberous Sclerosis
• Tuberous Sclerosis Complex

Locations

Country	Name	City	State
Netherlands	Erasmus MC	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of full intelligence quotient	Depending on age and cognitive development: Bayley Scales of Infant Development (BSID-III) or Wechsler Scale of Intelligence (Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) or Wechsler Intelligence Scale for Children (WISC-III) or Wechsler Adult Intelligence Scale (WAIS-III) )	1 day	No
Secondary	Correlation of word reading ability	One-minute word-reading test	1 day	No
Secondary	Correlation of attention problems	Conners ADHD rating scale	1 day	No
Secondary	Correlation of behavioural problems	Child Behaviour Checklist or Adult Behaviour Checklist (CBCL/ABCL)	1 day	No
Secondary	Correlation of autistic features	Social Responsiveness Scale (SRS)	1 day	No
Secondary	Correlation of visuospatial judgement (NF1 twins only)	Judgement of Line Orientation (JLO)	1 day	No
Secondary	Correlation of executive control (TSC twins only)	Trail-Making Test parts A & B (TMT)	1 day	No

External Links

•   ENCORE - Expertisecenter for NeuroCognitive Developmental Disorders