Neurofibromatosis Type ICOVANTTNCT02436746
The Cognitive Variability in NF1 and TSC Monozygotic Twins
An observational study of Neurofibromatosis Type I and Tuberous Sclerosis Complex, run by Erasmus Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Neurofibromatosis Type I, Tuberous Sclerosis Complex
- How many people
- 116 participants
- Where
- 1 siteNetherlands
- Study dates
- Apr 2015to Apr 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Monozygotic twin pairs with genetically confirmed Neurofibromatosis type I or Tuberous Sclerosis Complex
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus MC
Rotterdam, 3000 CA
Ype Elgersma, Prof., +31 10 7037739, y.elgersma@erasmusmc.nl
About this study
Official title: The Cognitive Variability in Neurofibromatosis Type I and Tuberous Sclerosis Complex Monozygotic Twins
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.
- Keywords
- Von Recklinghausen's disease, Bourneville's disease, Cognitive variability, Loss of heterozygosity
- Medical subject headings
- Neurofibromatosis 1, Tuberous Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Neurofibromatosis type I (NF1) | Monozygotic twin pairs with genetically confirmed Neurofibromatosis type I | |
| Tuberous Sclerosis Complex (TSC) | Monozygotic twin pairs with genetically confirmed Tuberous Sclerosis Complex |
What is being measured
The primary outcome is the main question the study is designed to answer.
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) )
Measured: 1 day
Secondary outcomes (6)
Correlation of word reading ability
One-minute word-reading test
Measured: 1 day
Correlation of attention problems
Conners ADHD rating scale
Measured: 1 day
Correlation of behavioural problems
Child Behaviour Checklist or Adult Behaviour Checklist (CBCL/ABCL)
Measured: 1 day
Correlation of autistic features
Social Responsiveness Scale (SRS)
Measured: 1 day
Correlation of visuospatial judgement (NF1 twins only)
Judgement of Line Orientation (JLO)
Measured: 1 day
Correlation of executive control (TSC twins only)
Trail-Making Test parts A \& B (TMT)
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2015 (estimated)
- Study startApr 2015
- Primary completionApr 2017 (estimated)
- Study completionApr 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurofibromatosis Type IStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M.C.Y. de Wit, MD PhD, Erasmus Medical Center
- Investigators
- Ype Elgersma, Prof., Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02436746
- Sponsor's protocol ID
- MEC-2014-483
- Acronym
- COVANTT
- Status last verified
- May 2015
- First submitted
- 29 Apr 2015
- Last updated
- 7 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Cognitive Variability in Neurofibromatosis Type I and Tuberous Sclerosis Complex Monozygotic Twins
- ClinicalTrials.gov ID
- NCT02436746
- Acronym / sponsor ID
- COVANTT / MEC-2014-483
- Keywords
- Von Recklinghausen's disease, Bourneville's disease, Cognitive variability, Loss of heterozygosity
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 116 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Apr 2017 (estimated)
- Study completion
- Apr 2017 (estimated)
- First posted
- 7 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neurofibromatosis type I (NF1) | – | –Monozygotic twin pairs with genetically confirmed Neurofibromatosis type I |
| Tuberous Sclerosis Complex (TSC) | – | –Monozygotic twin pairs with genetically confirmed Tuberous Sclerosis Complex |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Monozygotic twin pairs with genetically confirmed Neurofibromatosis type I or Tuberous Sclerosis Complex
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation of full intelligence quotient
Time frame: 1 day
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) )
6 secondary outcomes
Correlation of word reading ability
Time frame: 1 day
Correlation of attention problems
Time frame: 1 day
Correlation of behavioural problems
Time frame: 1 day
Correlation of autistic features
Time frame: 1 day
Correlation of visuospatial judgement (NF1 twins only)
Time frame: 1 day
Correlation of executive control (TSC twins only)
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ype Elgersma, Prof. principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neurofibromatosis Type I and Tuberous Sclerosis Complex, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ype Elgersma, Prof. (+31 10 7037739, y.elgersma@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of full intelligence quotient (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2015.