Congenital Cerebellar AtaxiasATAXICNCT01488461
Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias
An observational study of Congenital Cerebellar Ataxias and Early-onset Cerebellar Ataxias, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Congenital ataxias (CA) are rare, non progressive diseases, characterized by psychomotor retardation, hypotonia followed by ataxia. The presence of the "molar tooth" on MRI allowed to define Joubert syndrome, a peculiar form of CA. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Congenital Cerebellar Ataxias, Early-onset Cerebellar Ataxias
- What is being tested?
- blood sample
- How many people
- 165 participants
- Where
- 1 siteFrance
- Study dates
- Jan 2012to Oct 2014
- 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: All types
Who may be able to join
- Patient, child or adult, affected with a congenital or early-onset ataxia defined by:
- Neurological symptoms observed before age of 2 years.
- Non progressive cerebellar ataxia observed at the time of examination. Karyotype done or in progress
Who cannot join
- Metabolic disease
- Specific MRI malformations suggesting a peculiar entity : molar tooth (joubert syndrome), superior vermis dysplasia with cleft (Oligophrenin)
- Muscle weakness and elevated creatine phosphokinase (CPK)
- Clearly progressive ataxia.
- Absence of signature of the informed consent.
- Absence of affiliation to social security
Trial locations and contacts
1 site in 1 country.
About this study
Congenital ataxias (CA) are rare, non progressive diseases, characterized by psychomotor retardation, hypotonia followed by ataxia. The presence of the "molar tooth" on MRI allowed to define Joubert syndrome, a peculiar form of CA. Apart from this group, CA are mostly associated with cerebellar atrophy or hypoplasia without molar tooth on MRI. CA are a clinically as well as genetically heterogeneous group of diseases. Early-onset ataxias are progressive but may be difficult to distinguish from CA in the first years of the disease. To date, few genes responsible for CA have been identified: ABC7 (X-linked CA associated with sideroblastic anemia), SLC9A6 (X-linked CA associated with severe mental retardation, autism and epilepsy), GPR56 (CA associated with polymicrogyria), ATCAY (pure CA in Cayman isolate); the involvement of the ATCAY and ABC7 genes has never been assessed in a large cohort of CA patients.
Primary objective:
Read more
To assess the frequency of mutations of the ATCAY and ABC7 genes in patients affected with non Joubert congenital or early-onset ataxia.
Secondary objective:
To identify new loci and/or genes responsible for CA To further describe the clinical phenotype of the CA and to assess the frequency of the various clinical types (pure CA/CA associated with spasticity/ syndromic CA, congenital/early-onset CA, sporadic/familial CA).
To describe the clinical phenotype of CA related to mutations in one of analysed genes.
Read the detailed description
All patients will be examined by a geneticist or a neuropediatric. All clinical data will be collected.
Strategy of the molecular study :
- for all multiplex and consanguineous families a linkage analysis (loci ATCAY and ABC7 and others AC known genes) will be performed.
- For all sporadic patients as well as linked multiplex and consanguineous families : sequencing of all coding exons of the gene ATCAY and others AC known genes.
- For all sporadic male patients and linked families : sequencing of all coding exons of the gene ABC7.
- For all patients with suggestive features : sequencing of all coding exons of the gene GPR56, VLDLR, NHE6 or other candidate gene.
- In consanguineous families : linkage analysis using SNP-array and analysis of candidate genes present in the regions of extended homozygosity
- linkage analysis in dominant families and analysis of candidate genes in the linked regions.
- If a new AC locus is identified (using linkage or CGH array), this gene will be sequenced in all patients.
- Being tested
- blood sample
- Keywords
- Congenital cerebellar ataxias, Genetics, Gene ATCAY, Gene ABC7, Cerebellar atrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampleGenetic
Blood sample will be analysed in order to check presence or not of mutation in ABC7, SLC9A6, GPR56, ATCAY.
| Study group | Role | What they receive |
|---|---|---|
| patients ataxic | Not described Receives: Genetic: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of the patients with a mutation in one of the analysed genes.
Measured: 1 day
Secondary outcomes (2)
Percentage of patients with severe/moderate/mild/absent intellectual deficiency
Measured: 1 day
Percentage of patients with/without epilepsy/spasticity/extraneurological features and nature and frequency of MRI anomalies
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 posted8 Dec 2011 (estimated)
- Study startJan 2012
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Cerebellar AtaxiasStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Family based
- Enrolment
- 165 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lydie Burglen, PhD, Principal investigator, Assistance Publique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01488461
- Sponsor's protocol ID
- NI 08034
- Other IDs
- AOM 09178
- Acronym
- ATAXIC
- Status last verified
- Jun 2015
- First submitted
- 6 Dec 2011
- Last updated
- 15 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phenotypic and Genotypic Studies in Congenital and Early Onset Ataxias
- ClinicalTrials.gov ID
- NCT01488461
- Acronym / sponsor ID
- ATAXIC / NI 08034
- Keywords
- Congenital cerebellar ataxias, Genetics, Gene ATCAY, Gene ABC7, Cerebellar atrophy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 165 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 8 Dec 2011 (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.
Congenital ataxias (CA) are rare, non progressive diseases, characterized by psychomotor retardation, hypotonia followed by ataxia. The presence of the "molar tooth" on MRI allowed to define Joubert syndrome, a peculiar form of CA. Apart from this group, CA are mostly associated with cerebellar atrophy or hypoplasia without molar tooth on MRI. CA are a clinically as well as genetically heterogeneous group of diseases. Early-onset ataxias are progressive but may be difficult to distinguish from CA in the first years of the disease. To date, few genes responsible for CA have been identified: ABC7 (X-linked CA associated with sideroblastic anemia), SLC9A6 (X-linked CA associated with severe mental retardation, autism and epilepsy), GPR56 (CA associated with polymicrogyria), ATCAY (pure CA in Cayman isolate); the involvement of the ATCAY and ABC7 genes has never been assessed in a large cohort of CA patients.
Primary objective:
To assess the frequency of mutations of the ATCAY and ABC7 genes in patients affected with non Joubert congenital or early-onset ataxia.
Secondary objective:
To identify new loci and/or genes responsible for CA To further describe the clinical phenotype of the CA and to assess the frequency of the various clinical types (pure CA/CA associated with spasticity/ syndromic CA, congenital/early-onset CA, sporadic/familial CA).
To describe the clinical phenotype of CA related to mutations in one of analysed genes.
Detailed description
All patients will be examined by a geneticist or a neuropediatric. All clinical data will be collected.
Strategy of the molecular study :
- for all multiplex and consanguineous families a linkage analysis (loci ATCAY and ABC7 and others AC known genes) will be performed.
- For all sporadic patients as well as linked multiplex and consanguineous families : sequencing of all coding exons of the gene ATCAY and others AC known genes.
- For all sporadic male patients and linked families : sequencing of all coding exons of the gene ABC7.
- For all patients with suggestive features : sequencing of all coding exons of the gene GPR56, VLDLR, NHE6 or other candidate gene.
- In consanguineous families : linkage analysis using SNP-array and analysis of candidate genes present in the regions of extended homozygosity
- linkage analysis in dominant families and analysis of candidate genes in the linked regions.
- If a new AC locus is identified (using linkage or CGH array), this gene will be sequenced in all patients.
Study design
- Observational model
- Family based
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients ataxic | – | Genetic: blood sample |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All types
Key inclusion criteria (3 listed)
- Patient, child or adult, affected with a congenital or early-onset ataxia defined by:
- Neurological symptoms observed before age of 2 years.
- Non progressive cerebellar ataxia observed at the time of examination. Karyotype done or in progress
Key exclusion criteria (6 listed)
- Metabolic disease
- Specific MRI malformations suggesting a peculiar entity : molar tooth (joubert syndrome), superior vermis dysplasia with cleft (Oligophrenin)
- Muscle weakness and elevated creatine phosphokinase (CPK)
- Clearly progressive ataxia.
- Absence of signature of the informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sampleBlood sample will be analysed in order to check presence or not of mutation in ABC7, SLC9A6, GPR56, ATCAY. | Genetic | patients ataxic |
Primary outcome
Percentage of the patients with a mutation in one of the analysed genes.
Time frame: 1 day
2 secondary outcomes
Percentage of patients with severe/moderate/mild/absent intellectual deficiency
Time frame: 1 day
Percentage of patients with/without epilepsy/spasticity/extraneurological features and nature and frequency of MRI anomalies
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 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.
Lydie Burglen, PhD principal investigator
Assistance Publique
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 Congenital Cerebellar Ataxias and Early-onset Cerebellar Ataxias, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 3 inclusion and 6 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: finished, as of the sponsor's last update on 15 Jun 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 France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of the patients with a mutation in one of the analysed genes. (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 15 Jun 2015.