SchizophreniaGenAuDissNCT02565524
the Phenotypic and Genetic Profile of Patients With Early Onset Schizophrenia Associated With Autism Spectrum Disorder.
A study testing genetic and phenotypic profile in people with Schizophrenia and Dissociative Disorders, run by Fondation Lenval at 1 site in France.
Trial summary
Early onset schizophrenia "early dissociative disorder" is a rare disorder with a low incidence of approximately (1/5000 to 1/20000). Its link with autism spectrum disorders remains unknown although both are serious neurodevelopmental diseases. Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Schizophrenia, Dissociative Disorders
- What is being tested?
- genetic and phenotypic profile
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 1 siteFrance
- Study dates
- 18 May 2014to 30 May 2023
- Phase
- Interventional
- 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 7 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Of the child:
- ≥ 7 years, <18 (below 7 years the diagnosis of schizophrenia is not possible)
- Schizophrenia Diagnosis done using the diagnostic tool Kiddie sads
- Autism Diagnosis done using the diagnostic scale Autism Diagnostic interview (ADI-R)
- Intelligence quotient (IQ) ≥ 50 at Wechsler Intelligence Scale for Children (WISC) IV abridged version
- Clinical examination
Show all 19Show fewer
- Affiliation to social security
- Obtaining the authorization of the holders of parental authority
- Brothers and sisters:
- Minor or Major
- Similarly biological parents
- Clinical examination
- Affiliation to social security
- Obtaining the authorization of the holders of parental authority for minors or informed consent for major
- Parents:
- Biological Parent
- Clinical examination
- Affiliation to social security
- Informed Consent
Who cannot join
- Of the child:
- Children refusing to participate
- Children without verbal language
- Brothers and sisters:
- Children refusing to participate
- Adults protected by law
Show all 9Show fewer
- Parents:
- Refusing to participate
- Adults are protected by law
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploration and Characterization of the Phenotypic and Genetic Profile of Patients With Early Onset Schizophrenia Associated With Autism Spectrum Disorder and Their First-degree Relatives (GenAuDiss).
Early onset schizophrenia "early dissociative disorder" is a rare disorder with a low incidence of approximately (1/5000 to 1/20000). Its link with autism spectrum disorders remains unknown although both are serious neurodevelopmental diseases. As part of the 2011-2013 Interregional hospital Clinical Research program, University Department of Child and Adolescent Psychiatry Pediatric Hospitals of CHU de Nice Lenval identified patients with a complex phenotype characterized by an early schizophrenia associated with autism spectrum disorders and developmental disabilities in mild to moderate. This phenotype could be a new syndrome.
The goal of our project is to define the genetic causes of this phenotype. The technique of high throughput sequencing will be used to obtain the sequence of exomes of these patients and their families. This study will therefore be important to give an accurate diagnosis for patients and their families. Moreover, we believe that this project will identify new genes involved allowing a better understanding of the pathophysiology. Recent studies show the involvement of mutations in several genes (eg NRXN1 and UPF3B) in these different clinical phenotypes. However, the genetic basis of the childhood and early onset schizophrenia are much less well known than those of autism spectrum disorder
Read the detailed description
Introduction: Early-onset Schizophrenia (EOS) is a rare and severe condition displaying early dissociative disorder (i.e., age of onset < 18 years). A higher rate of neurodevelopmental abnormalities is observed in EOS compared to adult onset schizophrenia (AOS). Thus, patients affected by EOS typically present intellectual, learning, communication or neuromotor impairments, as well as attention deficit hyperactivity disorder. Early signs of autism spectrum disorders (ASD) are also found in 30% of patients with EOS.
Cytogenetics abnormalities, including copy number variations (CNVs), are frequent in neurodevelopmental disorders and have been linked to ASD physiopathology. Implicated genes encode proteins playing a role in brain development, synaptic morphology, plasticity and neurogenesis. In addition, an increasing number of genetic abnormalities are shared by EOS and ASD, suggesting that schizophrenia can be considered a neurodevelopmental disorder.
The main objective of the present study is to identify mutations in genes involved in neurodevelopmental pathways in our cohort of patients affected by both EOS and ASD.
Method and analysis: We describe here a multicenter study in a pediatric population named "Exploration and characterization of genetic and phenotypic profile of the 'early dissociative disorder' associated with autism spectrum disorder (GenAuDiss)". The study started in April 2014. The inclusion criteria are: age 7 to 22 years, diagnoses of EOS with co-morbid ASD and IQ > 50; as well as parents and siblings of the included patients.
We perform standardized psychiatric assessments (MINI, K-SADS-PL, PANSS, SANS, TCI 226, and AQ) and neurocognitive evaluations (IQ, TMT A/B, and verbal fluency). Then, we study variants of the coding part of the DNA (exome), using next generation sequencing (NGS) process on trio (mother, father, and child). Divers bio-informatics tools such as RVIS and PolyPhen-2 will be used to prioritize the potential candidate genes. The inclusion period of this study will end in November 2019.
Ethics and dissemination: The study protocol was approved by the Ethics Committee 'Sud Méditerrané V' (number 14.002) and by the French National Agency for Medicines and Health Products Safety (ANSM 2013-A01699-36). All patients, their parents and siblings signed informed consent upon enrolment in the study.
Results of the present study should help to unravel the molecular pathology of EOS, paving the way for an early therapeutic intervention
- Conditions
- Schizophrenia, Dissociative Disorders
- Being tested
- genetic and phenotypic profile
- Keywords
- schizophrenia, early dissociative disorder, genetic
- Medical subject headings
- Schizophrenia, Dissociative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
genetic and phenotypic profileOther
Genetic and phenotypic profile, clinical and neurocognitive assessment for child with Schizophrenia and autism, their parents and brotherhood
| Study group | Role | What they receive |
|---|---|---|
| genetic and phenotypic profile | Experimental | blood sample, clinical and neurocognitive assessment Receives: Other: genetic and phenotypic profile |
What is being measured
The primary outcome is the main question the study is designed to answer.
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing standard karyotype
A standard karyotype at a resolution of 300 to 400 bands per haploid lot. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions.
A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions Big.
The pathological nature of these mutations will be stutied on the gene function and reaches its pattern of expression.
Measured: inclusion visit
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing search CGG
A search of the CGG expansion hypermethylated in the 5 'UTR of the FMR1 gene mutation that causes Fragile X syndrome.
Measured: inclusion visit
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing whole exome sequencing
Whole Exome Sequencing on trio (mother, father and child); This technology has demonstrated its power in recent years to determine the genetic causes of many rare diseases (Ropers, HH., 2012).
Measured: inclusion visit
Secondary outcomes (6)
Intensity of positive symptoms of schizophrenia
Evaluation of the intensity of positive and negative symptoms, general psychopathology and subtypes of schizophrenia by using positive and negative syndrome scale (PANSS)
Measured: inclusion visit
Co-morbid psychiatric diagnosis
Evaluation of clinical profile: by using K-SADS-PL scale for DSM IV-TR / DSM-5 co-morbid psychiatric diagnosis of patients and minor siblings and by using MINI assessments for DSM IV-TR / DSM 5 psychiatric diagnosis of parents and major siblings.
Measured: inclusion visit
Evaluation of executive and attentional by the verbal fluency test
Evaluation of executive and attentional functions of patients using Trail Making Test (TMT) A and B and verbal fluency;
Measured: inclusion visit
Clinical evaluation of autistic symptoms
Clinical evaluation of autistic symptoms by using AQ (Baron-Cohen) in siblings and parents
Measured: inclusion visit
Neurocognitive profile
Evaluation of cognitive functioning by Wechsler Intelligence Scale for Children Scale IV (WISC IV).full version in patient and WISC IV abridged version in minor siblings; Wechsler Adult Intelligence Scale-III (WAIS III) in a short form in adult siblings and parents
Measured: inclusion visit
Personality dimensional test
Personality dimensional test using computerized version of TCI 226 (Cloninger) in parents
Measured: inclusion visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2015 (estimated)
- Study start18 May 2014
- Primary completion30 May 2023
- Study completion30 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fondation Lenval
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emmanuelle DOR, MD, Principal investigator, Fondation Lenval
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02565524
- Sponsor's protocol ID
- 14-HPNCL08
- Acronym
- GenAuDiss
- Status last verified
- Sep 2023
- First submitted
- 29 Jul 2015
- Last updated
- 29 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Fernandez A, Dor E, Maurin T, Laure G, Menard ML, Drozd M, Poinso F, Bardoni B, Askenazy F, Thummler S. Exploration and characterisation of the phenotypic and genetic profiles of patients with early onset schizophrenia associated with autism spectrum disorder and their first-degree relatives: a French multicentre case series study protocol (GenAuDiss). BMJ Open. 2018 Jul 5;8(7):e023330. doi: 10.1136/bmjopen-2018-023330.
PubMed 29980548
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploration and Characterization of the Phenotypic and Genetic Profile of Patients With Early Onset Schizophrenia Associated With Autism Spectrum Disorder and Their First-degree Relatives (GenAuDiss).
- ClinicalTrials.gov ID
- NCT02565524
- Acronym / sponsor ID
- GenAuDiss / 14-HPNCL08
- Conditions
- Schizophrenia, Dissociative Disorders
- Keywords
- schizophrenia, early dissociative disorder, genetic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 111 participants (actual)
- Lead sponsor
- Fondation LenvalUniversity, hospital or other
- Study start
- 18 May 2014 (actual)
- Primary completion
- 30 May 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 1 Oct 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.
Early onset schizophrenia "early dissociative disorder" is a rare disorder with a low incidence of approximately (1/5000 to 1/20000). Its link with autism spectrum disorders remains unknown although both are serious neurodevelopmental diseases. As part of the 2011-2013 Interregional hospital Clinical Research program, University Department of Child and Adolescent Psychiatry Pediatric Hospitals of CHU de Nice Lenval identified patients with a complex phenotype characterized by an early schizophrenia associated with autism spectrum disorders and developmental disabilities in mild to moderate. This phenotype could be a new syndrome.
The goal of our project is to define the genetic causes of this phenotype. The technique of high throughput sequencing will be used to obtain the sequence of exomes of these patients and their families. This study will therefore be important to give an accurate diagnosis for patients and their families. Moreover, we believe that this project will identify new genes involved allowing a better understanding of the pathophysiology. Recent studies show the involvement of mutations in several genes (eg NRXN1 and UPF3B) in these different clinical phenotypes. However, the genetic basis of the childhood and early onset schizophrenia are much less well known than those of autism spectrum disorder
Detailed description
Introduction: Early-onset Schizophrenia (EOS) is a rare and severe condition displaying early dissociative disorder (i.e., age of onset < 18 years). A higher rate of neurodevelopmental abnormalities is observed in EOS compared to adult onset schizophrenia (AOS). Thus, patients affected by EOS typically present intellectual, learning, communication or neuromotor impairments, as well as attention deficit hyperactivity disorder. Early signs of autism spectrum disorders (ASD) are also found in 30% of patients with EOS.
Cytogenetics abnormalities, including copy number variations (CNVs), are frequent in neurodevelopmental disorders and have been linked to ASD physiopathology. Implicated genes encode proteins playing a role in brain development, synaptic morphology, plasticity and neurogenesis. In addition, an increasing number of genetic abnormalities are shared by EOS and ASD, suggesting that schizophrenia can be considered a neurodevelopmental disorder.
The main objective of the present study is to identify mutations in genes involved in neurodevelopmental pathways in our cohort of patients affected by both EOS and ASD.
Method and analysis: We describe here a multicenter study in a pediatric population named "Exploration and characterization of genetic and phenotypic profile of the 'early dissociative disorder' associated with autism spectrum disorder (GenAuDiss)". The study started in April 2014. The inclusion criteria are: age 7 to 22 years, diagnoses of EOS with co-morbid ASD and IQ > 50; as well as parents and siblings of the included patients.
We perform standardized psychiatric assessments (MINI, K-SADS-PL, PANSS, SANS, TCI 226, and AQ) and neurocognitive evaluations (IQ, TMT A/B, and verbal fluency). Then, we study variants of the coding part of the DNA (exome), using next generation sequencing (NGS) process on trio (mother, father, and child). Divers bio-informatics tools such as RVIS and PolyPhen-2 will be used to prioritize the potential candidate genes. The inclusion period of this study will end in November 2019.
Ethics and dissemination: The study protocol was approved by the Ethics Committee 'Sud Méditerrané V' (number 14.002) and by the French National Agency for Medicines and Health Products Safety (ANSM 2013-A01699-36). All patients, their parents and siblings signed informed consent upon enrolment in the study.
Results of the present study should help to unravel the molecular pathology of EOS, paving the way for an early therapeutic intervention
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| genetic and phenotypic profile | Experimental | Other: genetic and phenotypic profileblood sample, clinical and neurocognitive assessment |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (19 listed)
- ≥ 7 years, <18 (below 7 years the diagnosis of schizophrenia is not possible)
- Schizophrenia Diagnosis done using the diagnostic tool Kiddie sads
- Autism Diagnosis done using the diagnostic scale Autism Diagnostic interview (ADI-R)
- Intelligence quotient (IQ) ≥ 50 at Wechsler Intelligence Scale for Children (WISC) IV abridged version
- Clinical examination
Key exclusion criteria (9 listed)
- Children refusing to participate
- Children without verbal language
- Children refusing to participate
- Adults protected by law
- Refusing to participate
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 |
|---|---|---|
| genetic and phenotypic profileGenetic and phenotypic profile, clinical and neurocognitive assessment for child with Schizophrenia and autism, their parents and brotherhood | Other | genetic and phenotypic profile |
Primary outcome
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing standard karyotype
Time frame: inclusion visit
A standard karyotype at a resolution of 300 to 400 bands per haploid lot. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions. A standard karyotype at a resolution of 300 to 400 bands per haploid lot is established initially. It can diagnose numerical anomalies and certain structural abnormalities such as reciprocal translocations, inversions, deletions Big. The pathological nature of these mutations will be stutied on the gene function and reaches its pattern of expression.
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing search CGG
Time frame: inclusion visit
A search of the CGG expansion hypermethylated in the 5 'UTR of the FMR1 gene mutation that causes Fragile X syndrome.
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing whole exome sequencing
Time frame: inclusion visit
Whole Exome Sequencing on trio (mother, father and child); This technology has demonstrated its power in recent years to determine the genetic causes of many rare diseases (Ropers, HH., 2012).
6 secondary outcomes
Intensity of positive symptoms of schizophrenia
Time frame: inclusion visit
Co-morbid psychiatric diagnosis
Time frame: inclusion visit
Evaluation of executive and attentional by the verbal fluency test
Time frame: inclusion visit
Clinical evaluation of autistic symptoms
Time frame: inclusion visit
Neurocognitive profile
Time frame: inclusion visit
Personality dimensional test
Time frame: inclusion visit
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 29 Sep 2023.
- Derived from this study: PubMed 29980548Fernandez A, Dor E, Maurin T, Laure G, Menard ML, Drozd M, Poinso F, Bardoni B, Askenazy F, Thummler S. Exploration and characterisation of the phenotypic and genetic profiles of patients with early onset schizophrenia associated with autism spectrum disorder and their first-degree relatives: a French multicentre case series study protocol (GenAuDiss). BMJ Open. 2018 Jul 5;8(7):e023330. doi: 10.1136/bmjopen-2018-023330.
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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.
Emmanuelle DOR, MD principal investigator
Fondation Lenval
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing genetic and phenotypic profile in people with Schizophrenia and Dissociative Disorders, run by Fondation Lenval 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 19 inclusion and 9 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 29 Sep 2023. 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?
characterization of the genetic abnormalities associated to Early Onset Schizophrenia phenotypes by performing standard karyotype (time frame: inclusion visit). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02565524, which also lists 1 linked publication.
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 29 Sep 2023.