Di George SyndromeCSRK05NCT04141540
Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11
A study testing Molecular analyses in people with Di George Syndrome, run by Hôpital le Vinatier at 1 site in France.
Trial summary
The 22q11.2 microdeletion syndrome (22q11.2DS) is a rare disease with a psychiatric phenotype. Indeed, the diagnosis of schizophrenia is made in 5 to 10% of adolescents and 25 to 40% of adults carrying the 22q11DS. Read more about this study
- Who is it for?
- Ages 18 to 45 years, men only
- Conditions the study is for
- Di George Syndrome
- What is being tested?
- Molecular analyses
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteFrance
- Study dates
- 27 Mar 2020to 30 Dec 2020
- 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 18 to 45 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- • Sisterhood of monozygotic twins diagnosed with de novo 22q11.2DS is confirmed by CGH array and discordant for the psychiatric phenotype
Who cannot join
- • Refusal to use data for research purposes
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Translational 22q11.2:"Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11.2 Microdeletional Syndrom"
The 22q11.2 microdeletion syndrome (22q11.2DS) is a rare disease with a psychiatric phenotype. Indeed, the diagnosis of schizophrenia is made in 5 to 10% of adolescents and 25 to 40% of adults carrying the 22q11DS. Thus, although this pathology has been able to provide a genetically homogeneous model for the study psychosis etiology, it is not currently possible to establish a link between genomic rearrangement and psychotic symptoms. However, this robust model of genetic vulnerability could provide us a lot of translational informations about schizophrenia genetics. To go furthermore, twin studies have provided us precious data for the study of hereditary diseases. Combining this two approaches, the translational 22q11.2 project proposes a molecular study of two monozygotic 22q11.2DS twins discordant for the psychiatric phenotype -one carrying schizophrenia and the other having no psychiatric symptoms-.
Read the detailed description
The main objective of the study is to propose a whole exome sequencing (WES), pan-genomic in whole genome sequencing (WGS), transcriptomic, epigenomic and intestinal microbiome approaches in order to determine specific molecular basis of psychotic symptoms in 22q11.2DS.
- Conditions
- Di George Syndrome
- Being tested
- Molecular analyses
- Keywords
- 22q11.2 Microdeletional
- Medical subject headings
- DiGeorge Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Molecular analysesGenetic
Comparaison of the molecular profil between two monozygotic twins carrying a deletion 22q11.2
| Study group | Role | What they receive |
|---|---|---|
| Groupe "Twin 1" | Other | Twin 1 with psychotic symptoms (PANSS +) Molecular analyses 1 Receives: Genetic: Molecular analyses |
| Groupe "Twin 2" | Other | Twin 2 without psychotic symptoms (PANSS +) Molecular analyses 2 Receives: Genetic: Molecular analyses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole exome sequencing
Searching for mosaic genetic variations that may have occurred secondarily to conception
Measured: 6 months
Secondary outcomes (6)
Transcriptome
two methods of mRNA extraction will be used: from the establishment of lymphoblastoid lines and from whole blood collected on paxgene® tube. After depletion of ribosomal RNA, the RNAs will be converted into complementary DNAs and libraries will be made using 100 to 200ng of total RNA. Libraries will be sequenced in a paired-end to generate 80 million reads per sample. The data will be analyzed with the HTSeq suite to count the number of reads associated with each gene annotated in the latest version of the genome. The DESeq bioconductor suite will be used to normalize the expression. A study to identify differentially expressed genes will be performed with this tool and GFold. Genes showing statistically significant differential expression will be validated by RT-qPCR
Measured: 6 months
Methylome
This analysis will be carried out in collaboration with " L'hôpital de Sainte Anne2 (Inserm UMR_S894 "Physiology of psychiatric diseases" - Professor Marie-Odile KREBS). The DNA will be extracted from whole blood collected on paxgene® tube. The methylation of the entire genome of twin siblings will be studied by the Infinium MethylationEPIC BeadChip chip (Illumina) that covers 850,000 CpG and the set of genes after bisulfite DNA processing. The statistical analysis of the methylation differences will be carried out with the R software (minfi and ChAMP packages) in order to highlight the DMP (Differentially Methylated Probes) as well as the DMR (Differentially Methylated Regions, probes contigues).
Measured: 6 months
Microbiotic DNA
A quantitative metagenomic analysis will be carried out on the basis of a sequencing of the genetic material extracted from the intestinal microbiome in the stools of the two twins
Measured: 6 months
Positive And Negative Syndrome Scale (PANSS)
Scale of evaluation of positive and negative syndromes of schizophrenic symptomatology.The patient is rated from 1 to 7 on 30 different symptoms based on the interview as well as reports of family members or primary care hospital workers.As 1 rather than 0 is given as the lowest score for each item, a patient can not score lower than 30 for the total PANSS score. Scores are often given separately for the positive items, negative items, and general psychopathology.
Measured: 6 months
Mini-International Neuropsychiatric Interview (MINI)
The modalities for answering all the Mini-International Neuropsychiatric Interview (MINI)questions are "YES" or "NO". If the answers to these filter questions are positive, the following ones are asked allowing to validate or invalidate the diagnosis concerned.
Measured: 6 months
Hospital Anxiety and Depression Scale (HADS)
The Hospital Anxiety and Depression Scale (HADS) is an instrument for detecting anxiety and depressive disorders. It has 14 listed items from 0 to 3. Seven questions relate to anxiety (total A) and seven others to the depressive dimension (total D), allowing thus obtaining two scores (maximum score of each score = 21).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2019
- Study start27 Mar 2020
- Primary completion30 Nov 2020
- Study completion30 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Di George SyndromeStudies of the same condition, open and under way.
- More trials run by Hôpital le VinatierThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- It's a study with a comparative monocentric cross-sectional analysis model.
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hôpital le Vinatier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- DEMILY CAROLINE, MD PH.D, Principal investigator, Centre Hospitalier le Vinatier & CNRS UMR 5229 (BRON, France)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04141540
- Sponsor's protocol ID
- 2019-A00852-55
- Acronym
- CSRK05
- Status last verified
- Jun 2020
- First submitted
- 24 Oct 2019
- Last updated
- 9 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Translational 22q11.2:"Molecular Variants Associated With Schizophrenia: Differential Analysis of Monozygotic Twins With Variable Phenotypic 22q11.2 Microdeletional Syndrom"
- ClinicalTrials.gov ID
- NCT04141540
- Acronym / sponsor ID
- CSRK05 / 2019-A00852-55
- Conditions
- Di George Syndrome
- Keywords
- 22q11.2 Microdeletional
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Hôpital le VinatierUniversity, hospital or other
- Study start
- 27 Mar 2020 (actual)
- Primary completion
- 30 Nov 2020 (actual)
- Study completion
- 30 Dec 2020 (actual)
- First posted
- 28 Oct 2019 (actual)
- 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.
The 22q11.2 microdeletion syndrome (22q11.2DS) is a rare disease with a psychiatric phenotype. Indeed, the diagnosis of schizophrenia is made in 5 to 10% of adolescents and 25 to 40% of adults carrying the 22q11DS. Thus, although this pathology has been able to provide a genetically homogeneous model for the study psychosis etiology, it is not currently possible to establish a link between genomic rearrangement and psychotic symptoms. However, this robust model of genetic vulnerability could provide us a lot of translational informations about schizophrenia genetics. To go furthermore, twin studies have provided us precious data for the study of hereditary diseases. Combining this two approaches, the translational 22q11.2 project proposes a molecular study of two monozygotic 22q11.2DS twins discordant for the psychiatric phenotype -one carrying schizophrenia and the other having no psychiatric symptoms-.
Detailed description
The main objective of the study is to propose a whole exome sequencing (WES), pan-genomic in whole genome sequencing (WGS), transcriptomic, epigenomic and intestinal microbiome approaches in order to determine specific molecular basis of psychotic symptoms in 22q11.2DS.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- It's a study with a comparative monocentric cross-sectional analysis model.
| Arm | Type | Receives |
|---|---|---|
| Groupe "Twin 1" | Other | Genetic: Molecular analysesTwin 1 with psychotic symptoms (PANSS +) Molecular analyses 1 |
| Groupe "Twin 2" | Other | Genetic: Molecular analysesTwin 2 without psychotic symptoms (PANSS +) Molecular analyses 2 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- • Sisterhood of monozygotic twins diagnosed with de novo 22q11.2DS is confirmed by CGH array and discordant for the psychiatric phenotype
Key exclusion criteria (1 listed)
- • Refusal to use data for research purposes
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 |
|---|---|---|
| Molecular analysesComparaison of the molecular profil between two monozygotic twins carrying a deletion 22q11.2 | Genetic | Groupe "Twin 1", Groupe "Twin 2" |
Primary outcome
Whole exome sequencing
Time frame: 6 months
Searching for mosaic genetic variations that may have occurred secondarily to conception
6 secondary outcomes
Transcriptome
Time frame: 6 months
Methylome
Time frame: 6 months
Microbiotic DNA
Time frame: 6 months
Positive And Negative Syndrome Scale (PANSS)
Time frame: 6 months
Mini-International Neuropsychiatric Interview (MINI)
Time frame: 6 months
Hospital Anxiety and Depression Scale (HADS)
Time frame: 6 months
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 9 Feb 2021.
- Individual participant dataSharing planned: No
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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.
DEMILY CAROLINE, MD PH.D principal investigator
Centre Hospitalier le Vinatier & CNRS UMR 5229 (BRON, France)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Molecular analyses in people with Di George Syndrome, run by Hôpital le Vinatier 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 1 inclusion and 1 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 9 Feb 2021. 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?
Whole exome sequencing (time frame: 6 months). 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 9 Feb 2021.