Intellectual DeficiencyRementipsNCT02980302
Development of the Tool " iPSC " for the Functional Study of Mutations Responsible for Mental Retardation
A study testing Cutaneous biopsy in people with Intellectual Deficiency and Asymptomatic Carrier of the Mutation of the Gene MYT1L, run by University Hospital, Grenoble at 1 site in France.
Trial summary
According to the World Health Organization (WHO), mental retardation (MR) is defined by an intelligence quotient (IQ) < 70 and touches between 1 to 3 % of the general population. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Intellectual Deficiency, Asymptomatic Carrier of the Mutation of the Gene MYT1L, Healthy Volunteers
- What is being tested?
- Cutaneous biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2015to Sep 2017
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Patient with an intellectual deficiency and/or associated signs that received a chromosomic analysis by CGH-array revealing a variant of unknown signification involvingone or more genes candidates for mental retardation.
- Certificate of genetic genetic counselling and signed consent.
- Under 18 persons may be necessary because intellectual deficiency is often diagnosed before the adult age.
- Number of cases is very limited in this preliminary study and only one patient showing a rare mutation of MYT1L gene and his father ( asymptomatic carrier of the same mutation) will be study.
- Affiliation to a social security system
Who cannot join
- Persons mentionned L1121-5 to L1121-8 of CSP (all protected persons)
- Persons suffering from acute infections for the practice of cutaneous biopsy under local anesthesia.
- Persons showing an hemostasis disorder acquired or induced
- Persons sous traitement antiagrégant anticoagulant
- Persons with a mutation in th gene MYT1L
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Development of the Tool " iPSC " (Induced Pluripotent Stem Cells) for the Functional Study of Mutations Responsible for Mental Retardation - Application to Familial Study of MYT1L Gene Mutations
According to the World Health Organization (WHO), mental retardation (MR) is defined by an intelligence quotient (IQ) < 70 and touches between 1 to 3 % of the general population. Profound mental retardation (QI <25), severe (IQ: 25-40) and moderate (QI : 40-50) have a prevalence of 0,3-0,5% while the prevalence of mild MR, defined by an IQ between 50 and 70 is evaluated to about 1,5 %.
The origin of MR can be infectious, toxic, traumatic, genetic or environmental. genetic causes of MR gather the number and structure anomalies of the chromosomes, the genomic microreorganization, monogenic diseases and more rarely other non Mendelian-inherited anomalies like print or epigenetic anomalies, mutations of the mitochondrial genome etc... Genetic causes represents 50% of moderate to severe, whereas environmental factors (malnutrition, cultural deprivation,...) plays an important role in mild MR.
Read more
The main goal of this study is to get an innovative tool (neuronal distinction of iPSC) that wil allow to study the functionnal impact of mutations uppon genes probably involved in MR like MYT1L. The main criteria associated to characterisation of the tool by the trial is the study of the pluripotency of iPSC obtained and to highlight the mutation of the gene MYT1L in the iPSC.
Neurons from the iPSC of the patient and his father du patient wille also be morphologically characterised, but also thanks to the expression of specifically neurals genes.
Characteristics of iPSC and neurons from d'iPSC with MYT1L mutation will be compared among the patient and his father, in relation with the same cells coming from the two witnesses.
- Conditions
- Intellectual Deficiency, Asymptomatic Carrier of the Mutation of the Gene MYT1L, Healthy Volunteers
- Being tested
- Cutaneous biopsy
- Keywords
- Mental retardation MR, IQ, Mutation, Gene MYT1L
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cutaneous biopsyProcedure or surgery
Under local anesthesia
| Study group | Role | What they receive |
|---|---|---|
| Patient | Other | Not described Receives: Procedure: Cutaneous biopsy |
| Asymptomatic carrier | Other | Father of the patient : asymptomatic carrier of the same mutation Receives: Procedure: Cutaneous biopsy |
| Two control patients | Other | Not described Receives: Procedure: Cutaneous biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
iPSC caracterization from human fibroblast with MYT1L mutation
Skin sampling under local anesthesia. Evaluation of iPSC gene expression for their pluripotency.
Measured: Half an hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study startSep 2015
- Primary completionJun 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Intellectual DeficiencyStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre Simon Jouk, Professor, Principal investigator, Grenoble Hospital University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02980302
- Sponsor's protocol ID
- 38RC14.181
- Acronym
- Rementips
- Status last verified
- Oct 2018
- First submitted
- 28 Jul 2016
- Last updated
- 12 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Bonnet C, Leheup B, Beri M, Philippe C, Gregoire MJ, Jonveaux P. Aberrant GRIA3 transcripts with multi-exon duplications in a family with X-linked mental retardation. Am J Med Genet A. 2009 Jun;149A(6):1280-9. doi: 10.1002/ajmg.a.32858.
PubMed 19449417Brosco JP, Mattingly M, Sanders LM. Impact of specific medical interventions on reducing the prevalence of mental retardation. Arch Pediatr Adolesc Med. 2006 Mar;160(3):302-9. doi: 10.1001/archpedi.160.3.302.
PubMed 16520451Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009 Mar;27(3):275-80. doi: 10.1038/nbt.1529. Epub 2009 Mar 1.
PubMed 19252484Chanda S, Marro S, Wernig M, Sudhof TC. Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16622-7. doi: 10.1073/pnas.1316240110. Epub 2013 Sep 17.
PubMed 24046374Chiurazzi P, Schwartz CE, Gecz J, Neri G. XLMR genes: update 2007. Eur J Hum Genet. 2008 Apr;16(4):422-34. doi: 10.1038/sj.ejhg.5201994. Epub 2008 Jan 16.
PubMed 18197188Chiyonobu T, Hayashi S, Kobayashi K, Morimoto M, Miyanomae Y, Nishimura A, Nishimoto A, Ito C, Imoto I, Sugimoto T, Jia Z, Inazawa J, Toda T. Partial tandem duplication of GRIA3 in a male with mental retardation. Am J Med Genet A. 2007 Jul 1;143A(13):1448-55. doi: 10.1002/ajmg.a.31798.
PubMed 17568425Cohn DM, Pagon RA, Hudgins L, Schwartz CE, Stevenson RE, Friez MJ. Partial ATRX gene duplication causes ATR-X syndrome. Am J Med Genet A. 2009 Oct;149A(10):2317-20. doi: 10.1002/ajmg.a.33006. No abstract available.
PubMed 19764021Doco-Fenzy M, Leroy C, Schneider A, Petit F, Delrue MA, Andrieux J, Perrin-Sabourin L, Landais E, Aboura A, Puechberty J, Girard M, Tournaire M, Sanchez E, Rooryck C, Ameil A, Goossens M, Jonveaux P, Lefort G, Taine L, Cailley D, Gaillard D, Leheup B, Sarda P, Genevieve D. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes. Eur J Hum Genet. 2014 Apr;22(4):471-9. doi: 10.1038/ejhg.2013.189. Epub 2013 Oct 16.
PubMed 24129437Froyen G, Belet S, Martinez F, Santos-Reboucas CB, Declercq M, Verbeeck J, Donckers L, Berland S, Mayo S, Rosello M, Pimentel MM, Fintelman-Rodrigues N, Hovland R, Rodrigues dos Santos S, Raymond FL, Bose T, Corbett MA, Sheffield L, van Ravenswaaij-Arts CM, Dijkhuizen T, Coutton C, Satre V, Siu V, Marynen P. Copy-number gains of HUWE1 due to replication- and recombination-based rearrangements. Am J Hum Genet. 2012 Aug 10;91(2):252-64. doi: 10.1016/j.ajhg.2012.06.010. Epub 2012 Jul 26.
PubMed 22840365Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST; Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011 Jul;13(7):680-5. doi: 10.1097/GIM.0b013e3182217a3a.
PubMed 21681106Kleinjan DA, van Heyningen V. Long-range control of gene expression: emerging mechanisms and disruption in disease. Am J Hum Genet. 2005 Jan;76(1):8-32. doi: 10.1086/426833. Epub 2004 Nov 17.
PubMed 15549674Larson SA, Lakin KC, Anderson L, Kwak N, Lee JH, Anderson D. Prevalence of mental retardation and developmental disabilities: estimates from the 1994/1995 National Health Interview Survey Disability Supplements. Am J Ment Retard. 2001 May;106(3):231-52.
PubMed 11408960Lee C, Iafrate AJ, Brothman AR. Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet. 2007 Jul;39(7 Suppl):S48-54. doi: 10.1038/ng2092.
PubMed 17597782Lujan E, Chanda S, Ahlenius H, Sudhof TC, Wernig M. Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells. Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2527-32. doi: 10.1073/pnas.1121003109. Epub 2012 Jan 30.
PubMed 22308465McLaren J, Bryson SE. Review of recent epidemiological studies of mental retardation: prevalence, associated disorders, and etiology. Am J Ment Retard. 1987 Nov;92(3):243-54.
PubMed 3322329
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of the Tool " iPSC " (Induced Pluripotent Stem Cells) for the Functional Study of Mutations Responsible for Mental Retardation - Application to Familial Study of MYT1L Gene Mutations
- ClinicalTrials.gov ID
- NCT02980302
- Acronym / sponsor ID
- Rementips / 38RC14.181
- Conditions
- Intellectual Deficiency, Asymptomatic Carrier of the Mutation of the Gene MYT1L, Healthy Volunteers
- Keywords
- Mental retardation MR, IQ, Mutation, Gene MYT1L
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- Jun 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 2 Dec 2016 (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.
According to the World Health Organization (WHO), mental retardation (MR) is defined by an intelligence quotient (IQ) < 70 and touches between 1 to 3 % of the general population. Profound mental retardation (QI <25), severe (IQ: 25-40) and moderate (QI : 40-50) have a prevalence of 0,3-0,5% while the prevalence of mild MR, defined by an IQ between 50 and 70 is evaluated to about 1,5 %.
The origin of MR can be infectious, toxic, traumatic, genetic or environmental. genetic causes of MR gather the number and structure anomalies of the chromosomes, the genomic microreorganization, monogenic diseases and more rarely other non Mendelian-inherited anomalies like print or epigenetic anomalies, mutations of the mitochondrial genome etc... Genetic causes represents 50% of moderate to severe, whereas environmental factors (malnutrition, cultural deprivation,...) plays an important role in mild MR.
The main goal of this study is to get an innovative tool (neuronal distinction of iPSC) that wil allow to study the functionnal impact of mutations uppon genes probably involved in MR like MYT1L. The main criteria associated to characterisation of the tool by the trial is the study of the pluripotency of iPSC obtained and to highlight the mutation of the gene MYT1L in the iPSC.
Neurons from the iPSC of the patient and his father du patient wille also be morphologically characterised, but also thanks to the expression of specifically neurals genes.
Characteristics of iPSC and neurons from d'iPSC with MYT1L mutation will be compared among the patient and his father, in relation with the same cells coming from the two witnesses.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patient | Other | Procedure: Cutaneous biopsy |
| Asymptomatic carrier | Other | Procedure: Cutaneous biopsyFather of the patient : asymptomatic carrier of the same mutation |
| Two control patients | Other | Procedure: Cutaneous biopsy |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patient with an intellectual deficiency and/or associated signs that received a chromosomic analysis by CGH-array revealing a variant of unknown signification involvingone or more genes candidates for mental retardation.
- Certificate of genetic genetic counselling and signed consent.
- Under 18 persons may be necessary because intellectual deficiency is often diagnosed before the adult age.
- Number of cases is very limited in this preliminary study and only one patient showing a rare mutation of MYT1L gene and his father ( asymptomatic carrier of the same mutation) will be study.
- Affiliation to a social security system
Key exclusion criteria (5 listed)
- Persons mentionned L1121-5 to L1121-8 of CSP (all protected persons)
- Persons suffering from acute infections for the practice of cutaneous biopsy under local anesthesia.
- Persons showing an hemostasis disorder acquired or induced
- Persons sous traitement antiagrégant anticoagulant
- Persons with a mutation in th gene MYT1L
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 |
|---|---|---|
| Cutaneous biopsyUnder local anesthesia | Procedure or surgery | Asymptomatic carrier, Patient, Two control patients |
Primary outcome
iPSC caracterization from human fibroblast with MYT1L mutation
Time frame: Half an hour
Skin sampling under local anesthesia. Evaluation of iPSC gene expression for their pluripotency.
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 12 Oct 2018.
- Background: PubMed 19449417Bonnet C, Leheup B, Beri M, Philippe C, Gregoire MJ, Jonveaux P. Aberrant GRIA3 transcripts with multi-exon duplications in a family with X-linked mental retardation. Am J Med Genet A. 2009 Jun;149A(6):1280-9. doi: 10.1002/ajmg.a.32858.
- Background: PubMed 16520451Brosco JP, Mattingly M, Sanders LM. Impact of specific medical interventions on reducing the prevalence of mental retardation. Arch Pediatr Adolesc Med. 2006 Mar;160(3):302-9. doi: 10.1001/archpedi.160.3.302.
- Background: PubMed 19252484Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol. 2009 Mar;27(3):275-80. doi: 10.1038/nbt.1529. Epub 2009 Mar 1.
- Background: PubMed 24046374Chanda S, Marro S, Wernig M, Sudhof TC. Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation. Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16622-7. doi: 10.1073/pnas.1316240110. Epub 2013 Sep 17.
- Background: PubMed 18197188Chiurazzi P, Schwartz CE, Gecz J, Neri G. XLMR genes: update 2007. Eur J Hum Genet. 2008 Apr;16(4):422-34. doi: 10.1038/sj.ejhg.5201994. Epub 2008 Jan 16.
- Background: PubMed 17568425Chiyonobu T, Hayashi S, Kobayashi K, Morimoto M, Miyanomae Y, Nishimura A, Nishimoto A, Ito C, Imoto I, Sugimoto T, Jia Z, Inazawa J, Toda T. Partial tandem duplication of GRIA3 in a male with mental retardation. Am J Med Genet A. 2007 Jul 1;143A(13):1448-55. doi: 10.1002/ajmg.a.31798.
- Background: PubMed 19764021Cohn DM, Pagon RA, Hudgins L, Schwartz CE, Stevenson RE, Friez MJ. Partial ATRX gene duplication causes ATR-X syndrome. Am J Med Genet A. 2009 Oct;149A(10):2317-20. doi: 10.1002/ajmg.a.33006. No abstract available.
- Background: PubMed 24129437Doco-Fenzy M, Leroy C, Schneider A, Petit F, Delrue MA, Andrieux J, Perrin-Sabourin L, Landais E, Aboura A, Puechberty J, Girard M, Tournaire M, Sanchez E, Rooryck C, Ameil A, Goossens M, Jonveaux P, Lefort G, Taine L, Cailley D, Gaillard D, Leheup B, Sarda P, Genevieve D. Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes. Eur J Hum Genet. 2014 Apr;22(4):471-9. doi: 10.1038/ejhg.2013.189. Epub 2013 Oct 16.
- Background: PubMed 22840365Froyen G, Belet S, Martinez F, Santos-Reboucas CB, Declercq M, Verbeeck J, Donckers L, Berland S, Mayo S, Rosello M, Pimentel MM, Fintelman-Rodrigues N, Hovland R, Rodrigues dos Santos S, Raymond FL, Bose T, Corbett MA, Sheffield L, van Ravenswaaij-Arts CM, Dijkhuizen T, Coutton C, Satre V, Siu V, Marynen P. Copy-number gains of HUWE1 due to replication- and recombination-based rearrangements. Am J Hum Genet. 2012 Aug 10;91(2):252-64. doi: 10.1016/j.ajhg.2012.06.010. Epub 2012 Jul 26.
- Background: PubMed 21681106Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST; Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med. 2011 Jul;13(7):680-5. doi: 10.1097/GIM.0b013e3182217a3a.
- Background: PubMed 15549674Kleinjan DA, van Heyningen V. Long-range control of gene expression: emerging mechanisms and disruption in disease. Am J Hum Genet. 2005 Jan;76(1):8-32. doi: 10.1086/426833. Epub 2004 Nov 17.
- Background: PubMed 11408960Larson SA, Lakin KC, Anderson L, Kwak N, Lee JH, Anderson D. Prevalence of mental retardation and developmental disabilities: estimates from the 1994/1995 National Health Interview Survey Disability Supplements. Am J Ment Retard. 2001 May;106(3):231-52.
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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.
Pierre Simon Jouk, Professor principal investigator
Grenoble Hospital University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cutaneous biopsy in people with Intellectual Deficiency and Asymptomatic Carrier of the Mutation of the Gene MYT1L, run by University Hospital, Grenoble 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 5 inclusion and 5 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 12 Oct 2018. 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?
iPSC caracterization from human fibroblast with MYT1L mutation (time frame: Half an hour). 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 NCT02980302, which also lists 28 linked publications.
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 12 Oct 2018.