Preimplantation Genetic DiagnosisNCT01336400
Genome-wide Single Cell Haplotyping as a Generic Method for Preimplantation Genetic Diagnosis
An observational study of Preimplantation Genetic Diagnosis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
The investigators previously developed approaches to SNP-, CNV- and haplo-type single human cells (Vanneste et al. 2009, Nature Medicine). These methods open the possibility to be developed into a novel generic diagnostic technique which broadens the spectrum of disease-alleles that can be selected against during… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Preimplantation Genetic Diagnosis
- What is being tested?
- single cell haplotyping
- How many people
- 60 participants
- Where
- 1 siteBelgium
- Study dates
- Oct 2010to Sep 2013
- 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: We aim to collect spare embryos of 30 couples that opt for preimplantation genetic diagnosis (see Eligibility Criteria).
Who may be able to join
- Blastomeres biopsied from spare embryos ((A) Embryos diagnosed as genetically abnormal using current PCR- and FISH-protocols; (B) Embryos diagnosed as normal for the investigated region using current PCR- and FISH-protocols, but not of sufficient quality to be transferred or frozen; (C) Embryos of the sex that is selected against following PGD based sex-selection, or embryos of the sex that is selected for but of insufficient quality to be transferred or frozen; (D) Embryos that were not biopsied in a PGD cycle since they suffer a slight growth delay.) derived from following patient groups:
- The first patient group involve couples suffering a complex chromosomal rearrangement (CCR), which is defined as a structural chromosomal rearrangement with at least three breakpoints and an exchange of genetic material between two or more chromosomes.
- The second patient group involve couples with X-linked recessive disorders.
- The third patient group consists of couples that carry a balanced chromosomal rearrangement - a translocation, insertion or inversion - that may result in recurrent miscarriage or aneuploid, severely handicapped offspring.
- A fourth patient group are couples at risk for the transmission of monogenic diseases.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Universitaire Ziekenhuizen Leuven
Leuven, Vlaams Brabant, 3000
Joris R Vermeesch, Professor, +32 16 345941, Joris.Vermeesch@uzleuven.be
Thierry Voet, Professor, +32 16 347991, Thierry.Voet@med.kuleuven.be
About this study
The investigators previously developed approaches to SNP-, CNV- and haplo-type single human cells (Vanneste et al. 2009, Nature Medicine). These methods open the possibility to be developed into a novel generic diagnostic technique which broadens the spectrum of disease-alleles that can be selected against during preimplantation genetic diagnosis (PGD) and which enables to help those couples that cannot be supported by PGD yet. PGD is the genetic analysis of a single blastomere from an in vitro fertilized (IVF) embryo and it is offered to couples to avoid the transmission of heritable genetic disorders to their offspring. PGD analyses are performed for (1) autosomal dominant or recessive monogenic diseases, (2) X-linked disorders and (3) chromosomal aberrations that may result in aneuploid conceptions. This novel method is likely to outperform and hence, replace current techniques for preimplantation genetic diagnosis. In this project the investigators will bring the technology from a proof-of-principle to the clinical application. To this end the investigators will make computational improvements for accurate single blastomere SNP-, CNV- and haplo-typing and perform a large validation study. For the validation studythe investigators will analyse the genomes of the blastomeres derived from 60 spare embryos of different origin: (1) Embryos diagnosed as genetically abnormal using current PCR- and FISH-protocols. (2) Embryos diagnosed as normal for the investigated region using current PCR- and FISH-protocols, but not of sufficient quality to be transferred or frozen. (3) Embryos of the sex that is selected against following PGD based sex-selection, or embryos of the sex that is selected for but of insufficient quality to be transferred or frozen. (4) Embryos that were not biopsied in a PGD cycle since they suffer a slight growth delay. This validation study will allow us to evaluate (1) the clinical validity (false positive and negative rate) and (2) clinical applicability (in terms of ease of use, success rate, etc.). In addition, it will bring us essential further fundamental insights in the origins and mechanisms of chromosomal instability operating during early embryogenesis and its consequences for clinical applications of PGD. Finally, following the validation study, this project will clinically implement the technique to treat 10 families.
- Conditions
- Preimplantation Genetic Diagnosis
- Being tested
- single cell haplotyping
- Keywords
- Single cell haplotyping, Preimplantation genetic diagnosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
single cell haplotypingOther
We aim to collect single blastomeres from spare IVF embryos of 30 couples to optimize and test methods for single cell haplotyping. We aim to collect 20 and 10 couples coming to the fertility centre for FISH- or PCR-based PGD respectively. In both groups, at least 5 different indications for PGD will be collected. Per couple, we will perform 10 SNP-arrays: 2 for the couple donating the embryo, 4 for family members (often parents of the couple) and 4 for blastomeres since we aim to pick 2 cells from 2 embryos per couple. For five couples, 2 blastomeres of all available embryos will be aspirated to validate and optimize the phasing methods. Finally, for some embryos, all blastomeres will be picked to be able to prove the reproducibility of single cell haplotyping.
| Study group | Role | What they receive |
|---|---|---|
| PGD-FISH | Following couples opting for preimplantation genetic diagnosis on the basis of FISH:
* couples suffering a complex chromosomal rearrangement (CCR)
* couples with X-linked recessive disorders
* couples that carry a balanced chromosomal rearrangement Receives: Other: single cell haplotyping | |
| PGD-PCR | Following couples opting for preimplantation genetic diagnosis on the basis of PCR:
-couples at risk for the transmission of monogenic diseases Receives: Other: single cell haplotyping |
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2011 (estimated)
- Study startOct 2010
- Primary completionSep 2013 (estimated)
- Study completionSep 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Preimplantation Genetic DiagnosisStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel
- Investigators
- Joris R Vermeesch, Professor, Principal investigator, Universitaire Ziekenhuizen KU LeuvenThierry Voet, Professor, Principal investigator, KU LeuvenThomas D'Hooghe, Professor, Principal investigator, Universitaire Ziekenhuizen KU LeuvenYves Moreau, Professor, Principal investigator, KU LeuvenKaren Sermon, Professor, Principal investigator, Vrije Universiteit BrusselDe Rycke Martine, Professor, Principal investigator, Universitair Ziekenhuis Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01336400
- Sponsor's protocol ID
- IWT-TBM-090878
- Status last verified
- Apr 2010
- First submitted
- 13 Apr 2011
- Last updated
- 15 Apr 2011
- Results posted
- No
- Data monitoring committee
- No
Publications
Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P, Melotte C, Debrock S, Amyere M, Vikkula M, Schuit F, Fryns JP, Verbeke G, D'Hooghe T, Moreau Y, Vermeesch JR. Chromosome instability is common in human cleavage-stage embryos. Nat Med. 2009 May;15(5):577-83. doi: 10.1038/nm.1924. Epub 2009 Apr 26.
PubMed 19396175Vanneste E, Voet T, Melotte C, Debrock S, Sermon K, Staessen C, Liebaers I, Fryns JP, D'Hooghe T, Vermeesch JR. What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate. Hum Reprod. 2009 Nov;24(11):2679-82. doi: 10.1093/humrep/dep266. Epub 2009 Jul 24.
PubMed 19633308
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genome-wide Single Cell Haplotyping as a Generic Method for Preimplantation Genetic Diagnosis
- ClinicalTrials.gov ID
- NCT01336400
- Acronym / sponsor ID
- IWT-TBM-090878
- Conditions
- Preimplantation Genetic Diagnosis
- Keywords
- Single cell haplotyping, Preimplantation genetic diagnosis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- KU Leuven, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel
- Study start
- Oct 2010
- Primary completion
- Sep 2013 (estimated)
- Study completion
- Sep 2013 (estimated)
- First posted
- 15 Apr 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.
The investigators previously developed approaches to SNP-, CNV- and haplo-type single human cells (Vanneste et al. 2009, Nature Medicine). These methods open the possibility to be developed into a novel generic diagnostic technique which broadens the spectrum of disease-alleles that can be selected against during preimplantation genetic diagnosis (PGD) and which enables to help those couples that cannot be supported by PGD yet. PGD is the genetic analysis of a single blastomere from an in vitro fertilized (IVF) embryo and it is offered to couples to avoid the transmission of heritable genetic disorders to their offspring. PGD analyses are performed for (1) autosomal dominant or recessive monogenic diseases, (2) X-linked disorders and (3) chromosomal aberrations that may result in aneuploid conceptions. This novel method is likely to outperform and hence, replace current techniques for preimplantation genetic diagnosis. In this project the investigators will bring the technology from a proof-of-principle to the clinical application. To this end the investigators will make computational improvements for accurate single blastomere SNP-, CNV- and haplo-typing and perform a large validation study. For the validation studythe investigators will analyse the genomes of the blastomeres derived from 60 spare embryos of different origin: (1) Embryos diagnosed as genetically abnormal using current PCR- and FISH-protocols. (2) Embryos diagnosed as normal for the investigated region using current PCR- and FISH-protocols, but not of sufficient quality to be transferred or frozen. (3) Embryos of the sex that is selected against following PGD based sex-selection, or embryos of the sex that is selected for but of insufficient quality to be transferred or frozen. (4) Embryos that were not biopsied in a PGD cycle since they suffer a slight growth delay. This validation study will allow us to evaluate (1) the clinical validity (false positive and negative rate) and (2) clinical applicability (in terms of ease of use, success rate, etc.). In addition, it will bring us essential further fundamental insights in the origins and mechanisms of chromosomal instability operating during early embryogenesis and its consequences for clinical applications of PGD. Finally, following the validation study, this project will clinically implement the technique to treat 10 families.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PGD-FISH | – | Other: single cell haplotypingFollowing couples opting for preimplantation genetic diagnosis on the basis of FISH: * couples suffering a complex chromosomal rearrangement (CCR) * couples with X-linked recessive disorders * couples that carry a balanced chromosomal rearrangement |
| PGD-PCR | – | Other: single cell haplotypingFollowing couples opting for preimplantation genetic diagnosis on the basis of PCR: -couples at risk for the transmission of monogenic diseases |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- We aim to collect spare embryos of 30 couples that opt for preimplantation genetic diagnosis (see Eligibility Criteria).
Key inclusion criteria (5 listed)
- Blastomeres biopsied from spare embryos ((A) Embryos diagnosed as genetically abnormal using current PCR- and FISH-protocols; (B) Embryos diagnosed as normal for the investigated region using current PCR- and FISH-protocols, but not of sufficient quality to be transferred or frozen; (C) Embryos of the sex that is selected against following PGD based sex-selection, or embryos of the sex that is selected for but of insufficient quality to be transferred or frozen; (D) Embryos that were not biopsied in a PGD cycle since they suffer a slight growth delay.) derived from following patient groups:
- The first patient group involve couples suffering a complex chromosomal rearrangement (CCR), which is defined as a structural chromosomal rearrangement with at least three breakpoints and an exchange of genetic material between two or more chromosomes.
- The second patient group involve couples with X-linked recessive disorders.
- The third patient group consists of couples that carry a balanced chromosomal rearrangement - a translocation, insertion or inversion - that may result in recurrent miscarriage or aneuploid, severely handicapped offspring.
- A fourth patient group are couples at risk for the transmission of monogenic diseases.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| single cell haplotypingWe aim to collect single blastomeres from spare IVF embryos of 30 couples to optimize and test methods for single cell haplotyping. We aim to collect 20 and 10 couples coming to the fertility centre for FISH- or PCR-based PGD respectively. In both groups, at least 5 different indications for PGD will be collected. Per couple, we will perform 10 SNP-arrays: 2 for the couple donating the embryo, 4 for family members (often parents of the couple) and 4 for blastomeres since we aim to pick 2 cells from 2 embryos per couple. For five couples, 2 blastomeres of all available embryos will be aspirated to validate and optimize the phasing methods. Finally, for some embryos, all blastomeres will be picked to be able to prove the reproducibility of single cell haplotyping. | Other | PGD-FISH, PGD-PCR |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2011.
- Background: PubMed 19396175Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P, Melotte C, Debrock S, Amyere M, Vikkula M, Schuit F, Fryns JP, Verbeke G, D'Hooghe T, Moreau Y, Vermeesch JR. Chromosome instability is common in human cleavage-stage embryos. Nat Med. 2009 May;15(5):577-83. doi: 10.1038/nm.1924. Epub 2009 Apr 26.
- Background: PubMed 19633308Vanneste E, Voet T, Melotte C, Debrock S, Sermon K, Staessen C, Liebaers I, Fryns JP, D'Hooghe T, Vermeesch JR. What next for preimplantation genetic screening? High mitotic chromosome instability rate provides the biological basis for the low success rate. Hum Reprod. 2009 Nov;24(11):2679-82. doi: 10.1093/humrep/dep266. Epub 2009 Jul 24.
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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.
Joris R Vermeesch, Professor principal investigator
Universitaire Ziekenhuizen KU Leuven
Thierry Voet, Professor principal investigator
KU Leuven
Thomas D'Hooghe, Professor principal investigator
Universitaire Ziekenhuizen KU Leuven
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 Preimplantation Genetic Diagnosis, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 0 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 15 Apr 2011. 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 Belgium. 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 Joris R Vermeesch, Professor (+32 16 345941, Joris.Vermeesch@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01336400, which also lists 2 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 15 Apr 2011.