Genetic DiseasesMicroarrayNCT01279733
Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis
An observational study of Genetic Diseases, run by Columbia University at 1 site in United States.
Trial summary
The main objective of the multi-centered collaborative study is to evaluate the accuracy, efficacy and clinical advantages of prenatal diagnosis using microarray analysis as compared with conventional karyotyping. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Genetic Diseases
- What is being tested?
- Microarray analysis
- How many people
- 4,450 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to Oct 2011
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: A total of 4,400 prenatal diagnostic samples will be obtained from patients undergoing prenatal testing for standard indications. Patients will be recruited at participating prenatal diagnostic centers by designated study personnel; recruitment of patients will be initiated as a pilot study. These patients will not contribute to the final planned sample size of 4400 patients. Two sub-studies will then be initiated consisting of 250 (or more) patients enrolled with sufficient amniotic fluid sample and 250 (or more) patients with sufficient villus sample.
Who may be able to join
- Singleton pregnancy having either chorionic villus sampling in the first trimester or an amniocentesis procedure at or after 16 weeks of gestation performed for prenatal cytogenetic diagnosis
- Karyotyping to be performed at Genzyme Genetics Cytogenetics Laboratory
- Trained study personnel available
- Presenting at pre-specified sites using Genzyme Genetics for routine prenatal diagnostic services
Who cannot join
- Unavailability of one or both biologic parents to provide blood sample (e.g. egg or sperm donor, non-paternity)
- Patient refusal to allow follow-up through the neonatal period and up to age two if selected
- Participation in the study in a previous pregnancy
- Insufficient sample for microarray assay
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
The main objective of the multi-centered collaborative study is to evaluate the accuracy, efficacy and clinical advantages of prenatal diagnosis using microarray analysis as compared with conventional karyotyping.
Read the detailed description
Specifically, the aims are as follows:
- Demonstrate the performance of microarray analysis as a clinical method for prenatal cytogenetic diagnosis with regard to:
- Accuracy in the detection of the common autosomal and sex chromosomal aneuploid (trisomies, 13,18,21, 45,X, 47,XXY, etc.)
- Ability of microarray to diagnose less common, but clinically significant, cytogenetic aneusomies (e.g. DiGeorge, Williams, Smith- Magenis, Prader-Willi syndrome, etc.) currently not detected by conventional karyotype.
- Evaluation of the utility of microarray in specific clinical scenarios such as ultrasound detection of congenital anomalies and fetal growth disorders.
- Evaluate the appropriate construction of prenatal diagnostic microarray devices to allow maximal detection of clinically relevant information with minimal detection of unexpected and difficult to interpret findings which have no clinical significance but might provoke patient anxiety.
- Evaluate the feasibility and cost-effectiveness of using microarrays as a primary prenatal diagnostic tool.
- Evaluate approaches to integrate microarray into clinical prenatal cytogenetic diagnostic practice.
- Develop a prenatal diagnostic tissue repository (TDR) to facilitate the further development of microarray technology. This will be used to investigate the molecular etiologies of specific fetal anomalies and to test newer technologies, such as higher resolution microarrays.
- Conditions
- Genetic Diseases
- Being tested
- Microarray analysis
- Keywords
- microarray
- Medical subject headings
- Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Microarray analysisGenetic
Microarray performed on prenatal specimen:
Fluorescence in-situ hybridization (FISH) or other standardized tests such as qPCR or MLPA will be performed on the fetal sample to confirm abnormal MA findings of known and unknown clinical significance which are discordant with CC findings, including anomalies normally detected by karyotyping.
Microarray analysis of DNA from parental blood samples will be used to determine whether CNVs detected in a fetal sample are also present in a healthy parent, in which case no further evaluation will take place, moreover any finding in a fetus which is duplicated in a parental microarray is considered to be confirmed.
| Study group | Role | What they receive |
|---|---|---|
| Microarray Analysis | Not described Receives: Genetic: Microarray analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detection rate of fetal cytogentic abnormalites between microarray copy number analysis and karyotype in prenatal samples
This is a blinded prospective comparison of microarray copy number analysis to metaphase karyotyping for the detection of common fetal cytogentic abnormalites
Measured: Up to 2.5 years after recruitment of 4400 patients.
Secondary outcomes (2)
The ability of microarray copy number analysis to identify clinically significant microdeletions and duplications not seen by standard karyotyping
This outcome will identify the frequency of clinically significant microdeletions and microduplications that are identified on microarray CNA that were not seen on the clinical karyotype. Only copy number variants over 1 Mb in the backbone and those in predesignated critical regions will be included
Measured: Up to 2.5 years .
The rates of clinically significant copy number variants associated with specific prenatal conditions
THe frequency of clinically significant copy number variants in cases with fetal anomalies, advanced maternal age, positve serum screening, and fetal growth disorders will be determined.
Measured: Up to 2.5 years after recruitment of 4400 patients.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2011 (estimated)
- Study startOct 2008
- Primary completionOct 2011
- Study completionOct 2011
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 Genetic DiseasesStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 4,450 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Ronald J Wapner, MD, Columbia University
- Investigators
- Ronald Wapner, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01279733
- Sponsor's protocol ID
- AAAC8036
- Other IDs
- 1R01HD055651-01
- Acronym
- Microarray
- Status last verified
- Aug 2012
- First submitted
- 19 Jul 2010
- Last updated
- 22 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012 Dec 6;367(23):2175-84. doi: 10.1056/NEJMoa1203382.
PubMed 23215555
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis
- ClinicalTrials.gov ID
- NCT01279733
- Acronym / sponsor ID
- Microarray / AAAC8036
- Conditions
- Genetic Diseases
- Keywords
- microarray
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 4,450 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Oct 2008
- Primary completion
- Oct 2011 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 19 Jan 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 main objective of the multi-centered collaborative study is to evaluate the accuracy, efficacy and clinical advantages of prenatal diagnosis using microarray analysis as compared with conventional karyotyping.
Detailed description
Specifically, the aims are as follows:
- Demonstrate the performance of microarray analysis as a clinical method for prenatal cytogenetic diagnosis with regard to:
- Accuracy in the detection of the common autosomal and sex chromosomal aneuploid (trisomies, 13,18,21, 45,X, 47,XXY, etc.)
- Ability of microarray to diagnose less common, but clinically significant, cytogenetic aneusomies (e.g. DiGeorge, Williams, Smith- Magenis, Prader-Willi syndrome, etc.) currently not detected by conventional karyotype.
- Evaluation of the utility of microarray in specific clinical scenarios such as ultrasound detection of congenital anomalies and fetal growth disorders.
- Evaluate the appropriate construction of prenatal diagnostic microarray devices to allow maximal detection of clinically relevant information with minimal detection of unexpected and difficult to interpret findings which have no clinical significance but might provoke patient anxiety.
- Evaluate the feasibility and cost-effectiveness of using microarrays as a primary prenatal diagnostic tool.
- Evaluate approaches to integrate microarray into clinical prenatal cytogenetic diagnostic practice.
- Develop a prenatal diagnostic tissue repository (TDR) to facilitate the further development of microarray technology. This will be used to investigate the molecular etiologies of specific fetal anomalies and to test newer technologies, such as higher resolution microarrays.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Microarray Analysis | – | Genetic: Microarray analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 4,400 prenatal diagnostic samples will be obtained from patients undergoing prenatal testing for standard indications. Patients will be recruited at participating prenatal diagnostic centers by designated study personnel; recruitment of patients will be initiated as a pilot study. These patients will not contribute to the final planned sample size of 4400 patients. Two sub-studies will then be initiated consisting of 250 (or more) patients enrolled with sufficient amniotic fluid sample and 250 (or more) patients with sufficient villus sample.
Key inclusion criteria (4 listed)
- Singleton pregnancy having either chorionic villus sampling in the first trimester or an amniocentesis procedure at or after 16 weeks of gestation performed for prenatal cytogenetic diagnosis
- Karyotyping to be performed at Genzyme Genetics Cytogenetics Laboratory
- Trained study personnel available
- Presenting at pre-specified sites using Genzyme Genetics for routine prenatal diagnostic services
Key exclusion criteria (4 listed)
- Unavailability of one or both biologic parents to provide blood sample (e.g. egg or sperm donor, non-paternity)
- Patient refusal to allow follow-up through the neonatal period and up to age two if selected
- Participation in the study in a previous pregnancy
- Insufficient sample for microarray assay
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 |
|---|---|---|
| Microarray analysisMicroarray performed on prenatal specimen: Fluorescence in-situ hybridization (FISH) or other standardized tests such as qPCR or MLPA will be performed on the fetal sample to confirm abnormal MA findings of known and unknown clinical significance which are discordant with CC findings, including anomalies normally detected by karyotyping. Microarray analysis of DNA from parental blood samples will be used to determine whether CNVs detected in a fetal sample are also present in a healthy parent, in which case no further evaluation will take place, moreover any finding in a fetus which is duplicated in a parental microarray is considered to be confirmed. | Genetic | Microarray Analysis |
Primary outcome
Detection rate of fetal cytogentic abnormalites between microarray copy number analysis and karyotype in prenatal samples
Time frame: Up to 2.5 years after recruitment of 4400 patients.
This is a blinded prospective comparison of microarray copy number analysis to metaphase karyotyping for the detection of common fetal cytogentic abnormalites
2 secondary outcomes
The ability of microarray copy number analysis to identify clinically significant microdeletions and duplications not seen by standard karyotyping
Time frame: Up to 2.5 years .
The rates of clinically significant copy number variants associated with specific prenatal conditions
Time frame: Up to 2.5 years after recruitment of 4400 patients.
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 22 Aug 2012.
- Derived from this study: PubMed 23215555Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012 Dec 6;367(23):2175-84. doi: 10.1056/NEJMoa1203382.
Related trials for Genetic Diseases
RecruitingObservational study
Genetic Analysis of Uncommon Disease Presentations in Non-US Populations
Undiagnosed Diseases, Rare Diseases
Active, not recruitingPhase 1/2
Gene Transfer Clinical Trial for Infantile and Late Infantile Krabbe Disease Treated Previously With HSCT
Krabbe Disease
RecruitingObservational study
Characterization of Patients With Uncommon Presentations and/or Uncommon Diseases Associated With the Cardiovascular System
Metabolic Disease, Obesity
Not yet recruitingPhase 3
Roflumilast Cream 0.3% for Moderate to Severe Atopic Dermatitis
Atopic Dermatitis, Atopic Dermatitis (AD)
RecruitingPhase 2
Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
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.
Ronald Wapner, MD principal investigator
Columbia University
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 Genetic Diseases, run by Columbia University at 1 site in United States.
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 4 inclusion and 4 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 22 Aug 2012. 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 United States. 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?
Detection rate of fetal cytogentic abnormalites between microarray copy number analysis and karyotype in prenatal samples (time frame: Up to 2.5 years after recruitment of 4400 patients.). 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 NCT01279733, 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 22 Aug 2012.