Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis

Genetic Diseases Clinical Trial

— Microarray  

Official title:

Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01279733
• Other study ID #: AAAC8036
• Secondary ID: 1R01HD055651-01
• Status: Completed
• Phase: N/A
• First received: July 19, 2010
• Last updated: August 21, 2012
• Start date: October 2008
• Est. completion date: October 2011

Study information

• Verified date: August 2012
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical 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.

Description:

Specifically, the aims are as follows:

1. Demonstrate the performance of microarray analysis as a clinical method for prenatal cytogenetic diagnosis with regard to:

1. Accuracy in the detection of the common autosomal and sex chromosomal aneuploid (trisomies, 13,18,21, 45,X, 47,XXY, etc.)

2. 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.

3. Evaluation of the utility of microarray in specific clinical scenarios such as ultrasound detection of congenital anomalies and fetal growth disorders.

2. 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.

3. Evaluate the feasibility and cost-effectiveness of using microarrays as a primary prenatal diagnostic tool.

4. Evaluate approaches to integrate microarray into clinical prenatal cytogenetic diagnostic practice.

5. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4450
• Est. completion date: October 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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

2. Karyotyping to be performed at Genzyme Genetics Cytogenetics Laboratory

3. Trained study personnel available

4. Presenting at pre-specified sites using Genzyme Genetics for routine prenatal diagnostic services

Exclusion Criteria:

1. Unavailability of one or both biologic parents to provide blood sample (e.g. egg or sperm donor, non-paternity)

2. Patient refusal to allow follow-up through the neonatal period and up to age two if selected

3. Participation in the study in a previous pregnancy

4. Insufficient sample for microarray assay

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Genetic Diseases

Intervention

Genetic:
• Microarray analysis
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.

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 2.5 years after recruitment of 4400 patients.	No
Secondary	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	Up to 2.5 years .	No
Secondary	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.	Up to 2.5 years after recruitment of 4400 patients.	No