Clinical trial NCT01279733: Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis
Official title: Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Genetic Diseases
Keywords: microarray
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2011-01-19
Enrollment: 4450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Detection rate of fetal cytogentic abnormalites between microarray copy number analysis and karyotype in prenatal samples
timeFrame: Up to 2.5 years after recruitment of 4400 patients.
Secondary outcomes:
measure: The ability of microarray copy number analysis to identify clinically significant microdeletions and duplications not seen by standard karyotyping
timeFrame: Up to 2.5 years .
measure: The rates of clinically significant copy number variants associated with specific prenatal conditions
timeFrame: Up to 2.5 years after recruitment of 4400 patients.
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Ronald Wapner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.