Expanded Noninvasive Genomic Medical Assessment: The Enigma Study

NCT02787486 | Completed

• 1 other identifier: PRO-102-ENIGMA
• Study Type: observational
• Target: 760
• Locations: 1 country
• Sites: 8

Brief Summary

In January 2007, the American Congress of Obstetricians and Gynecologists (ACOG) revised its guidelines that now recommend physicians are ethically obligated to fully inform all pregnant women that screening for fetal chromosomal abnormalities including biochemical screening tests and invasive procedures such as CVS or amniocentesis is available, regardless of age. Further, it is entirely up to the patient to decide whether or not she wishes to be screened for fetal chromosomal abnormalities without judgment from the physician. Noninvasive laboratory-developed tests (LDTs) that detect an abnormal amount of maternal and fetal DNA in an expectant mother's blood sample (known as circulating cell-free DNA) are now available. These LDTs have not been cleared or approved by the U.S. Food and Drug Administration (FDA). Although LDTs to date have not been subject to U.S. FDA regulation, certification of the laboratory is required under the Clinical Laboratory Improvement Amendments (CLIA) to ensure the quality and validity of the test. To sample collection study will obtain whole blood specimens from pregnant subjects to be used for development of prenatal assays to assist in the screening for fetal genetic abnormalities, infectious and other diseases, and blood group typing through detection of circulating cell-free DNA extracted from maternal plasma.

Conditions

Down Syndrome; Edwards Syndrome; Patau Syndrome; Klinefelter Syndrome; Turner Syndrome; DiGeorge Syndrome; Chromosome Deletion; Aneuploidy

Keywords

Down syndrome; Edwards syndrome; Patau syndrome; Klinefelter syndrome; DiGeorge syndrome; Chromosome Deletion; Aneuploidy

Outcome Measures

Primary Outcomes (1)

• Point estimates and 95% CIs for sensitivity, specificity, PPV, and NPV versus birth outcome (trisomy or Unaffected/non-trisomy) for the LDT in the population of pregnancies at mixed-risk for chromosomal abnormalities

  Primary Objective

  about 3 years

Secondary Outcomes (1)

• To estimate the false positive rate of the LDT versus birth outcome (trisomy or Unaffected/ non-trisomy) in a low-risk sub-population of pregnant women undergoing serum biochemical screening for fetal aneuploidy.

  about 3 years

Study Arms (2)

Aneuploidy Arm

Includes pregnant women at high risk for fetal chromosome aneuploidy for serum screening

Other: Blood sampling for Laboratory Developed Test (LDT) analysis

TORCH Arm

Infectious disease arm: Toxoplasmosis, other viruses, rubella, cytomegalovirus, and herpes simplex virus (TORCH). Includes pregnant women at low-risk for fetal aneuploidy that may be at increased risk for fetal infection for serum screening

Other: Blood sampling for Laboratory Developed Test (LDT) analysis

Interventions

Blood sampling for Laboratory Developed Test (LDT) analysis OTHER

Each enrolled subject, either in the first or second trimester, will donate up to 50 mL (just over 3 tablespoons) of whole blood for development of the LDT

Aneuploidy Arm; TORCH Arm

Eligibility Criteria

• Age: 18 Years - 54 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

All pregnant women undergoing standard maternal serum screening for fetal aneuploidy will be considered for enrollment as well as those with a priori risk factors for fetal aneuploidy.

You may qualify if:

• Subject is willing to provide informed consent and comply with study procedures
• Pregnant female, 18 to 54 years of age carrying a singleton fetus of 8 to 22 weeks gestational age
• Willing to provide a study blood sample in accordance with the protocol
• Willing to allow access to her medical records to collect pregnancy outcome information
• Willing to provide consent for release of fetal karyotype if an invasive procedure (CVS or amniocentesis) is performed during the pregnancy
• Subject is known to be at risk for one or more of the following:
• fetal gene and chromosome abnormalities (e.g., T21, T18, T13, microdeletion syndromes, sex chromosome abnormalities)
• congenital fetal infection (e.g. toxoplasmosis, syphilis, HIV, rubella, CMV, HSV)
• irregular blood group antigens (subject or father of the baby)
• other condition amenable to noninvasive prenatal testing such as a single gene disorder (e.g., CF, sickle cell, Fragile X)

You may not qualify if:

• No fetal heart activity detected
• Mother or father have known chromosomal abnormalities (including known balanced translocations)
• Women with active or history of malignancy

Sponsors & Collaborators

• Progenity, Inc.: lead

Study Sites (8)

Valley Perinatal

Scottsdale, Arizona, 85258, United States

Location

Heinen Obstectrics & Gynecology

Eunice, Louisiana, 70535, United States

Location

Newlife Wellness OBGYN

Brooklyn, New York, 11220, United States

Location

Lakeshore Women's Specialists

Mooresville, North Carolina, 28117, United States

Location

Cincinnati Obgyn

Cincinnati, Ohio, 45219, United States

Location

James D. Kasten, M.D., Inc.

Norwalk, Ohio, 44857, United States

Location

Regional Obstetrical Consultants

Chattanooga, Tennessee, 37403, United States

Location

Texas Maternal-Fetal Medicine

Webster, Texas, 77598, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Down Syndrome; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Klinefelter Syndrome; Turner Syndrome; DiGeorge Syndrome; Chromosome Deletion; Aneuploidy

Interventions

Blood Specimen Collection; Telbivudine

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Sex Chromosome Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Sex Chromosome Disorders; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Gonadal Dysgenesis; 22q11 Deletion Syndrome; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypoparathyroidism; Parathyroid Diseases; Monosomy; Chromosome Aberrations; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Peter Stiegler, PhD

  Head of Clinical Affairs

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: June 1, 2016
• Study Start: October 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: August 21, 2019

Record last verified: 2019-01

Locations

US (8)