Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Non Invasive Prenatal Testing (NIPT) of Single-gene Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02339402
Recruitment Status : Unknown
Verified January 2017 by Maastricht University Medical Center.
Recruitment status was:  Recruiting
First Posted : January 15, 2015
Last Update Posted : January 13, 2017
Sponsor:
Collaborator:
Radboud University
Information provided by (Responsible Party):
Maastricht University Medical Center

Tracking Information
First Submitted Date January 12, 2015
First Posted Date January 15, 2015
Last Update Posted Date January 13, 2017
Study Start Date June 2014
Estimated Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 14, 2015)
Development of a targeted molecular test (mostly standard PCR or real-time PCR) for non-invasive prenatal testing of single-gene disorders. [ Time Frame: 2014-2016 ]
Main aims are to
  1. demonstrate the presence or absence of (a) mutant allele(s) in maternal plasma
  2. examine if there is a sufficient concentration of fetal nucleic acids in the maternal plasma to reliably diagnose the monogenic disorder
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT02339402 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Non Invasive Prenatal Testing (NIPT) of Single-gene Disorders
Official Title NON-INVASIVE PRENATAL TESTING (NIPT) OF FETAL SINGLE-GENE DISORDERS IN MATERNAL BLOOD
Brief Summary Developing a new non-invasive prenatal test for single gene disorders from cell free fetal DNA, retrieved from the mothers blood.
Detailed Description

Rationale: Conventional prenatal diagnosis (PND) for single-gene disorders requires invasive procedures, either chorionic villus sampling between 11 and 14 weeks gestation or amniocentesis after 15 weeks. Although these approaches to obtain foetal DNA currently provide the golden standard for PND, the invasive procedures carry a risk of miscarriage of 0.5-1%. A reliable non-invasive alternative has long been sought. Circulating cell-free foetal (cff) nucleic acids (DNA and RNA), which are present in maternal blood during pregnancy, can be used for non-invasive prenatal testing (NIPT). NIPT for some chromosomal anomalies (trisomy 21, 13, 18) is now validated. NIPT for other chromosomal anomalies is still under development. NIPT of single-gene disorders is technically very challenging, due to the predominance of maternal DNA sequences, Some small studies have shown that a very limited number of monogenic genetic disorders can currently be diagnosed in maternal blood. In general de novo mutations in the foetus and paternally transmitted disorders are less difficult to diagnose than maternally transmitted disorders.

In this study, the investigators aim to develop non-invasive targeted molecular analysis using cell free fetal (cff) DNA and cff RNA for single-gene disorders, in pregnant women referred to the departments of Clinical Genetics of Maastricht University Medical Centre (MUMC+) and Radboud University Medical Centre (RUMC) for conventional PND. The investigators will contribute to literature by confirming earlier published results, and by adding other single-gene disorders or mutations to the list of disorders for which the possibility of the use of cff DNA will be examined.

Objective: Developing targeted non-invasive prenatal analysis for single-gene disorders using cff DNA and RNA in maternal plasma.

Study design: This study is a proof of concept study in which we aim to demonstrate that molecular analysis can indicate the presence or absence of (a) mutant allele(s) in maternal plasma.

Study population: Pregnant women (≥18y) referred to the Department of Clinical Genetics of MUMC+ or RadboudUMC for conventional PND, for one of the following reasons:

  • The fetus is at high risk of having inherited a dominant or recessive disorder of his/her affected parent(s).
  • The fetus at risk of having a de novo disorder on the basis of ultrasonography findings.

Main study endpoints: Does targeted molecular analysis of cff DNA and RNA indicate

  1. the presence or absence of (a) mutant allele(s) in maternal plasma
  2. the presence of a sufficient concentration of foetal nucleic acids in the maternal plasma to reliably diagnose the monogenic disorder Nature and extent of the burden and risks associated with participation and benefit: minimal burden: one moment of blood sampling for the pregnant woman and her partner. In most cases the blood sampling will be combined with regular blood sampling. Benefit: no benefit for this pregnancy as in the study phase the result of the invasive prenatal test is leading.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Foetal DNA is isolated from the blood of pregnant women and their partners
Sampling Method Probability Sample
Study Population

Pregnant women and their partner (≥18y) that undergo an invasive procedure for prenatal genetic diagnosis in the MUMC+ of RUMC for one of the following indications:

  • fetus at high risk of having inherited a dominant or recessive disorder of his/her affected parent(s) or
  • fetus at risk of having a de novo disorder on the basis of ultrasonography findings.
Condition Hereditary Disease
Intervention Not Provided
Study Groups/Cohorts Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: January 12, 2017)
160
Original Estimated Enrollment
 (submitted: January 14, 2015)
90
Estimated Study Completion Date May 2018
Estimated Primary Completion Date January 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • the pregnant woman is scheduled for or has recently undergone invasive prenatal testing (regular care) because of one of the following reasons:

    • the fetus is at high risk of a having inherited a single-gene disorder from his/her affected parent(s).
    • the fetus is at risk of having a de dominant novo disorder on the basis of ultrasonography findings.
  • the pregnant woman is 18 years or older
  • the pregnant woman has sufficient understanding of Dutch language and is able to give informed consent

Exclusion Criteria:

  • if in the opinion of the treating physician psychological distress is so severe that asking for participation is not safe
  • the pregnant woman is treated for a malignancy
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number NCT02339402
Other Study ID Numbers NL48304/METC azM/UM 14-02-012
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Maastricht University Medical Center
Study Sponsor Maastricht University Medical Center
Collaborators Radboud University
Investigators
Principal Investigator: Christine de Die, MD PhD Maastricht UMC
PRS Account Maastricht University Medical Center
Verification Date January 2017