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Genomic Sequencing and Personalized Treatment for Birth Defects in Neonatal Intensive Care Units

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ClinicalTrials.gov Identifier: NCT02551081
Recruitment Status : Recruiting
First Posted : September 16, 2015
Last Update Posted : October 30, 2018
Sponsor:
Collaborators:
Xiamen Children's Hospital, Fujian of China
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Second Affiliated Hospital of Wenzhou Medical University
Maternal and Child Health Hospital of Hubei Province
The Maternal & Children Health Hospital of Dehong, Yunnan of China
Information provided by (Responsible Party):
Children's Hospital of Fudan University

Brief Summary:
The purpose of study is to evaluate the benefits of using the Next Generation Sequencing Technology to diagnose birth defects and genetic diseases. The results from genomic sequencing can also significantly shorten the time of examination, improve the diagnosis rate, guide the clinical treatments. So the ultimate goal is individualized or personalized therapy and promote prognosis.

Condition or disease
Genetic Disease Multiple Malformation Congenital Malformation

Detailed Description:

Neonatal congenital malformation is one of the most frequent cause of infant death in the western world and major cities of China. There are many different types of congenital malformations, and some of these can be caused by changes in gene mutation. Next generation sequencing (NGS) is a high-throughput parallel sequencing that can provide genetic information with high accuracy. It is a faster and cost-effective method to detect gene mutations compared to Sanger sequencing. We hope to couple genomic techniques with more traditional methods involved in genetic discovery in order to investigate a broad range of conditions for which there is strong evidence that genetic factors are involved. So In this study, we evaluated the clinical role of NGS testing for neonatal genetic disease in newborns compared to Sanger sequencing to observe whether this new technology can significantly shorten the time of examination, improve the diagnosis rate, guide the intervention treatments and promote prognosis.

These neonates who have an undiagnosed illness, and partial families, will be eligible to participate in the study. The study population will be recruited from Children's Hospital of Fudan University inpatient population, primarily the neonatal intensive care unit (NICU), with a subpopulation presenting to other hospitals in China. All affected study participants will receive a genetic screening according to their clinical symptom. All subjects will have blood drawn for DNA isolation and genomic sequencing at the time of enrollment in the study. All blood sample volumes will adhere to the Fudan procedure on maximum blood in pediatric patients. In addition, cerebrospinal fluid and tissue samples may be collected and stored in the bank of biosamples. DNA will be isolated and prepared for NGS or Sanger with Fudan protocols at the Translational Medicine Center of Children's Hospital of Fudan University. Partial familial samples will also be obtained, and nucleic acids will also be sequenced, as indicated, to assist in diagnosis of the genetic disease in the newborn. All sequencing data will be stored in the Genome Center Biorepository. In the case of positive study findings that may be diagnostic, our investigator will perform confirmatory clinical diagnostic testing and, if confirmed, a standard clinical diagnostic report will be placed in the patient's medical record. Follow up with the patient's family will be guided by the clinical care team. Both molecular diagnoses results and duration to diagnosis will be recorded as primary outcomes.

In addition, this information will help alleviate anxiety on the part of the family, and also provides a mechanism for patient crossover into the rapid NGS arm if the patient is clinically deteriorating, and at the clinical care team's request. Each time a study participant is enrolled, the clinician and parents will be asked to fill out a survey prior to NGS testing and after return of results. We will also review the patient's medical record and collect clinical variables including laboratory testing, radiology results, medications and other treatments received to further analyze the effect NGS has on clinical care. So the ultimate goal is individualized or personalized therapy. We plan to follow up with families annually up to 18 months post enrollment and record clinical outcomes related to this study.


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Study Type : Observational
Estimated Enrollment : 2000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Genomic Sequencing and Personalized Treatment for Birth Defects in Neonatal Intensive Care Units
Actual Study Start Date : October 1, 2015
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : December 30, 2020

Group/Cohort
Birth Defects
Neonates were diagnosed as birth defects who were recieving genomic sequencing and personalized treatment in NICU.



Primary Outcome Measures :
  1. Mortality [ Time Frame: At corrected age of 18 months ]
    The relative frequency of deaths in each group.

  2. Disability Rate [ Time Frame: At corrected age of 18 months ]
    Disability, defined as a physical or mental handicap, especially one that prevents a person from living a full, normal life or from holding a gainful job.

  3. Gene Mutation [ Time Frame: In 30 days after receipt of the sample ]
    To detect the mutation and characterize the genetic architecture and risk variants of neonatal malformation using different genomic methods.


Secondary Outcome Measures :
  1. Neurodevelopment(Bayley Scores) [ Time Frame: At corrected age of 18 months ]
    To evaluate neurodevelopmental function by Bayley Scores of Infant Development Mental Development Index (MDI), gain Incidence of MDI<70(Severe) or MDI<85(Moderate)

  2. Respiratory Support [ Time Frame: In 14 days after results disclosure ]
    To observe whether the clinical mornitoring will be changed after results disclosure

  3. Care Level [ Time Frame: In 14 days after results disclosure ]
    To observe whether the care level will be changed after results disclosure


Other Outcome Measures:
  1. The total cost for hospitalization [ Time Frame: At corrected age of 18 months ]
    Determination of utilization of healthcare resources in hospital charges in both arms.

  2. Average days of hospitalization [ Time Frame: At corrected age of 18 months ]
    From hospital to discharge.

  3. Parents' understanding of study results [ Time Frame: At corrected age of 3 months ]
    Assessed in parent surveys via questions assessing: subjective understanding, importance of understanding.

  4. Parents' recall of study results [ Time Frame: At corrected age of 3 months ]
    Assessed in parent surveys via questions assessing: results recall



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 28 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The study population will be recruited from Hospital inpatient population, primarily the neonatal intensive care unit who has some anomaly or abnormal laboratory testing suggestive of a genetic disease.
Criteria

Inclusion Criteria:

One of the following criteria required.

  1. Neonates admitted to the Neonatal Intensive Care Units in one of the study hospitals
  2. Clinical genetic testing or a genetic consult is ordered
  3. Subject has one major structural anomaly or three or more minor anomalies
  4. Abnormal laboratory testing suggestive of a genetic disease
  5. Abnormal response to standard therapy for a major underlying condition

Exclusion Criteria:

  1. Previously performed exome/genome sequencing on patient
  2. Any infant in which clinical considerations preclude drawing 1.0 ml of blood
  3. Has features pathognomonic for a large chromosomal aberration (Trisomy 13, 18, 21 or other)
  4. Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
  5. Parents refuse consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02551081


Contacts
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Contact: Wenhao Zhou, Doctor zwhchfu@126.com
Contact: Guoqiang Cheng, Doctor gqchengcm@163.com

Locations
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China, Shanghai
Children Hospital of Fudan University Recruiting
Shanghai, Shanghai, China
Contact: Wenhao Zhou, Doctor    (+86)021-64931003    zwhchfu@126.com   
Sponsors and Collaborators
Children's Hospital of Fudan University
Xiamen Children's Hospital, Fujian of China
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Second Affiliated Hospital of Wenzhou Medical University
Maternal and Child Health Hospital of Hubei Province
The Maternal & Children Health Hospital of Dehong, Yunnan of China
Investigators
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Study Chair: Wenhao Zhou, Doctor Children's Hospital of Fudan University

Additional Information:
Publications:
Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, Baker M, Ballow M, Bartoshesky LE, Bonilla FA, Brokopp C, Brooks E, Caggana M, Celestin J, Church JA, Comeau AM, Connelly JA, Cowan MJ, Cunningham-Rundles C, Dasu T, Dave N, De La Morena MT, Duffner U, Fong CT, Forbes L, Freedenberg D, Gelfand EW, Hale JE, Hanson IC, Hay BN, Hu D, Infante A, Johnson D, Kapoor N, Kay DM, Kohn DB, Lee R, Lehman H, Lin Z, Lorey F, Abdel-Mageed A, Manning A, McGhee S, Moore TB, Naides SJ, Notarangelo LD, Orange JS, Pai SY, Porteus M, Rodriguez R, Romberg N, Routes J, Ruehle M, Rubenstein A, Saavedra-Matiz CA, Scott G, Scott PM, Secord E, Seroogy C, Shearer WT, Siegel S, Silvers SK, Stiehm ER, Sugerman RW, Sullivan JL, Tanksley S, Tierce ML 4th, Verbsky J, Vogel B, Walker R, Walkovich K, Walter JE, Wasserman RL, Watson MS, Weinberg GA, Weiner LB, Wood H, Yates AB, Puck JM, Bonagura VR. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014 Aug 20;312(7):729-38. doi: 10.1001/jama.2014.9132. Erratum in: JAMA. 2014 Nov 26;312(20):2169. Bonagura, Vincent R [Added].

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Children's Hospital of Fudan University
ClinicalTrials.gov Identifier: NCT02551081     History of Changes
Obsolete Identifiers: NCT02607189
Other Study ID Numbers: CHFudanU_NNICU2
First Posted: September 16, 2015    Key Record Dates
Last Update Posted: October 30, 2018
Last Verified: October 2018
Additional relevant MeSH terms:
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Congenital Abnormalities
Genetic Diseases, Inborn