Proteomic Profiling for Congenital Diaphragmatic Hernia (pro-CDH)

July 17, 2018 updated by: Centre Hospitalier Universitaire de Besancon

Proteomic Analysis of Amniotic Fluid in the Case of Diaphragmatic Hernia: Search for Prognostic Expression Profiles

Congenital diaphragmatic hernia (CDH) is a severe congenital malformation, related to a developmental defect of the diaphragm. The incidence of CDH is approximated at 1 in 3,000 live births. Although advances in surgery and neonatal intensive care have improved the prognosis, mortality remains high, around 30-50% related to severe lung hypoplasia and persistent pulmonary hypertension. Prenatal evaluation with observed/expected Lung over Head Ratio (o/e LHR), liver position and total lung volume measured by magnetic resonance, have been shown to correlate with neonatal mortality . However, the preponderant factor of persistent pulmonary hypertension remains difficult to predict prenatally. In patients with isolated diaphragmatic hernia (without associated malformations or karyotype abnormalities), prognosis is evaluated indirectly on pulmonary development from pulmonary volume measurements. Apart from the most caricatural cases with extremely good or very pejorative values, for a large proportion of fetuses with diaphragmatic dome hernia the prognosis remains uncertain.

The aim of the proposal is to investigate whether the analysis of the proteom of the amniotic fluid of the fetuses with CDH could give information of a prognostic character. The objective of the study is to identify, from the proteomic profile of the amniotic fluid of mothers whose fetus has CDH, prognostic markers candidates for death at 2 months of the infant. The first step is to carry out an exploratory and non-interventional study on a small sample (n = 10) of the target population. This is a preliminary step before considering, if the results are encouraging, a large-scale study from a biological collection to determine candidate proteins (new biomarkers) which relative expression levels could be used as surrogate marker of pulmonary hypoplasia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Pregnant patients for whom amniocentesis will be performed as part of the prenatal management of CDH confirmed by fetal ultrasound will be approached fot inclusion in the study. The indication of amniocentesis will be indicated according to the usual standards of care. Briefly, the study will not involve any additional invasive procedure. In our study, amniocentesis will be indicated during the conventional management of these patients. The needs of our research will not lead to additional amniocenteses, but simply an increase in the volume of amniotic fluid collected. An additional volume of 5 ml will be sampled for volumes usually taken from 20 to 30 ml. This volume of sampling will have a very limited impact on maternal and fetal well-being. An analysis of the proteom of the amniotic fluid of the patients will be carried out. The relative amounts of proteins and peptides contained in the amniotic fluid will be analyzed to explore variations in proteomic profile that may reflect different clinical gravity in terms of further evolution. The usual management of the patients and their children will not be modified by the procedures related to the research.

The first step will consist in carrying out a depletion of the major proteins, in particular albumin. A protein assay will be carried out from the same amount of protein for each sample (standardization). This depletion step will be followed by a migration step on a gel of 1D electrophoresis. Its purpose is both to eliminate all the contaminants that can hinder mass spectrometry analysis, to separate the proteins according to their molecular weight in order to simplify the protein mixture and to have a visual control of the heterogeneity of the sample. A differential visual analysis after staining will allow to define the highly variable zones between the groups of patients and within the same sample. We will select the zone of interest in identical manner for each sample and for the whole of the gel track. The use of commercial electrophoresis gels of the same batch and the parallel analysis of several samples of different groups and the use of quality controls ensure reproducibility. The proteins contained in these bands / gel zones are then digested according to a standardized protocol under controlled conditions. The simultaneous treatment of the different biological samples makes it possible to considerably reduce the impact of the variability of this step in the final differential statistical analysis. At the end of this step the proteins are analyzed by an LC-ESI MS / MS approach. This LC-ESI MS / MS approach consists of separating the peptides on a chromatographic separation column which is coupled directly to the ESI-MS / M mass spectrometer. This analytical approach can allow the identification of more than 1000 proteins and 5000 peptides. This analysis is repeated 3 times per sample so that analytical variability can be taken into account in differential statistical studies. At the end of this protocol the raw data of each zone are pooled by sample and the differential statistical study can be carried out.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • France
      • Besançon, France, 25000
        • Active, not recruiting
        • CHU de Besancon
      • Dijon, France, 21000

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Probability Sample

Study Population

Mothers whose fetus has CDH

Description

Inclusion Criteria:

Pregnant patients for whom amniocentesis will be performed as part of the prenatal diagnosis of a diaphragmatic hernia.

Exclusion Criteria:

  • Refusal of patients,
  • Refusal of spouse regarding data of the future child,
  • Multiple malformations,
  • Twin pregnancy,
  • Prenatal diagnosis of an unconfirmed diaphragmatic hernia,
  • Miscarriage after amniocentesis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
1
Mothers whose fetus has CDH

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Neonatal death
Time Frame: 2 months of age
2 months of age

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Prenatal death of the fetus
Time Frame: 9 months
Death during pregnancy
9 months
Neonatal death
Time Frame: 15 days
15 days
Apgar score
Time Frame: 5 min after birth
5 min after birth
Age at surgery
Time Frame: 6 months of age
6 months of age
Need for a diaphragmatic prosthesis
Time Frame: 6 months of age
6 months of age
Duration of ventilation (in days)
Time Frame: 6 months of age
6 months of age
Duration of the oxygen dependency (in days)
Time Frame: 6 months of age
6 months of age
Need of supplemental oxygen therapy
Time Frame: 28 days of age
Binary outcome (Yes/No)
28 days of age
Occurrence of pulmonary hypertension
Time Frame: 6 months of age
6 months of age
Duration of parenteral nutrition (in days)
Time Frame: 6 months of age
6 months of age
Age at the beginning of enteral nutrition
Time Frame: 6 months of age
6 months of age
Age at the beginning of oral nutrition
Time Frame: 6 months of age
6 months of age
Duration of hospital stay (in days)
Time Frame: 6 months of age
6 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Hospitalier Universitaire de Besancon

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
FEMTO-ST

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 18, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 16, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 7, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • API/2016/78

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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