Screening of Pulmonary Veino Occlusive Disease in Heterozygous EIF2AK4 Mutation Carriers (DELPHI-4)

January 17, 2020 updated by: Assistance Publique - Hôpitaux de Paris
Pulmonary Veino Occlusive Disease (PVOD) is a rare form of pulmonary arterial hypertension, characterised by a poor prognosis. Recent studies demonstrated that heritable form of pulmonary veino occlusive diseaseis due to bi-allelic mutations in EIF2AK4 gene. heritable pulmonary veino occlusive disease is an autosomal recessive disease. In the french referal center of severe PH, ulmonary veino occlusive disease patients carriers of bi-allelic mutations in EIF2AK4 gene were identified. Genetic counselling in these families allowed to identified herozygous carriers of a single mutation in EIF2AK4 gene. However, to date, nothing is known about the risk of these persons of developping pulmonary diseases. It appears essential to determine the clinical, functional, echocardiographic and radiologics characteristics of these persons, and their risk of developping Pulmonary veino occlusive disease

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

the investigators will evaluate the subjects at inclusion after informed by a clinical evaluation (dyspnea assessed by New York Heart Association functional class (I-IV), signs of right heart failure), a 6min walk test, a Computerized Tomography scan of the chest, an electrocardiogram, an echocardiography , an abdomina ulstrasound, a Cardiopulmonary exercise testing, a lung function tests , arterial blood gases.

At one and two years, a phone call will be made to to participants evaluate dyspnea and intercurrent events in all subjects. In the presence of pulmonary veino occlusive diseaseis symptoms, a new evaluation will be proposed in order to confirm of not pulmonary veino occlusive diseaseis.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Not Applicable

Contacts and Locations

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

Study Locations

  • France
    • Krémlin Bicêtre
      • Le Kremlin-Bicêtre, Krémlin Bicêtre, France, 94270

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female adult (age ≥18 years of age at the date of inclusion),
  • With an identification of the presence of a mutation of the EIF2AK4 gene in the heterozygous state,
  • Having given free and informed consent.

Exclusion Criteria:

  • Minor (age <18 years),
  • Patient with known Pulmonary veino occlusive disease or Pulmonary arterial hypertension
  • Woman having started a pregnancy or breastfeeding
  • protected adult persons,
  • Persons deprived of their liberty,
  • People in emergency,
  • Those who refused or were unable to give informed consent,
  • Contraindication to the exercise test (acute coronary syndrome, syncope, tight stenotic valve disease ...) See the list of relative and absolute contraindications to the exercise test (chapter 6.2).
  • No affiliation to a social security scheme (beneficiary or beneficiary).

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

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Adults without diagnosis of PH
Adults without diagnosis of PH carrying an heterozygous EIF2AK4
Other: Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation.
will be performed : a clinical evaluation (dyspnea assessed by New York Heart Association functional class (I-IV), signs of right heart failure), a 6min walk test, a Computerized Tomography scan of the chest, an electrocardiogram, an echocardiography (measurement of the velocity of tricuspid regurgitation, measurement of Tricuspid Annular Plane Systolic Excursion (TAPSE) and Tei index, pericardial effusion, dilatation and hypertrophy of the right ventricle), an abdomina ulstrasound, a stress Test (ventilation oxygen peak and ventilation oxygen specific, minute ventilation, dead-space ventilation / dead space, ventilatory reserve, alveolar-arterial gradient, pulse oxygen, PaO2), a lung function tests and measurement of Diffusing capacity or transfer factor of the Lung for Carbon mOnoxide (DLCO) and Nitric Oxide (DLNO), and a blood sample.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evolution of characteristics of asymptomatic heterozyous EIF2AK4 mutation carriers and monitor these subjects' clinical, functional, biological, echocardiographic
Time Frame: 1 year
frequency of abnormalities observed
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
predictive factors of the occurrence of PVOD follow prospectively a cohort of asymptomatic heterozyous EIF2AK4 mutation carriers to determine predictive factors of the occurrence of VOD
Time Frame: 1 year
number of heterozygous EIF2AK4 mutation carriers who will develop Pulmonary Veno-Occlusive Disease
1 year

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Study Chair: MONTANI David, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 23, 2019

Primary Completion (Anticipated)

September 1, 2020

Study Completion (Anticipated)

September 1, 2021

Study Registration Dates

First Submitted

March 14, 2019

First Submitted That Met QC Criteria

April 1, 2019

First Posted (Actual)

April 4, 2019

Study Record Updates

Last Update Posted (Actual)

January 21, 2020

Last Update Submitted That Met QC Criteria

January 17, 2020

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • K180501J

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

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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