Screening of Pulmonary Veino Occlusive Disease in Heterozygous EIF2AK4 Mutation Carriers

Not Applicable

• Conditions: Genetic Syndrome; Mutation
• Interventions: Other: Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation.

• Registration Number: NCT03902353
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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

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 Timeline

• Study First Submitted: 2019-03-14
• Study First Submitted QC: 2019-04-01
• Study First Posted: 2019-04-04
• Status Verified: 2019-07
• Study Start: 2019-09-23
• Last Update Submitted: 2020-01-17
• Last Update Posted: 2020-01-21
• Primary Completion: 2020-09-01
• Study Completion: 2021-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adults without diagnosis of PH	Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation.	Adults without diagnosis of PH carrying an heterozygous EIF2AK4

Primary Outcome Measures

Name	Time	Method
Evolution of characteristics of asymptomatic heterozyous EIF2AK4 mutation carriers and monitor these subjects' clinical, functional, biological, echocardiographic	1 year	frequency of abnormalities observed

Secondary Outcome Measures

Name	Time	Method
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	1 year	number of heterozygous EIF2AK4 mutation carriers who will develop Pulmonary Veno-Occlusive Disease

Trial Locations

Locations (1)

David MONTANI; 🇫🇷 Le Kremlin-Bicêtre, Krémlin Bicêtre, France