Clinical trial NCT03902353: Screening of Pulmonary Veino Occlusive Disease in Heterozygous EIF2AK4 Mutation Carriers
Official title: Screening of Pulmonary Veino Occlusive Disease in Heterozygous EIF2AK4 Mutation Carriers
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Mutation
Genetic Syndrome
Keywords: Pulmonary veino occlusive disease, pulmonary hypertension
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-04-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Evolution of characteristics of asymptomatic heterozyous EIF2AK4 mutation carriers and monitor these subjects' clinical, functional, biological, echocardiographic
timeFrame: 1 year
Secondary outcomes:
measure: 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
timeFrame: 1 year
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: David MONTANI
state: Krémlin Bicêtre
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: MONTANI David, PhD
role: STUDY_CHAIR
References:
citation: Lechartier B, Girerd B, Eyries M, Beurnier A, Humbert M, Montani D. Screening for pulmonary veno-occlusive disease in heterozygous EIF2AK4 variant carriers. Eur Respir J. 2022 Aug 18;60(2):2200760. doi: 10.1183/13993003.00760-2022. Print 2022 Aug. No abstract available.