Screening of Pulmonary Veino Occlusive Disease in Heterozygous EIF2AK4 Mutation Carriers

NCT03902353 | Unknown

• 1 other identifier: K180501J
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Mutation; Genetic Syndrome

Keywords

Pulmonary veino occlusive disease, pulmonary hypertension

Outcome Measures

Primary Outcomes (1)

• Evolution of characteristics of asymptomatic heterozyous EIF2AK4 mutation carriers and monitor these subjects' clinical, functional, biological, echocardiographic

  frequency of abnormalities observed

  1 year

Secondary Outcomes (1)

• 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

Study Arms (1)

Adults without diagnosis of PH

OTHER

Adults without diagnosis of PH carrying an heterozygous EIF2AK4

Other: Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation.

Interventions

Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation. OTHER

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.

Adults without diagnosis of PH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• With an identification of the presence of a mutation of the EIF2AK4 gene in the heterozygous state,
• Having given free and informed consent.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

David MONTANI

Le Kremlin-Bicêtre, Krémlin Bicêtre, 94270, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 35710265 DERIVED

MeSH Terms

Conditions

Genetic Diseases, Inborn; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• MONTANI David, PhD

  Assistance Publique - Hôpitaux de Paris

  STUDY CHAIR

Central Study Contacts

MONTANI David, PhD

CONTACT

01.45.21.79.76; david.montani@aphp.fr

GIRERD Barbara, MPCG, PhD

CONTACT

01 45 21 79 72; barbara.girerd@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: April 4, 2019
• Study Start: September 23, 2019
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2021
• Last Updated: January 21, 2020

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)