MutationDELPHI-4NCT03902353
Screening of Pulmonary Veino Occlusive Disease in Heterozygous EIF2AK4 Mutation Carriers
A study testing Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation. in people with Mutation and Genetic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mutation, Genetic Syndrome
- What is being tested?
- Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 23 Sep 2019to 1 Sep 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
Show all 9Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
David MONTANI
Le Kremlin-Bicêtre, Krémlin Bicêtre, 94270
David MONTANI, MD, 01.45.21.79.76, david.montani@aphp.fr
Marc HUMBERT, PhD, 01.45.21.79.76, marc.humbert@aphp.fr
About this study
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
Read the 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.
- Conditions
- Mutation, Genetic Syndrome
- Being tested
- Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation.
- Keywords
- Pulmonary veino occlusive disease, pulmonary hypertension
- Medical subject headings
- Genetic Diseases, Inborn, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| Adults without diagnosis of PH | Other | Adults without diagnosis of PH carrying an heterozygous EIF2AK4 Receives: Other: Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evolution of characteristics of asymptomatic heterozyous EIF2AK4 mutation carriers and monitor these subjects' clinical, functional, biological, echocardiographic
frequency of abnormalities observed
Measured: 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
number of heterozygous EIF2AK4 mutation carriers who will develop Pulmonary Veno-Occlusive Disease
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2019
- Study start23 Sep 2019
- Primary completion1 Sep 2020 (estimated)
- Study completion1 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MutationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MONTANI David, PhD, Study chair, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03902353
- Sponsor's protocol ID
- K180501J
- Acronym
- DELPHI-4
- Status last verified
- Jul 2019
- First submitted
- 14 Mar 2019
- Last updated
- 21 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35710265
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Screening of Pulmonary Veino Occlusive Disease in Heterozygous EIF2AK4 Mutation Carriers
- ClinicalTrials.gov ID
- NCT03902353
- Acronym / sponsor ID
- DELPHI-4 / K180501J
- Conditions
- Mutation, Genetic Syndrome
- Keywords
- Pulmonary veino occlusive disease, pulmonary hypertension
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 23 Sep 2019 (actual)
- Primary completion
- 1 Sep 2020 (estimated)
- Study completion
- 1 Sep 2021 (estimated)
- First posted
- 4 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adults without diagnosis of PH | Other | Other: Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation.Adults without diagnosis of PH carrying an heterozygous EIF2AK4 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (9 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Other | Adults without diagnosis of PH |
Primary outcome
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 secondary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
- Derived from this study: PubMed 35710265Lechartier 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MONTANI David, PhD study chair
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Screening of adult without diagnosis of PH carrying an heterozygous EIF2AK4 mutation. in people with Mutation and Genetic Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact MONTANI David, PhD (01.45.21.79.76, david.montani@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evolution of characteristics of asymptomatic heterozyous EIF2AK4 mutation carriers and monitor these subjects' clinical, functional, biological, echocardiographic (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03902353, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2020.