ClinicalTrials.gov
ClinicalTrials.gov Menu

Epidemiology and Pathophysiological Mechanisms of HTAP in SS and SC Children in Martinique and Guadeloupe. (SAPOTILLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03368261
Recruitment Status : Completed
First Posted : December 11, 2017
Last Update Posted : December 11, 2017
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Pointe-a-Pitre

Brief Summary:

pulmonary arterial hypertension (PAH) has been reported with a prevalence of approximately 30% in adult sickle cell disease (SCD) patients, with an increased mortality in SCD patients with PAH, compared with those without PAH. The identification of several hemolysis biomarkers such as lactate dehydrogenase, bilirubin, reticulocytes or hemoglobin level, has clearly documented a link between hemolysis and PAH. However, other physiopathological mechanisms may be involved to explain PAH in these patients, such as pulmonary thromboembolism, pulmonary fibrosis or left heart diastolic and / or systolic dysfunction.

The investigators suggest studying HTAP in patient's presenting the most frequent both drepanocytic syndromes, SS and SC and homogeneous in their medical coverage and the association between HTAP risk and specific SCD complications.


Condition or disease Intervention/treatment Phase
Sickle Cell Disease Other: HTAP/ clinical complications in the sickle cell disease Not Applicable

Detailed Description:

The primary aim of this study is to estimate the prevalence and the incidence of PAH in a population of SCD children (SS, SC) with similar medical caring, aged from 8 to 16 years old.

Unlike the important number of studies in SCD adults, very few SCD children studies were performed. None of these studies reported the mortality rate associated with PAH in children although the literature reported a decrease of this morbid-mortality comparing different medical caring of the patients. The investigators hypothesized that physiopathological mechanisms responsible for PAH had to be different in SCD children compared with adults, as most degenerative processes had no time enough to appear during children's lives. At the inclusion in our study the diagnosis of PAH will be performed by transthoracic Doppler-echocardiograms in a group of 306 children (aged between 8 to 16 years old) with either SS or SC genotype with similar medical caring, to avoid a known selection bias. These patients will be followed during a 3 years longitudinal period. The occurrence of the clinical specific complications associated with SCD (acute chest syndrome, painful vaso occlusive crisis, septicemia and stroke) and the observed mortality rate of our children group, will be compared in patients groups stratified according to the occurrence of PAH. The expression of several molecular and cellular genetic biomarkers potentially associated with this complication will also be studied.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 185 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Epidemiology and Pathophysiological Mechanisms of Pulmonary Arterial Hypertension in SS and SC Children in Martinique and Guadeloupe.Three Years Follow up of a Cohort of Children Aged From 8 to 16 Years Old
Actual Study Start Date : January 11, 2010
Actual Primary Completion Date : October 2, 2013
Actual Study Completion Date : October 17, 2016


Arm Intervention/treatment
HTAP/ clinical complications in the sickle cell disease
Supply epidemiological data on this detected HTAP, and allow the characterization of the clinico-biological paintings and the mortality which are associated to them.
Other: HTAP/ clinical complications in the sickle cell disease
At the inclusion in our study the diagnosis of PAH will be performed by transthoracic Doppler-echocardiograms in a group of 306 children (aged between 8 to 16 years old) with either SS or SC genotype with similar medical caring, to avoid a known selection bias. These patients will be followed during a 3 years longitudinal period. The occurrence of the clinical specific complications associated with SCD (acute chest syndrome, painful vaso occlusive crisis, septicemia and stroke) and the observed mortality rate of our children group, will be compared in patients groups stratified according to the occurrence of PAH. The expression of several molecular and cellular genetic biomarkers potentially associated with this complication will also be studied.




Primary Outcome Measures :
  1. incidence of pulmonary arterial hypertension [ Time Frame: Through study completion, an average of 5 years ]
    The primary outcome of the present study is to estimate the incidence of pulmonary arterial hypertension documented by the presence of tricuspid regurgitation jet velocity of at least 2.5 ms-1 by Doppler echocardiographic assessment.


Secondary Outcome Measures :
  1. The association between PAH risk and specific SCD complications [ Time Frame: Through study completion, an average of 5 years ]

    To determine the association between PAH risk and specific SCD complications (painful crisis, acute chest syndrome, severe infectious events, stroke, cerebral vasculopathy), expression of molecular (pro-PBN, nitrite/ nitrate compounds, sVCAM-1, sICAM-1, S- and P-selectine, plasmatic hemoglobin, ET-1, CD40L), cellular (microparticles, hemorheological parameters) biomarkers, and genetic markers (alpha-globin, type 3 NOS, endothélin-1, ACVRL1, BMPR2, BMP6).

    To determine if PAH is a risk factor of the clinical complications cited previously above and of mortality.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   8 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • children aged between 8 to 16 years old,
  • SS homozygote or SC compound heterozygote, followed by the sickle cell centers of Guadeloupe and Martinique or by the pediatric department of the university hospital of Fort-de-France, identified by the systematic neonatal screening programs performed in Guadeloupe and Martinique or by other labeled centers, registered in the French medical social security national program, and for which the parental and the old children consent has been obtained.

Exclusion Criteria:

  • other hemoglobinopathies, chronic transfusion therapy programs or treatments which affected the expression of the biomarkers studied (unless hydroxyurea treatment),
  • recent blood transfusion or phlebotomies (less than 3 months);
  • patients not at steady state,
  • pregnancy or breast feeding,
  • refusal of parental and old children consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03368261


Locations
Martinique
Hospital University Center of Martinique
Fort-de-France, Martinique, 97261
Sponsors and Collaborators
Centre Hospitalier Universitaire de Pointe-a-Pitre
Investigators
Study Director: Maryse ETIENNE-JULAN, Doctor specializing in SCD Hospital University Center of Pointe-à-Pitre

Responsible Party: Centre Hospitalier Universitaire de Pointe-a-Pitre
ClinicalTrials.gov Identifier: NCT03368261     History of Changes
Other Study ID Numbers: RBM-PAP-2009/69
First Posted: December 11, 2017    Key Record Dates
Last Update Posted: December 11, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre Hospitalier Universitaire de Pointe-a-Pitre:
Pulmonary arterial hypertension
SCD
Epidemiology

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn