Long-term Comparative Cerebrovascular Outcome After Transplantation vs Standard Care in Sickle Cell Anemia

Sickle Cell Disease Clinical Trial

— DREPAGREFFE2  

Official title:

Long-term Comparative Cerebrovascular Outcome After Transplantation vs Standard Care in Children With Sickle Cell Anemia ( DREPAGREFFE-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05053932
• Other study ID #: DREPAGREFFE2
• Status: Recruiting
• Start date: October 7, 2022
• Est. completion date: June 2025

Study information

• Verified date: August 2023
• Source: Centre Hospitalier Intercommunal Creteil
• Contact: Camille JUNG, MD
• Phone: 01 57 02 22 68
• Email: camille.jung[@]chicreteil.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of the present observational study is to remotely reevaluate the cohort of 67 sickle cell patients with transcranial Doppler-detected cerebral vasculopathy included in the national "Sickle Cell Transplant" protocol and whose 1- and 3-year results were published in JAMA (Journal of the American Medical Association) in 2019 and in BHJ in 2020.

Description:

The present observational study has the objective to reevaluate at distance the cohort of 67 children with sickle cell anemia enrolled in the "Drepagreffe"trial because of cerebral vasculopathy detected by transcranial Doppler. Results at 1 and 3 years were reported in JAMA in 2019 in BHJ in 2020. This trial was the first worldwide prospective study comparing transplantation to standard care in sickle cell disease. Velocities were highly significantly more reduced with a higher proportion of patients with normalized velocities and better quality of life after transplantation than on standard care. Despite a trend to a better ischemic lesions outcome at 3 years, the difference was not significant and cognitive performances were not different between both groups. The biologic study only assessed at enrollment and 1-year showed lower levels of Ang-2 and HGF (hepatocyte growth factor) after transplant and a significant and independent association between Doppler normalization probability with low Ang-2 and BDNF (brain-derived neurotrophic factor) levels.The aim of the present study is to reassess at 9-10 years this cohort with grants allowing to reevaluate cognitive functioning and hypoxia/angiogenic factors not realized in the systematic cohort follow-up

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 67
• Est. completion date: June 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

Inclusion Criteria:

• Patient of legal age or minor who participated in the DREPAGREFFE research protocol [NCT 01340404] between December 2010 and June 2013,
• Having read and understood the information letter

Exclusion Criteria:

• Refusal to participate
• Patient deceased

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Brain Ischemia
• Cerebral Infarction
• Cerebral Ischemia
• Ischemia
• Sickle Cell Disease
• Stenosis

Intervention

Other:
• blood collection
blood collection

Locations

Country	Name	City	State
France	Groupe hospitalier Pellegrin	Bordeaux
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Hôpital Henri Monr - APHP	Créteil
France	CHU de la Guadeloupe	La Guadeloupe
France	Hôpital Bicêtre AP-HP	Le Kremlin-Bicêtre
France	CHU de Lyon	Lyon
France	IHOPe	Lyon
France	Hôpital de la Timone	Marseille
France	CHU de Montpellier	Montpellier
France	Hôpital Necker - AP-HP	Paris
France	Hôpital Robert Debré AP-HP	Paris	IDF
France	CH de Pau	PAU
France	CHU de Rennes	Rennes
France	Hôpital Hautepierre	Strasbourg

Sponsors (3)

Lead Sponsor	Collaborator
Centre Hospitalier Intercommunal Creteil	Centre National de la Recherche Scientifique, France, Etablissement Français du Sang

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long term evolution (at 9-10 years) of Ischemic lesion on brain magnetic resonance imaging 10-year measurement of ischemic lesion on magnetic resonance imaging	The MRI-scores, ranging from 0 (best outcome) to 10 (worst outcome), are obtained by adding up the ischemic lesion scores from the left and right sides, i.e., 3 for territorial or 2 for border zone (cortical and subcortical), 1 for white matter and 1 for basal ganglia infarcts and 0 if absent on each side.	within 6 months of inclusion
Primary	Long term evolution (at 9-10 years) of arterial stenosis on cerebral and cervical magnetic resonance angiography	The MRA stenosis-scores, ranging from 0 (best outcome) to 32 (worst outcome) are defined as the weighted sums over the 8 assessed cerebral arteries, as 0 if no stenosis, 1 if mild stenosis (25-49%), 2 if moderate stenosis (50-74%), 3 if severe stenosis (75-99%), and 4 if occlusion.	within 6 months of inclusion
Secondary	Long term evolution (at 9-10 years) of cognitive performance	Full Scale Intelligence Quotient (40= worst outcome, 160= best outcome) is measured by Wechsler Intelligence Scale for Children -Fourth Edition (WISC-4) for children 7-16 years of age and by WAIS-3 (Weschler Adult Intelligence Scale-3) for patients older than 16 years	within 6 months of inclusion
Secondary	Long term evolution (at 9-10 years) of quality of life	Quality of life assessment is collected using the French version of the Pediatric Quality of Life Inventory Generic Core Scale (PedsQLTM 4.0 generic core scales) (physical, emotional, social, school items) (0= worst outcome, 100= best outcome) via self-report and parent proxy-report	within 6 months of inclusion
Secondary	Evolution at 9-10 years of factors of hypoxia and oxidative stress	Assessment on plasma Phosphatidyl-serine expression VEGF, Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2),EPO, HIF-1, BDNF, PDGF-AA	within 6 months of inclusion