Ignite Creation Date:
2024-05-05 @ 5:16 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00426686
Status:
COMPLETED
Last Update Posted:
2012-12-12
First Post:
2007-01-24
Brief Title:
ADAMTS13 in Thrombotic Thrombocytopenic Purpura
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
ADAMTS13-related Prognostic Factors in Adult and Pediatric Thrombotic Thrombocytopenic Purpura
Status:
COMPLETED
Status Verified Date:
2011-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ADAMTS13
Brief Summary:
Thrombotic thrombocytopenic purpura TTP is a thrombotic microangiopathy defined by the spontaneous formation of platelet thrombi in the microvessels These platelet microthrombi are responsible for a mechanical hemolytic anemia a thrombocytopenia and a multivisceral ischemia TTP is a rare but life-threatening disease in the absence of appropriate treatment PLASMATHERAPY The onset of the disease usually occurs in adulthood MOSCHCOVITZ syndrome and rarely in childhood UPSHAW-SCHULMAN syndrome TTP is either sporadic or recurrent with multiple unpredictable relapses TTP pathophysiology has remained obscure until a new metalloprotease ADAMTS13 has been demonstrated to be involved in about 90 of all cases Physiologically ADAMTS13 function consists in limiting the size of von Willebrand factor VWF multimers and consequently their hemostatic capacity A large majority of TTP is associated with a severe deficiency of ADAMTS13 In most cases ADAMTS13 severe deficiency is acquired via auto-antibodies to ADAMTS13 more rarely ADAMTS13 deficiency is hereditary via ADAMTS13 gene mutations ADAMTS13 auto-antibodies are either inhibitory of the catalytic activity or non inhibitory ADAMTS13 mutations are spread all over the gene
TTP prognosis is quite heterogeneous Indeed in about one third of the patients TTP is refractory to PLASMATHERAPY andor chronic relapsing Until now TTP prognosis factors are not known Their identification is however crucial both to adapt the curative treatment of an acute episode addition of first intention immunosuppressive agents to PLASMATHERAPY and to prevent relapses
In this context the aim of the current project is to identify some ADAMTS13 related prognosis factors in TTP A national prospective multicenter study including both adult and pediatric patients with TTP related to a severe ADAMTS13 deficiency will be designed over a three-year period This study will involve our group as the French reference center for ADAMTS13 and 10 clinical departments from various French hospitals Patients will be tested for ADAMTS13 activity and antigen ADAMTS13 antibodies and ADAMTS13 gene sequencing Our main hypothesis is that the inactivation of the ADAMTS13 domains crucial for its catalytic activity either by inhibitory auto-antibodies acquired TTP or by genetic mutations hereditary TTP is a major bad prognosis factor
TTP prognosis is quite heterogeneous Indeed in about one third of the patients TTP is refractory to PLASMATHERAPY andor chronic relapsing Until now TTP prognosis factors are not known Their identification is however crucial both to adapt the curative treatment of an acute episode addition of first intention immunosuppressive agents to PLASMATHERAPY and to prevent relapses
In this context the aim of the current project is to identify some ADAMTS13 related prognosis factors in TTP A national prospective multicenter study including both adult and pediatric patients with TTP related to a severe ADAMTS13 deficiency will be designed over a three-year period This study will involve our group as the French reference center for ADAMTS13 and 10 clinical departments from various French hospitals Patients will be tested for ADAMTS13 activity and antigen ADAMTS13 antibodies and ADAMTS13 gene sequencing Our main hypothesis is that the inactivation of the ADAMTS13 domains crucial for its catalytic activity either by inhibitory auto-antibodies acquired TTP or by genetic mutations hereditary TTP is a major bad prognosis factor
Detailed Description:
Thrombotic thrombocytopenic purpura TTP is a thrombotic microangiopathy defined by the spontaneous formation of platelet thrombi in the microvessels These platelet microthrombi are responsible for a mechanical hemolytic anemia a thrombocytopenia and a multivisceral ischemia TTP is a rare but life-threatening disease in the absence of appropriate treatment PLASMATHERAPY The onset of the disease usually occurs in adulthood MOSCHCOVITZ syndrome and rarely in childhood UPSHAW-SCHULMAN syndrome TTP is either sporadic or recurrent with multiple unpredictable relapses TTP pathophysiology has remained obscure until a new metalloprotease ADAMTS13 has been demonstrated to be involved in about 90 of all cases Physiologically ADAMTS13 function consists in limiting the size of von WILLBRAND factor VWF multimers and consequently their hemostatic capacity A large majority of TTP is associated with a severe deficiency of ADAMTS13 activity leading to the accumulation of ultra large VWF multimers in plasma inducing the formation of platelet microthrombi in the microcirculation In most cases ADAMTS13 severe deficiency is acquired via auto-antibodies to ADAMTS13 more rarely ADAMTS13 deficiency is hereditary via ADAMTS13 gene mutations ADAMTS13 auto-antibodies are either inhibitory of the catalytic activity or non inhibitory ADAMTS13 mutations are spread all over the gene
TTP prognosis is quite heterogeneous Indeed in about one third of the patients TTP is refractory to PLASMATHERAPY andor chronic relapsing Until now TTP prognosis factors are not known Their identification is however crucial both to adapt the curative treatment of an acute episode addition of first intention immunosuppressive agents to PLASMATHERAPY and to prevent relapses
In this context the aim of the current project is to identify some ADAMTS13 related prognosis factors in TTP A national prospective multicenter study including both adult and pediatric patients with TTP related to a severe ADAMTS13 deficiency will be designed over a three-year period This study will involve our group as the French reference center for ADAMTS13 and about 50 clinical departments from various French hospitals Patients will be tested for ADAMTS13 activity and antigen ADAMTS13 antibodies and ADAMTS13 gene sequencing Our main hypothesis is that the inactivation of the ADAMTS13 domains crucial for its catalytic activity either by inhibitory auto-antibodies acquired TTP or by genetic mutations hereditary TTP is a major bad prognosis factor
TTP prognosis is quite heterogeneous Indeed in about one third of the patients TTP is refractory to PLASMATHERAPY andor chronic relapsing Until now TTP prognosis factors are not known Their identification is however crucial both to adapt the curative treatment of an acute episode addition of first intention immunosuppressive agents to PLASMATHERAPY and to prevent relapses
In this context the aim of the current project is to identify some ADAMTS13 related prognosis factors in TTP A national prospective multicenter study including both adult and pediatric patients with TTP related to a severe ADAMTS13 deficiency will be designed over a three-year period This study will involve our group as the French reference center for ADAMTS13 and about 50 clinical departments from various French hospitals Patients will be tested for ADAMTS13 activity and antigen ADAMTS13 antibodies and ADAMTS13 gene sequencing Our main hypothesis is that the inactivation of the ADAMTS13 domains crucial for its catalytic activity either by inhibitory auto-antibodies acquired TTP or by genetic mutations hereditary TTP is a major bad prognosis factor
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None