ADAMTS13 in Thrombotic Thrombocytopenic Purpura

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00426686
First received: January 24, 2007
Last updated: December 11, 2012
Last verified: April 2011
  Purpose

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 and/or 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.


Condition
Thrombotic Thrombocytopenic Purpura

Study Type: Observational
Study Design: Observational Model: Case-Only
Official Title: ADAMTS13-related Prognostic Factors in Adult and Pediatric Thrombotic Thrombocytopenic Purpura

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Biospecimen Retention:   Samples With DNA

March 2010


Enrollment: 153
Study Start Date: November 2006
Study Completion Date: April 2011
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
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 and/or 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Adult and pediatric patients with TTP related to a severe ADAMTS13 deficiency.

Criteria

Inclusion Criteria:

  • clinical suspicion of TTP
  • Hemoglobin level < 10 g/dl (adult) or < 12 g/dl (child)
  • Platelet level < 150 giga/l
  • ADAMTS13 activity < 5%

Exclusion Criteria:

  • Cancer
  • Organ graft
  • HIV infection
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00426686

Locations
France
Hôpital Antoine Béclère
Clamart, France, 92140
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: paul COPPO, MD, PhD Hôpital Saint Antoire, PARIS
Study Director: Elie AZOULAY, MD, PhD Hôpital Saint Louis, PARIS
Study Director: Benoît SCHLEMMER, MD Hôpital Saint Louis, PARIS
Study Director: Eric OKSENHENDLER, MD Hôpital Saint Louis, PARIS
Study Director: Fadi FAKHOURI, MD Hôpital Necker, PARIS
Study Director: Jean-Paul MIRA, MD, PhD Hôpital Cochin, PARIS
Study Director: Eric RONDEAU, MD Hôpital Tenon, PARIS
Study Director: Jean-paul VERNANT, MD Hôpital la Pitié Salpétrière, PARIS
Study Director: Nicolas SCHLEINITZ, MD CHU Conception, MARSEILLE
Study Director: Gilles KAPLANSKI, MD, PhD CHU Conception, MARSEILLE
Study Director: Albert BENSMAN, MD Hôpital Trousseau, PARIS
Study Director: Chantal LOIRAT, MD Hôpital Robert Debré, PARIS
Study Director: Brigitte BADER-MEUNIER, MD Hôpital Robert Debré, PARIS
Study Director: Christophe PIGUET, MD Hôpital Dupuytren, LIMOGES
Study Director: Guy PUTET, MD Hospices civils de LYON, LYON
Study Director: Béatrice DUCOT, MD INSERM U569 Kremlin Bicêtre, Paris
Study Director: Agnes VEYRADIER, MD, PhD Hôpital Antoine Béclère, CLAMART
Study Director: Thierry LEBLANC, MD Hôpital Saint-Louis, PARIS
Study Director: Patrick NIAUDET, MD, PhD Hôpital Necker, PARIS
Study Director: Christophe RIDEL, MD Hôpital Tenon, PARIS
Study Director: Pascale POULLIN, MD CHU de la Conception, MARSEILLE
Study Director: arlos FRANGIE, MD Hôpital Bicêtre, LE KREMLIN BICETRE
Study Director: Hélène FRANCOIS, MD Hôpital Bicêtre, LE KREMLIN BICETRE
Study Director: Olivier LAMBOTTE, MD Hôpital Bicêtre, LE KREMLIN BICETRE
Study Director: Dominique BORDESSOULE, MD, PhD Hôpital Dupytren, LIMOGES
Study Director: Stéphane GIRAULT, MD Hôpital Dupytren, LIMOGES
Study Director: Hervé CHAMBOST, MD Hôpital de la Timone Enfants, Marseilles
Study Director: Pierre BORDOGONI, MD, PhD Hôpital de Brabois-Hôpital d'Enfants, Vandoeuvre-lès-Nancy
Study Director: Alexandra SALMON, MD Hôpital de Brabois- hôpital d'enfants, Vandoeuvre-lès-Nancy
Study Director: Laurence CLEMENT, MD Hôpital de Brabois-Hôpital d'enfants, Vandoeuvre-lès-Nancy
Study Director: Christian COMBE, MD, PhD Hôpital Pellegrin, Bordeaux
Study Director: Sandrine MEUNIER, MD Hôpital Edouard Heriot, Lyon
Study Director: Gwenaêlle ROUSSEY, MD Hôpital Hotel Dieu, Nantes
Study Director: Mohammed HAMIDOU, MD, PhD Hôpital Hotel Dieu, Nantes
Study Director: Bernard BONNOTTE, MD, PhD Hôpital du Bocage, Dijon
Study Director: Yves TANTER, MD Hôpital du Bocage, Dijon
Study Director: Jacques POURRAT, MD, PhD Hôpital de Rangueil, Toulouse
Study Director: Marie-Christine THOURET, MD CHU de l'Archet 2, Nice
Study Director: Philippe VANHILLE, MD CH de Valenciennes, Valenciennes
Study Director: Nicolas LIMAL, MD Hôpital Henri Mondor, Créteil
Study Director: Philippe REMY, MD Hôpital Henri Mondor, Créteil
Study Director: Jean-Michel KORACH, MD CHG Châlons-en-Champagne, Châlons-en-Champagne
Study Director: Carine GREIB, MD Hôpital Haut-Lévêque, Pesac
Study Director: Jean-Louis PALLOT, MD CHI André Grégoire, Montreuil
Study Director: Alain WYNCKEL, MD CHU de Reims, Reims
Study Director: Claire CAZALETS, MD Hôpital Sud, Rennes
Study Director: Bertrand DE CAGNY, MD CHU d'Amiens, Amiens
Study Director: Claire PRESNE, MD CHU D'Amiens, Amiens
Study Director: Cécile FOHRER, MD Hôpital de Haute-Pierre, Strasbourg
Study Director: Karin BILGER, MD Hôpital de Haute-Pierre, Strasbourg
Study Director: Bruno LIOURE, MD Hôpital de Haute-Pierre, Strasbourg
Study Director: Raoul HERBRECHT, MD, PhD Hôpital de Haute-Pierre, Strasbourg
Study Director: Dominique PLANTAZ, MD, PhD Hôpital Nord, Grenoble
Study Director: Hubert NIVET, MD, PhD Hôpital Gatien de Clovheville, Tours
Study Director: Emmanuel FLECK, MD Hôpital Saint Louis, La Rochelle
Study Director: Jean-Philippe COINDRE, PH Centre Hospitalier du Mans, LE MANS
Study Director: François MAURIER, PH Hôpital Sainte-Blandine Service de Médecine Interne, METZ
Study Director: Mario OJEDA-URIBE, PH Centre Hospitalier Régional de MULHOUSE Hôpital Edouard Muller, Département d'Hématologie, Unité de thérapie cellulaire et greffes, MULHOUSE
Study Director: Christophe RIDEL, PH Hôpital Tenon, Service de Néphrologie et de Transplantation rénale, PARIS
Study Director: François BRIVET, PH Hôpital Antoine Béclère, Service de réanimation médicale, CLAMART
Study Director: Sylvain LAVOUÉ, PH CHU Pontchaillou, Service de maladies infectieuses et réanimation médicale, RENNES
Study Director: Sébastien CANET, PH Centre Hospitalier de Perpignan, Hôpital Saint-Jean, Service de Néphrologie, Hémodialyse, PERPIGNAN
Study Director: François PROVOT, PH Centre Hospitalier Régional Universitaire de Lille, Hôpital Calmette, Pôle de Néphrologie, LILLE
Study Director: Claude GUYOT, PH CHU de Nantes, Hôpital de jour et d'Hémodialyse pédiatrique
Study Director: Xavier BELENFANT, PH CHI André Grégoire de Montreuil, Service de Néphrologie, Diabète et Dialyse, MONTREUIL
Study Director: Laurent PERARD, PH Hôpital Edouard Herriot, Service de Médecine Interne, LYON
Study Director: Edouard DEVAUD, PH CHR de Pontoise Hôpital René Dubos, Service de Médecine Interne- Néphrologie- Dialyse, PONTOISE
Study Director: Arnaud BUFFIN, PH CH CHAMBERY, Service de Pédiatrie, CHAMBERY
Study Director: Tarik KANOUNI, PH CHU Montpellier Hôpital Lapeyronie, Service d'Hématologie et Oncologie médicale, MONTPELLIER
Study Director: Nicolas GAMBIER, PH Hôpital Avicenne, Service de Médecine Interne, BOBIGNY
Study Director: Alain DEVIDAS, PH CH Sud-Francilien- Hôpital Gilles de Corbeil, Service d'Hématologie Clinique, CORBEIL-ESSONNES
Study Director: Laure FEDERICI, PH CH Colmar- Hôpital Pasteur, Service de Médecine Interne, COLMAR
Study Director: Michel FOULARD, PH CHRU de Lille- Hôpital Jeanne de Flandre, Service de Néphrologie pédiatrique, LILLE
Study Director: Serge BOLOGNA, PH Hôpital Brabois Adulte, Service d'Hématologie, VANDOEUVRE-LÈS-NANCYS
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00426686     History of Changes
Other Study ID Numbers: PO51064
Study First Received: January 24, 2007
Last Updated: December 11, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
thrombotic thrombocytopenic purpura
prognostic factors
ADAMTS13

Additional relevant MeSH terms:
Purpura
Purpura, Thrombocytopenic
Purpura, Thrombotic Thrombocytopenic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Thrombophilia

ClinicalTrials.gov processed this record on April 23, 2014