ADAMTS13 in Thrombotic Thrombocytopenic Purpura (ADAMTS13)

December 11, 2012 updated by: Assistance Publique - Hôpitaux de Paris

ADAMTS13-related Prognostic Factors in Adult and Pediatric Thrombotic Thrombocytopenic Purpura

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

153

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clamart, France, 92140
        • Hôpital Antoine Béclère

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: paul COPPO, MD, PhD, Hôpital Saint Antoire, PARIS
  • Study Director: Elie AZOULAY, MD, PhD, Hopital Saint Louis Paris
  • Study Director: Benoît SCHLEMMER, MD, Hopital Saint Louis Paris
  • Study Director: Eric OKSENHENDLER, MD, Hopital 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, Hopital Antoine Béclère, CLAMART
  • Study Director: Thierry LEBLANC, MD, Hopital 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, Hopital Henri Mondor, Creteil
  • Study Director: Philippe REMY, MD, Hopital Henri Mondor, Creteil
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

January 24, 2007

First Submitted That Met QC Criteria

January 24, 2007

First Posted (Estimate)

January 25, 2007

Study Record Updates

Last Update Posted (Estimate)

December 12, 2012

Last Update Submitted That Met QC Criteria

December 11, 2012

Last Verified

April 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PO51064

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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