Eltrombopag and the Bcl-xL Pathway in Idiopathic Thrombocytopenic Purpura (ITP)
The purpose of this study is to further evaluate the effects that eltrombopag has on platelets in subjects with chronic ITP. Eltrombopag is approved by the Food and Drug Administration (FDA) for the treatment of low platelets in patients with chronic ITP. It is being further studied by GlaxoSmithKline in other conditions associated with low platelets. This research study is being done because eltrombopag has been shown to increase platelet counts in a different way than other therapies for ITP. The investigators want to further study how eltrombopag affects subjects and their platelets to determine how the study drug should best be used in ITP treatment.
Idiopathic Thrombocytopenic Purpura
Drug: Promacta (eltrombopag)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Effect of Eltrombopag on Platelet Survival: the Role of the BcL-xL Pathway|
- To determine how eltrombopag affects platelet counts. [ Time Frame: 2-4 weeks. ] [ Designated as safety issue: No ]
- To determine effect of eltrombopag on platelet apoptosis. [ Time Frame: First two weeks of study. ] [ Designated as safety issue: Yes ]
- To determine how eltrombopag affects platelet function and platelet survival. [ Time Frame: First two weeks of study. ] [ Designated as safety issue: Yes ]
- To continue to assess the safety and efficacy of eltrombopag. [ Time Frame: First two weeks of study. ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2009|
|Estimated Study Completion Date:||January 2014|
|Estimated Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Drug: Promacta (eltrombopag)
Subjects will be treated with eltrombopag 75 mg once daily. Patients will be monitored 3 times a week for the first 2 weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for 3-4 months.
The Bcl-xL/Bak balance has been identified as an intrinsic mechanism that is critical in determining platelet lifespan (Mason, Cell 2007). There is evidence that Bcl-xL protein expression in megakaryocytes is regulated by TPO-mediated activation of Akt pathways mediated by Jak2 and Stat 5 (possibly by Stat 3 as well). (e.g. Kozuma et al, J Thromb Haemost 2007). Little is known about the Bcl-xL / Bak axis in patients with ITP, or the effect of TPO-R stimulation on platelet survival in patients with ITP. The TPO effect may be a result of stimulation of TPO-R signalling in megakaryocytes altering the packaging of Bcl-xl into platelets, or be a direct effect of platelet TPO-R stimulation as described above.
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|Principal Investigator:||James B Bussel, MD||Weill Medical College of Cornell University|