Eltrombopag and the Bcl-xL Pathway in Idiopathic Thrombocytopenic Purpura (ITP)
Summary
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.
Description
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.
Study Design
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Idiopathic Thrombocytopenic Purpura
Intervention
Promacta (eltrombopag)
Location
Weill Cornell Medical College
New York
New York
United States
10065
Status
Recruiting
Source
Weill Medical College of Cornell University
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00902018
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Purpura, Thrombocytopenic
Any form of purpura in which the PLATELET COUNT is decreased. Many forms are thought to be caused by immunological mechanisms.
Purpura, Thrombocytopenic, Idiopathic
Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.
Immunoglobulins, Intravenous
Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.
Purpura, Schoenlein-henoch
A systemic non-thrombocytopenic purpura caused by HYPERSENSITIVITY VASCULITIS and deposition of IGA-containing IMMUNE COMPLEXES within the blood vessels throughout the body, including those in the kidney (KIDNEY GLOMERULUS). Clinical symptoms include URTICARIA; ERYTHEMA; ARTHRITIS; GASTROINTESTINAL HEMORRHAGE; and renal involvement. Most cases are seen in children after acute upper respiratory infections.
Purpura, Thrombotic Thrombocytopenic
An acquired, congenital, or familial disorder caused by PLATELET AGGREGATION with THROMBOSIS in terminal arterioles and capillaries. Clinical features include THROMBOCYTOPENIA; HEMOLYTIC ANEMIA; AZOTEMIA; FEVER; and thrombotic microangiopathy. The classical form also includes neurological symptoms and end-organ damage, such as RENAL FAILURE.
Clinical Trials
Clinical Evaluation of Eltrombopag in Chronic Idiopathic Thrombocytopenic Purpura (ITP)
An open-label, dose-adjustment extension study to evaluate the safety and efficacy of eltrombopag for treatment of subjects with ITP who have previously been enrolled in the eltrombopag tr...
EXTEND (Eltrombopag Extended Dosing Study)
An open-label, dose-adjustment, extension study to evaluate the safety and efficacy of eltrombopag for the treatment of subjects with idiopathic thrombocytopenic purpura (ITP) who have pre...
Since Idiopathic Trombocytopenic Purpura (ITP) affects women who are of reproductive capacity and taking into account the lack of data concerning Eltrombopag (Promacta) use during pregnanc...
Platelet Function in Idiopathic Thrombocytopenic Purpura (ITP) Patients With Eltrombopag
This is a single-center, prospective, controlled study with one eltrombopag treatment group and 2 control groups, one on standard steroid treatment, and another one untreated. The aim of...
Clinical Evaluation of SB-497115-GR in Chronic Idiopathic Thrombocytopenic Purpura (ITP)
This is a Phase II/III multicenter study comprising of the double-blind, followed by open-label phases to evaluate and compare the efficacy and tolerability of eltrombopag (SB-497115-GR) i...
PubMed Articles
The population pharmacokinetics of eltrombopag were characterized in healthy subjects (n = 111) and patients with idiopathic thrombocytopenic purpura (ITP) (n = 88) using nonlinear mixed-effects model...
Fifty-four adult German patients suffering from idiopathic thrombotic thrombocytopenic purpura (TTP) have been examined for HLA class II. All patients presented autoantibodies against ADAMTS13 and ADA...
Thrombelastography (TEG) analyses the status of blood coagulation including abnormalities associated with low platelet count. The aim of this study was to investigate the changes in TEG parameters in...
Pharmacological profile of AS1670542, a novel orally-active human thrombopoietin receptor agonist.
Eltrombopag, an orally-active small molecule thrombopoietin (TPO) receptor agonist, was used for the first time in 2008 to treat patients with chronic idiopathic thrombocytopenic purpura. Here, we inv...
Pathogenesis and treatment of acquired idiopathic thrombotic thrombocytopenic purpura.
