Conditions: Immune Thrombocytopenia
Keywords: ITP
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 20
Healthy volunteers: yes

Brief summary:
The purpose of this study is to further evaluate the effects that eltrombopag (and romiplostim) have 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 (now Novartis) 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 and romiplostim affect subjects and their platelets to determine how the study drug should best be used in ITP treatment.

Detailed description:
The B-cell lymphoma extra large (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 Thrombopoietin (TPO) mediated activation of Akt pathways mediated by Jak2 and Stat 5 (possibly by Stat 3 as well). (e.g., Kozuma et. al., Journal of Thrombosis and Haemostasis). 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 thrombopoietin-receptor (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.

Arms:
arm 1: 10 ITP patients were treated with daily oral eltrombopag 75mg for 2 weeks and complete testing was done at weekly intervals 3 times they then were allowed to receive long-term eltrombopag arm 2: 3 of the patients who received eltrombopag were also treated with romiplostim 10 micrograms/kg weekly for 2 weeks with the same complete testing done at weekly intervals three times after a washout period \> 1 month they then resumed long-term eltrombopag arm 3: no intervention single blood draw with complete studies

Interventions: intervention 1: Eltrombopag intervention 2: Romiplostim intervention 3: healthy controls
Intervention descriptions: intervention 1: The 10 subjects will be treated with eltrombopag 75 mg once daily. Patients will be monitored 3 times, weekly, for the first 2 weeks, and then monitored as clinically indicated as they continue eltrombopag dosing for 3-4 months. intervention 2: three of the patients treated with eltrombopag will be treated with weekly romiplostim at a dose of 10 micrograms/kg weekly for 2 weeks with testing at weekly intervals for 3 times intervention 3: single blood draw for all measures included in the intervention arms

Protocol document: