Thalidomide for the treatment of severe recurrent epistaxis in hereditary hemorrhagic telangiectasia: clinical trial on the efficacy of oral administration and “in vitro” study of a new drug formulation for a topical effect

Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a genetic disease that leads to multiregional vascular malformations. Severe recurrent nasal bleeding is the most common presentation, frequently leading to severe anemia. Although not life threatening, severe nosebleeds have a great impact on quality of life and they represent the most important impediment in daily activities. Multiple therapeutic approaches have been tried, but all approaches are largely palliative with variable and temporary results. Since vascular abnormalities are involved in the development of HHT, drugs blocking vessel formation may be effective in its treatment. Thalidomide has been shown to be a potent inhibitor of vessel formation in experimental models. The aims of our study are to evaluate the effectiveness of thalidomide in reducing nosebleeds and to identify the lowest effective dose of the drug in patients with HHT refractory to standard therapy; moreover, to evaluate the possibility to provide a nasal formulation of thalidomide for a localized effect to avoid systemic unwanted side effects. Since nasal delivery could represent an innovative use of thalidomide towards HHT nosebleeds, liquid and dry nasal forms will be formulated and the in vitro drug release through nasal mucosa in animal models will be studied.