Efficacy of Thalidomide in the Treatment of Hereditary Hemorrhagic Telangiectasia

• Status: Completed
• Trial end date: 2016-10-11
• Target enrollment: 0
• Participant gender: All

Summary

Hereditary hemorrhagic telangiectasia (HHT) (OMIM 187300 and 600376), also known as Rendu-Osler-Weber syndrome, is an autosomal dominant disease and has a prevalence between 1:5000 and 1:8000 in different populations. Clinically, the occurrence of mucocutaneous and gastrointestinal telangiectasias and of systemic arteriovenous malformations is commonly observed. Recurrent and severe epistaxis, due to the presence of telangiectasias in nasal mucosa, is the most common presentation of HHT, frequently leading to severe anemia requiring intravenous iron and blood transfusions. Although not life threatening, severe epistaxis has a great impact on quality of life in HHT patients and it represents the most important impediment in daily activities, that poses therapeutic challenge. Recently, angiogenesis has been implicated in the pathogenesis of HHT. Circulating concentrations of both TGF-beta and vascular endothelial growth factor (VEGF) are significantly elevated and therefore, anti-angiogenic substances may be effective in the treatment of vascular malformations in this disease. Thalidomide functions as a potent immunosuppressive and antiangiogenic agent. The aim of this study is to assess the clinical effects of thalidomide therapy on the severity of epistaxis in subjects with HHT who are refractory to standard therapies.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: IRCCS Policlinico S. Matteo
• Treatments: Thalidomide

Criteria

Inclusion Criteria:

• Diagnosis of HHT, according to the diagnostic criteria world-wide recognized (Curacao criteria), with severe recurrent epistaxis (grade 2-3 according to the criteria proposed by Pagella et al., i.e. at least one episode of overt bleeding/week requiring at least one blood transfusion during the last three months), and refractory to mini-invasive surgical procedures, i.e. argon plasma coagulation. For these patients, there is no effective treatment option currently available

• Age > 18 years

• Ability of signing written informed consent

• Women of childbearing potential:

• declared intention not to start a pregnancy throughout the study and for four weeks following the date of the last dose of thalidomide (safe contraception, see Celgene guidelines, "Programma di Prevenzione della Gravidanza")

• negative serum pregnancy test obtained within 48 hours prior to the first dose of Thalidomide

• declared intention to undergo pregnancy tests periodically while on the study medication

• Males with female partner of childbearing potential:

• declared intention not to father throughout the study and for one week following the date of the last dose of thalidomide (safe contraception, see Celgene guidelines, "Programma di Prevenzione della Gravidanza")

• Estimated life expectancy must be greater than 10 months

Exclusion Criteria:

• Pregnant or lactating women, or potentially fertile (both males and females) who have not agreed to avoid pregnancy during the trial period and for four weeks (females) or one week (males) following the date of the last dose of thalidomide

• Neurological diseases

• Psychiatric illness that would prevent granting of informed consent

• Active cardiovascular disease

• High risk for thromboembolic events (comorbidities, such as diabetes or uncontrolled infections, malignancy, immobility, prior history of thromboembolic events, use of erythropoietic agents or other agents such as hormone replacement therapy, central venous catheter, anti-cardiolipin, or anti-beta2 glycoprotein antibodies)

• Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption since thalidomide capsules contain lactose