Efficacy of thalidomide in the treatment of heavy and frequent nose bleeding in patients affected by hereditary hemorrhagic telangiectasia

Phase 1

Conditions: Severe recurrent epistaxis in hereditary hemorrhagic telangiectasia
MedDRA version: 14.1Level: LLTClassification code 10038554Term: Rendu-Osler-Weber syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]

Registration Number: EUCTR2011-004096-36-IT

Lead Sponsor: OSPEDALE POLICLINICO S. MATTEO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 31

Inclusion Criteria

- Diagnosis of HHT, according to the diagnostic criteria world-wide recognized (Curacao criteria, with severe recurrent epistaxis (grade 2-3) and refractory to mini-invasive surgical procedures. - 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, 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 - Estimated life expectancy must be greater than 10 months
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 11
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the clinical effects of thalidomide therapy on the severity of epistaxis in subjects with HHT who are refractory to standard therapies.;Secondary Objective: - Safety and Tolerability - To ascertain whether thalidomide reduces telangiectasias in nasal mucosa - To assess specific biological and clinical parameters predictable for patients response and side effects profile.;Primary end point(s): Percentage of patients showing a decrease in the frequency, intensity and duration of epistaxis and in the blood transfusion requirement.;Timepoint(s) of evaluation of this end point: Not applicable

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Size and number of telangiectasias evaluated by endoscopy of nasal mucosa at baseline and at least every 8 weeks thereafter - Requirement of blood transfusions - Minimum dose of the drug that reduces bleeding - Time to Response - Time to relapse after the end of treatment - Safety and tolerability of thalidomide in HHT - Correlations between the mutations that are responsible for HHT and response to treatment - Correlations between polymorphisms of CYP2C19 and response to treatment - Correlations between polymorphisms of CYP2C19 and side effects profile;Timepoint(s) of evaluation of this end point: Not applicable