We designed a phase II, open-label study to evaluate the efficacy, tolerability, safety, and pharmacokinetics of orally doxycycline (100 mg BID) and tauroursodeoxycholic acid (TUDCA) (250 mg three times/day) administered continuously for 12 months. Primary endpoint is response rate defined as nonprogression of the neuropathy and of the cardiomyopathy. Since July 2010, we enrolled 20 patients. Seventeen patients have hereditary ATTR, two patients have senile systemic amyloidosis, and one is a domino recipient. Seven patients completed 12-month treatment, 10 completed 6-month treatment, two discontinued because of poor tolerability, and one is lost at follow-up. No serious adverse events were registered. No clinical progression of cardiac involvement was observed. The neuropathy (Neuropathy Impairment Score in the Lower Limbs [NIS-LL] and Kumamoto score) remained substantially stable over 1 year. These preliminary data indicate that the combination of Doxy-TUDCA stabilizes the disease for at least 1 year in the majority of patients with an acceptable toxicity profile.

Trial registration: ClinicalTrials.gov identifier: NCT01171859.