Transthyretin Amyloidosis | Safety, Efficacy and Pharmacokinetics of Doxycycline Plus Tauroursodeoxycholic Acid in Transthyretin Amyloidosis

Transthyretin Amyloidosis research study

What is the primary objective of this study?

This study is being conducted to explore the potential benefits of a twelve-month doxycycline (at the best tolerated dose of 200 mg/day) and tauroursodeoxycholic acid (750 mg/day) treatment on disease progression in patients affected by transthyretin amyloidosis, including: 1) patients not eligible for liver transplantation; 2) patients eligible for liver transplantation, as a \"bridge\" therapy between the time of diagnosis and surgery, with the aim of stabilizing the disease; 3) patients showing disease progression after liver transplantation performed since at least 1 year. It is a phase II, therapeutic exploratory, two-part, 18-month, single centre, prospective study. Part I is a 12-month, open label treatment period in which doxycycline (200 mg/day, continuously) and tauroursodeoxycholic acid (750 mg/day continuously) are administered to 40 consenting subjects with transthyretin amyloidosis. Part II is a withdrawal period in which subjects will be monitored for disease progression. During part I, subjects will be evaluated at baseline (study Day 0), and then after 3, 6, 9 and 12 months of doxycycline plus tauroursodeoxycholic acid treatment or at premature treatment discontinuation; during part II, they will be assessed at months 15 and 18. Monthly phone contacts and blood tests will be performed to monitor potential adverse events.

Who is eligible to participate?

Inclusion Criteria: - Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens; - Molecular definition of the transthyretin (TTR) mutation or immunohistochemical staining of amyloid fibrils with anti-TTR antibody; - ECOG performance status (PS) 0, 1, 2; - New York Heart Association (NYHA) class ≤III - Systolic blood pressure ≥100 mmHg (standing) - Must have symptomatic organ involvement with amyloid to justify therapy; must have evidence of neuropathy and/or cardiomyopathy progression after liver transplantation performed since at least one year. - Contraception for women of childbearing potential. Medically approved contraception could include abstinence. A negative serum pregnancy test is required prior to initiation of treatment with study medication. Exclusion Criteria: - Liver transplantation in the previous 12 months or liver transplantation anticipated in less than 6 months; - ALT and/or AST ≥ 2 x Upper Normal Limit (UNL); - Alkaline phosphatase ≥ 2 x UNL; - Creatinine clearance < 30 ml/min; - Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study; - Echocardiographic ejection fraction < 50%; - Other neuropathies, due to vitamin B12 deficiency, alcoholism, hypothyroidism, uremia, diabetes mellitus, vasculitides; - History of poor compliance; - History of hypersensitivity to any of the ingredients of the study therapies; - Use of any investigational drug, device (or biologic) within 4 weeks prior to study entry or during the study.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Transthyretin Amyloidosis

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Doxycycline + Tauroursodeoxycholic aciddoxycycline 100 mg twice a day for 12 months; tauroursodeoxycholic acid 250 mg three times a day for 12 months

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Doxycycline + Tauroursodeoxycholic acid

Study Status


Start Date: July 2010

Completed Date: October 2015

Phase: Phase 2

Type: Interventional


Primary Outcome: Response rate to doxycycline + tauroursodeoxycholic acid treatment

Secondary Outcome: Number of patients experiencing treatment-emergent adverse events

Study sponsors, principal investigator, and references

Principal Investigator: Giampaolo Merlini, MD

Lead Sponsor: IRCCS Policlinico S. Matteo


More information:

Cardoso I, Saraiva MJ. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J. 2006 Feb;20(2):234-9.

Discuss Doxycycline