Safety, Efficacy and Pharmacokinetics of Doxycycline Plus Tauroursodeoxycholic Acid in Transthyretin Amyloidosis
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|ClinicalTrials.gov Identifier: NCT01171859|
Recruitment Status : Completed
First Posted : July 29, 2010
Last Update Posted : February 25, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Transthyretin Amyloidosis||Drug: Doxycycline + Tauroursodeoxycholic acid||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Single Center, Twelve-month, Open-label, Prospective Study Followed by a Six-month Withdrawal Period to Evaluate the Efficacy, Tolerability, Safety and Pharmacokinetics of Doxycycline in Combination With Tauroursodeoxycholic Acid in Transthyretin Amyloidosis|
|Study Start Date :||July 2010|
|Actual Primary Completion Date :||April 2015|
|Actual Study Completion Date :||October 2015|
|Experimental: Doxycycline + Tauroursodeoxycholic acid||
Drug: Doxycycline + Tauroursodeoxycholic acid
doxycycline 100 mg twice a day for 12 months; tauroursodeoxycholic acid 250 mg three times a day for 12 months
- Response rate to doxycycline + tauroursodeoxycholic acid treatment [ Time Frame: One year ]
A responder is a subject with:
- a modified body mass index (mBMI) reduction of less than 10% and a change in the Neurologic Impairment Score-Lower Limbs (NIS-LL) <2 (in subjects with peripheral neuropathy);
- a modified body mass index (mBMI) reduction of less than 10% and an increase in N-terminal natriuretic peptide type B (NT-proBNP) concentration of less than 30% or < 300 pg/mL (in subjects with isolated cardiomyopathy).
- Number of patients experiencing treatment-emergent adverse events [ Time Frame: One year ]
- Change in quality of life [ Time Frame: Every six months ]SF-36 scale
- doxycycline pharmacokinetics (PK) [ Time Frame: Every three months ]
- response in autonomic dysfunction, sensory-motor peripheral neuropathy and visceral organ involvement [ Time Frame: One year ]response assessed according to the Kumamoto Scale score
- neurologic response [ Time Frame: One year ]response assessed by motor and sensory nerves conduction studies
- Incidence of patients discontinuing from the study because of clinical or laboratory adverse events [ Time Frame: One year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01171859
|Amyloid Research and Treatment Centre, Biotechnology Research Laboratories|
|Pavia, Italy, 27100|
|Principal Investigator:||Giampaolo Merlini, MD||IRCCS Policlinico San Matteo|