Clinical Trial: Safety, Efficacy and Pharmacokinetics of Doxycycline Plus Tauroursodeoxycholic Acid in Transthyretin Amyloidosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary:

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.


Detailed Summary:
Sponsor: IRCCS Policlinico S. Matteo

Current Primary Outcome: 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).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • tolerability and safety of doxycycline + tauroursodeoxycholic acid treatment [ 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


Information By: IRCCS Policlinico S. Matteo

Dates:
Date Received: July 27, 2010
Date Started: July 2010
Date Completion:
Last Updated: February 24, 2016
Last Verified: February 2016