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Trial record 9 of 368 for:    transthyretin

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
Sponsor:
Information provided by (Responsible Party):
Giampaolo Merlini, IRCCS Policlinico S. Matteo

Tracking Information
First Submitted Date  ICMJE July 27, 2010
First Posted Date  ICMJE July 29, 2010
Last Update Posted Date February 25, 2016
Study Start Date  ICMJE July 2010
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2010)
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 Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01171859 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2011)
  • 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 Measures  ICMJE
 (submitted: July 28, 2010)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Efficacy and Pharmacokinetics of Doxycycline Plus Tauroursodeoxycholic Acid in Transthyretin Amyloidosis
Official Title  ICMJE 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
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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Transthyretin Amyloidosis
Intervention  ICMJE Drug: Doxycycline + Tauroursodeoxycholic acid
doxycycline 100 mg twice a day for 12 months; tauroursodeoxycholic acid 250 mg three times a day for 12 months
Study Arms  ICMJE Experimental: Doxycycline + Tauroursodeoxycholic acid
Intervention: Drug: Doxycycline + Tauroursodeoxycholic acid
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 28, 2010)
40
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE October 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01171859
Other Study ID Numbers  ICMJE DOXYTUDCA2010
2010-020422-17 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Giampaolo Merlini, IRCCS Policlinico S. Matteo
Study Sponsor  ICMJE IRCCS Policlinico S. Matteo
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Giampaolo Merlini, MD IRCCS Policlinico San Matteo
PRS Account IRCCS Policlinico S. Matteo
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP