A phase II multicenter pilot study of the safety and efficacy of Doxycycline/UrsoDeoxyCholicAcid on disease progression in ATTR amyloidosis
- Conditions
- Transthyretin amyloidosisMedDRA version: 14.1Level: LLTClassification code 10019893Term: Hereditary neuropathic amyloidosis, Swedish typeSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2011-005236-25-SE
- Lead Sponsor
- meå University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
1)Cardiomyopahty with septal thickness >/= 15 mm and/or S-NT-ProBNP >/=300 ng/L
2)Age >/=50 years
3)Male and females after menopause
4)Written informed consent to be obtained prior to any study procedure
5)Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, and typing of amyloid deposits as TTR and identification of amyloid fibril type.
6)Molecular definition of the TTR mutation or immunohistochemical staining of amyloid fibrils with anti TTR antibody
7)NYHA class 8)Systolic blood pressure >/=100 mmHg (standing)
9)Must have symptomatic organ involvement with amyloid to justify therapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
Liver transplantation in the previous 6 months or liver transplantation anticipated in less than 6 months;
2) ALT and/or AST >/= 2 x UNL;
3) Creatinine clearance < 30 ml/min (Cocroft-Gault Formula)
4) Any other lab values, illness or condition that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study;
5) History of hypersensitivity to any of the ingredients of the study therapies;
6) Use of any investigational drug, device (or biologic) within 4 weeks prior to study entry or during the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of doxycycline + UDCA on disease progression in ATTR subjects with cardiomyopathy with or without neuropathy.;Secondary Objective: 1. To evaluate the safety and tolerability of doxycyclin + UDCA in ATTR subjects over 12 months.<br>2. To evaluate symptoms and signs of peripheral sensorimotor neuropathy when present (Kumamoto Scale).<br>3. To evaluate disease evolution (maintenance of response, occurrence of disease progression) over 18 months.<br>4. To evaluate the outcome of the treatment with regard to type of amyloid fibrills<br>;Primary end point(s): Response rate to doxycycline + UDCA treatment at month 12. A responder is an ATTR subject with:<br><br>- a reduction of, or an increase in serum NT-proBNP concentration of less than 30% of pre-treatment level will be regarded as consistent with treatment efficacy.<br>;Timepoint(s) of evaluation of this end point: After 12 month of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): -mBMI-reduction of less than 10% after 12 months of treatment<br>- increase of septum thickness = 2 mm during 12 months of treatment.<br>- to assess the change from baseline in the neurologic Kumamoto Scale at months 6, 12 and 18; <br>- to assess the tolerability and safety of the treatment, i.e. monitoring and recording all adverse events (AEs) and serious adverse events (SAEs), and the regularly scheduled monitoring of hematology, blood chemistry, physical examinations, and blood pressure over 12 months and 18 months.<br>;Timepoint(s) of evaluation of this end point: At 6, 12 and 18 month