Clinical trial NCT02016365: Safety and Efficacy Study of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
Official title: A Phase II Multicenter Pilot Study of the Safety and Efficacy of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transthyretin Amyloidosis
Cardiomyopathy
Keywords: Transthyretin amyloidosis
Cardiomyopathy
ATTR
neuropathy
Lead sponsor: Umeå University
Sponsor class: OTHER
First posted: 2013-12-20
Enrollment: 55
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective for this study is to evaluate the efficacy of doxycycline + ursodeoxycholic acid (UDCA) on disease progression in Transthyretin Amyloidosis (ATTR) subjects with cardiomyopathy with or without neuropathy.


Eligibility criteria: Inclusion Criteria:

* Cardiomyopathy with septal thickness \> 15 mm and/or S-NT-ProBNP \> 300 ng/
* Age \>50 years
* Male and females after menopause. Menopause is defined as 6 to 12 months of amenorrhea in a woman over 45 years of age.
* Written informed consent to be obtained prior to any study procedure
* 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.
* Molecular definition of the TTR mutation or immunohistochemical staining of amyloid fibrils with anti TTR antibody
* New York Heart Association (NYHA) class \<III
* Systolic blood pressure \>100 mmHg (standing)
* Must have symptomatic organ involvement with amyloid to justify therapy

Exclusion Criteria:

* Liver transplantation in the previous 6 months or liver transplantation anticipated in less than 6 months;
* ALT and/or AST \> 2 x upper normal limit (UNL);
* Creatinine clearance \< 30 ml/min (Cockcroft -Gault Formula)
* 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;
* 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.

Primary outcomes:
measure: The efficacy on serum N terminal proBNP (NT-proBNP)
timeFrame: At 12 month treatment
Secondary outcomes:
measure: Modified Body Mass Index (mBMI) reduction
timeFrame: 12 month
measure: Increase of septum thickness
timeFrame: 12 month
measure: Neurologic Kumamoto Scale
timeFrame: 6, 12 and 18 month
measure: Number of patients with adverse events
timeFrame: During 12 month treatment and during 6 month follow-up
measure: Blood work for potential drug-related adverse events
timeFrame: 18 months
Other outcomes:
Locations:
city: Piteå
country: Sweden
facility: Dept of Clinical Medicin, Ptieå Hospital
city: Skellefteå
country: Sweden
facility: Dept of clinical medicin, Skellefteå Hospital
city: Umeå
country: Sweden
facility: Dept of Clinical Medicine, Umeå University Hospital
Study officials:
affiliation: Dept of Clinical Medicine and public Health, Umeå University
name: Ole B Suhr, MD PhD Prof
role: PRINCIPAL_INVESTIGATOR
References: