Safety and Efficacy Study of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis

Phase 2CompletedNCT02016365

Umeå University55 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Transthyretin Amyloidosis Cardiomyopathy

Interventions

DoxycyclineDRUG

200 mg/day (100 mg twice daily, orally) for 4 weeks with a pause of 2 weeks in combination with UDCA

Ursodeoxycholic acidDRUG

750 mg/day (500 mg +250mg orally) continuously

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

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.

Locations (3)

Dept of Clinical Medicin, Ptieå Hospital

Piteå, Sweden

Dept of clinical medicin, Skellefteå Hospital

Skellefteå, Sweden

Dept of Clinical Medicine, Umeå University Hospital

Umeå, Sweden

Outcomes

Primary Outcomes

The efficacy on serum N terminal proBNP (NT-proBNP)

The primary endpoint of the study is the response rate to doxycycline + UDCA treatment at month 12. A responder is an ATTR subject with: \- 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

Time frame: At 12 month treatment

Secondary Outcomes

Modified Body Mass Index (mBMI) reduction

mBMI-reduction of less than 10%

Time frame: 12 month

Increase of septum thickness

Increase of septum thickness ≤ 2 mm

Time frame: 12 month

Neurologic Kumamoto Scale

To assess the change from baseline in the neurologic Kumamoto Scale

Time frame: 6, 12 and 18 month

Number of patients with adverse events

To assess the tolerability and safety of the treatment, the number of patients with adverse reactions will be recorded. Monthly phone contacts will be performed for monitoring of the treatment safety. The safety profile of doxycycline + UDCA will be assessed through the recording, reporting and analysis of baseline medical conditions, physical examination findings including vital signs and laboratory tests. These will be compared to analysis results observed during the study.

Time frame: During 12 month treatment and during 6 month follow-up

Blood work for potential drug-related adverse events

To assess the tolerability and safety of the treatment, blood work \[e.g.complete blood count, creatinine and aspartate transaminase (AST), alkaline phosphatase(ALT)\] for potential drug-related adverse events will be drawn at 1, 3, 6, 9, 12 and 18 month. The safety profile of doxycycline + UDCA will be assessed through the recording, reporting and analysis of baseline medical conditions, physical examination findings including vital signs and laboratory tests. These will be compared to analysis results observed during the study.

Data from ClinicalTrials.gov

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