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

Phase 2

Completed

• Conditions: Transthyretin Amyloidosis; Cardiomyopathy
• Interventions: Drug: Doxycycline; Drug: Ursodeoxycholic acid

• Registration Number: NCT02016365
• Lead Sponsor: Umeå University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-04-19
• Study First Submitted QC: 2013-12-13
• Study First Posted: 2013-12-20
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-11
• Last Update Posted: 2016-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 55

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Doxycycline and UDCA	Doxycycline	Doxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously)
Doxycycline and UDCA	Ursodeoxycholic acid	Doxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously)

Primary Outcome Measures

Name	Time	Method
The efficacy on serum N terminal proBNP (NT-proBNP)	At 12 month treatment	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

Secondary Outcome Measures

Name	Time	Method
Modified Body Mass Index (mBMI) reduction	12 month	mBMI-reduction of less than 10%
Increase of septum thickness	12 month	Increase of septum thickness ≤ 2 mm
Neurologic Kumamoto Scale	6, 12 and 18 month	To assess the change from baseline in the neurologic Kumamoto Scale
Number of patients with adverse events	During 12 month treatment and during 6 month follow-up	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.
Blood work for potential drug-related adverse events	18 months	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.

Trial Locations

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