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

Cardiomyopathy Clinical Trial

— Dox/Urso  

Official title:

A Phase II Multicenter Pilot Study of the Safety and Efficacy of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02016365
• Other study ID #: EudraCT No:2011-005236-25
• Status: Completed
• Phase: Phase 2
• First received: April 19, 2012
• Last updated: May 11, 2016
• Start date: February 2012
• Est. completion date: December 2014

Study information

• Verified date: May 2016
• Source: Umeå University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyloid Neuropathies, Familial
• Amyloidosis
• Cardiomyopathies
• Cardiomyopathy
• Disease Progression
• Transthyretin Amyloidosis

Intervention

Drug:
• Doxycycline
200 mg/day (100 mg twice daily, orally) for 4 weeks with a pause of 2 weeks in combination with UDCA
• Ursodeoxycholic acid
750 mg/day (500 mg +250mg orally) continuously

Locations

Country	Name	City	State
Sweden	Dept of Clinical Medicin, Ptieå Hospital	Piteå
Sweden	Dept of clinical medicin, Skellefteå Hospital	Skellefteå
Sweden	Dept of Clinical Medicine, Umeå University Hospital	Umeå

Sponsors (1)

Lead Sponsor	Collaborator
Umeå University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	At 12 month treatment	No
Secondary	Modified Body Mass Index (mBMI) reduction	mBMI-reduction of less than 10%	12 month	No
Secondary	Increase of septum thickness	Increase of septum thickness = 2 mm	12 month	No
Secondary	Neurologic Kumamoto Scale	To assess the change from baseline in the neurologic Kumamoto Scale	6, 12 and 18 month	No
Secondary	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.	During 12 month treatment and during 6 month follow-up	Yes
Secondary	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.	18 months	Yes