Safety and Efficacy Study of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis (Dox/Urso)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Umeå University
Sponsor:
Information provided by (Responsible Party):
Ole B Suhr, Professor, MD, PhD, Umeå University
ClinicalTrials.gov Identifier:
NCT02016365
First received: April 19, 2012
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Transthyretin Amyloidosis
Cardiomyopathy
Drug: Doxycycline
Drug: Ursodeoxycholic acid
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Multicenter Pilot Study of the Safety and Efficacy of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis

Resource links provided by NLM:


Further study details as provided by Umeå University:

Primary Outcome Measures:
  • The efficacy on serum N terminal proBNP (NT-proBNP) [ Time Frame: At 12 month treatment ] [ Designated as safety issue: No ]

    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:
  • Modified Body Mass Index (mBMI) reduction [ Time Frame: 12 month ] [ Designated as safety issue: No ]
    mBMI-reduction of less than 10%

  • Increase of septum thickness [ Time Frame: 12 month ] [ Designated as safety issue: No ]
    Increase of septum thickness ≤ 2 mm

  • Neurologic Kumamoto Scale [ Time Frame: 6, 12 and 18 month ] [ Designated as safety issue: No ]
    To assess the change from baseline in the neurologic Kumamoto Scale

  • Number of patients with adverse events [ Time Frame: During 12 month treatment and during 6 month follow-up ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 30
Study Start Date: February 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxycycline and UDCA
Doxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously)
Drug: Doxycycline
200 mg/day (100 mg twice daily, orally) for 4 weeks with a pause of 2 weeks in combination with UDCA
Other Name: Doxyferm
Drug: Ursodeoxycholic acid
750 mg/day (500 mg +250mg orally) continuously
Other Name: Ursofalk

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02016365

Contacts
Contact: Ole B Suhr, MD PhD Prof +46 732-670 762 ole.suhr@medicin.umu.se

Locations
Sweden
Dept of Clinical Medicin, Ptieå Hospital Recruiting
Piteå, Sweden, SE-941 28
Contact: Katarzyna Liszewska, MD    0911 - 750 00 ext 232    Katarzyna.Liszewska@nll.se   
Principal Investigator: Katarzyna Liszewska, MD         
Dept of clinical medicin, Skellefteå Hospital Recruiting
Skellefteå, Sweden, SE-931 86
Contact: Lars Wikström, MD    +46 910-7710 00 ext 1667    lars.wikstrom@vll.se   
Principal Investigator: Lars Wikström, MD         
Dept of Clinical Medicine, Umeå University Hospital Recruiting
Umeå, Sweden, SE-90185
Contact: Marja-Liisa Lammi Tavelin, MSc    +46 90 785 8039    marjaliisa.lammitavelin@vll.se   
Principal Investigator: Ole B Suhr, MD PhD Prof         
Sponsors and Collaborators
Umeå University
Investigators
Principal Investigator: Ole B Suhr, MD PhD Prof Dept of Clinical Medicine and public Health, Umeå University
  More Information

No publications provided

Responsible Party: Ole B Suhr, Professor, MD, PhD, Professor, MD, PhD, Umeå University
ClinicalTrials.gov Identifier: NCT02016365     History of Changes
Other Study ID Numbers: EudraCT No:2011-005236-25
Study First Received: April 19, 2012
Last Updated: December 13, 2013
Health Authority: Sweden: Medical Products Agency

Keywords provided by Umeå University:
Transthyretin amyloidosis
Cardiomyopathy
ATTR
neuropathy

Additional relevant MeSH terms:
Amyloidosis
Amyloidosis, Familial
Disease Progression
Amyloid Neuropathies, Familial
Cardiomyopathies
Proteostasis Deficiencies
Metabolic Diseases
Disease Attributes
Pathologic Processes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Amyloid Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn
Metabolism, Inborn Errors
Heart Diseases
Cardiovascular Diseases
Doxycycline
Ursodeoxycholic Acid
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Cholagogues and Choleretics
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 21, 2014