NCT02016365

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
55

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Feb 2012

Typical duration for phase_2

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2012

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

April 19, 2012

Completed
1.7 years until next milestone

First Posted

Study publicly available on registry

December 20, 2013

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2014

Completed
Last Updated

May 12, 2016

Status Verified

May 1, 2016

Enrollment Period

2.8 years

First QC Date

April 19, 2012

Last Update Submit

May 11, 2016

Conditions

Transthyretin AmyloidosisCardiomyopathy

Keywords

Transthyretin amyloidosisCardiomyopathyATTRneuropathy

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (5)

  • Modified Body Mass Index (mBMI) reduction

    12 month

  • Increase of septum thickness

    12 month

  • Neurologic Kumamoto Scale

    6, 12 and 18 month

  • Number of patients with adverse events

    During 12 month treatment and during 6 month follow-up

  • Blood work for potential drug-related adverse events

    18 months

Study Arms (1)

Doxycycline and UDCA

EXPERIMENTAL

Doxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously)

Drug: DoxycyclineDrug: Ursodeoxycholic acid

Interventions

DoxycyclineDRUG

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

Also known as: Doxyferm
Doxycycline and UDCA
Ursodeoxycholic acidDRUG

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

Also known as: Ursofalk
Doxycycline and UDCA

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Dept of Clinical Medicin, Ptieå Hospital

Piteå, SE-941 28, Sweden

Location

Dept of clinical medicin, Skellefteå Hospital

Skellefteå, SE-931 86, Sweden

Location

Dept of Clinical Medicine, Umeå University Hospital

Umeå, SE-90185, Sweden

Location

MeSH Terms

Conditions

Amyloidosis, Hereditary, Transthyretin-RelatedCardiomyopathies

Interventions

DoxycyclineUrsodeoxycholic Acid

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

TetracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsDeoxycholic AcidCholic AcidsBile Acids and SaltsSteroidsFused-Ring CompoundsCholanes

Study Officials

  • Ole B Suhr, MD PhD Prof

    Dept of Clinical Medicine and public Health, Umeå University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, MD, PhD

Study Record Dates

First Submitted

April 19, 2012

First Posted

December 20, 2013

Study Start

February 1, 2012

Primary Completion

December 1, 2014

Study Completion

December 1, 2014

Last Updated

May 12, 2016

Record last verified: 2016-05

Locations

SE(3)