Transthyretin AmyloidosisPhase 2Dox/UrsoNCT02016365
Safety and Efficacy Study of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
A Phase 2 study testing Doxycycline and Ursodeoxycholic acid in people with Transthyretin Amyloidosis and Cardiomyopathy, run by Umeå University at 3 sites in Sweden.
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Transthyretin Amyloidosis, Cardiomyopathy
- What is being tested?
- Doxycycline and Ursodeoxycholic acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 3 sitesSweden
- Study dates
- Feb 2012to Dec 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- New York Heart Association (NYHA) class <III
- Systolic blood pressure >100 mmHg (standing)
- Must have symptomatic organ involvement with amyloid to justify therapy
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
Sweden3 sites
Dept of Clinical Medicin, Ptieå Hospital
Piteå, SE-941 28
Dept of clinical medicin, Skellefteå Hospital
Skellefteå, SE-931 86
Dept of Clinical Medicine, Umeå University Hospital
Umeå, SE-90185
About this study
Official title: A Phase II Multicenter Pilot Study of the Safety and Efficacy of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
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.
- Conditions
- Transthyretin Amyloidosis, Cardiomyopathy
- Being tested
- Doxycycline, Ursodeoxycholic acid
- Keywords
- Transthyretin amyloidosis, Cardiomyopathy, ATTR, neuropathy
- Medical subject headings
- Amyloidosis, Hereditary, Transthyretin-Related, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Also called Doxyferm
200 mg/day (100 mg twice daily, orally) for 4 weeks with a pause of 2 weeks in combination with UDCA
Ursodeoxycholic acidDrug
Also called Ursofalk
750 mg/day (500 mg +250mg orally) continuously
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline and UDCA | Experimental | Doxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously) Receives: Drug: Doxycycline; Drug: Ursodeoxycholic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At 12 month treatment
Secondary outcomes (5)
Modified Body Mass Index (mBMI) reduction
mBMI-reduction of less than 10%
Measured: 12 month
Increase of septum thickness
Increase of septum thickness ≤ 2 mm
Measured: 12 month
Neurologic Kumamoto Scale
To assess the change from baseline in the neurologic Kumamoto Scale
Measured: 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.
Measured: 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.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2013 (estimated)
- Study startFeb 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin AmyloidosisStudies of the same condition, open and under way.
- More trials run by Umeå UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Umeå University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ole B Suhr, Professor, MD, PhD, Umeå University
- Investigators
- Ole B Suhr, MD PhD Prof, Principal investigator, Dept of Clinical Medicine and public Health, Umeå University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02016365
- Sponsor's protocol ID
- EudraCT No:2011-005236-25
- Acronym
- Dox/Urso
- Status last verified
- May 2016
- First submitted
- 19 Apr 2012
- Last updated
- 12 May 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multicenter Pilot Study of the Safety and Efficacy of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis
- ClinicalTrials.gov ID
- NCT02016365
- Acronym / sponsor ID
- Dox/Urso / EudraCT No:2011-005236-25
- Conditions
- Transthyretin Amyloidosis, Cardiomyopathy
- Keywords
- Transthyretin amyloidosis, Cardiomyopathy, ATTR, neuropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Umeå UniversityUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 20 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doxycycline and UDCA | Experimental | Drug: Doxycycline, Drug: Ursodeoxycholic acidDoxycycline (200 mg/day intermittently) and UDCA (750 mg/day continuously) |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoxycyclineAlso: Doxyferm200 mg/day (100 mg twice daily, orally) for 4 weeks with a pause of 2 weeks in combination with UDCA | Drug | Doxycycline and UDCA |
| Ursodeoxycholic acidAlso: Ursofalk750 mg/day (500 mg +250mg orally) continuously | Drug | Doxycycline and UDCA |
Primary outcome
The efficacy on serum N terminal proBNP (NT-proBNP)
Time frame: 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
5 secondary outcomes
Modified Body Mass Index (mBMI) reduction
Time frame: 12 month
Increase of septum thickness
Time frame: 12 month
Neurologic Kumamoto Scale
Time frame: 6, 12 and 18 month
Number of patients with adverse events
Time frame: During 12 month treatment and during 6 month follow-up
Blood work for potential drug-related adverse events
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ole B Suhr, MD PhD Prof principal investigator
Dept of Clinical Medicine and public Health, Umeå University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Doxycycline and Ursodeoxycholic acid in people with Transthyretin Amyloidosis and Cardiomyopathy, run by Umeå University at 3 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The efficacy on serum N terminal proBNP (NT-proBNP) (time frame: At 12 month treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2016.