AmyloidosisPhase 2NCT01677286

Safety and Effect of Doxycycline in Patients With Amyloidosis

A Phase 2 study testing Doxycycline 100 mg po bid x 12 months in people with Amyloidosis, run by Boston University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The tetracycline antibiotic doxycycline disrupts A beta amyloid fibrils (AB) in Alzheimer's disease, transthyretin (ATTR) amyloid fibrils in familial amyloidotic polyneuropathy, and immunoglobulin light chain (AL) amyloid fibrils in transgenic mouse models of disease. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Amyloidosis
What is being tested?: Doxycycline 100 mg po bid x 12 months
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 1 siteUnited States
Study dates: Jul 2012to 15 Dec 2015
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18 or older
Biopsy-proven amyloidosis
Biochemical or clinical evidence of amyloid induced end-organ dysfunction

Who cannot join

Concurrent use of other tetracyclines
Ongoing active treatment for amyloidosis
Pregnancy or unwillingness to use contraception by women of childbearing age
Doxycycline drug allergy/hypersensitivity
ECOG performance status > 3
NYHA class > 3

Show all 9Show fewer

Renal insufficiency (estimated creatinine clearance < 25 ml/min)
Transaminitis (AST or ALT > 5 times upper limit of normal)
Diabetes mellitus or hemoglobin A1C > 6.2%

Trial locations and contacts

1 site in 1 country.

United States1 site

Boston University
Boston, Massachusetts, 02118

Other trials in United States

About this study

Official title: A Phase II Study of Doxycycline in Patients With Amyloidosis

This single-center, twelve-month, open-label, prospective, pilot phase II study aims to determine whether doxycycline reduces amyloid deposits and improves organ function in patients with systemic or localized amyloidosis.

The investigators plan to enroll patients with measurable amyloid disease according to internationally-accepted diagnostic criteria. Patients must have stable organ function at enrollment. Eligible subjects not receiving active treatments for amyloidosis affecting their kidneys, heart, aerodigestive tracts, peripheral or autonomic nervous system(s), lungs, eyes, skin, bladder, or breasts will undergo evaluations at baseline, 6 months, and 12 months - or more frequently as clinically indicated.

Over 45 years experience indicates doxycycline is a safe, well tolerated antibiotic. The investigators will use standard grading systems to assess doxycycline response following twelve months of treatment.

Read the detailed description

In transgenic animal models of disease, the tetracycline antibiotic doxycycline disrupts A beta amyloid fibrils (AB) in Alzheimer's disease, transthyretin (ATTR) amyloid fibrils in familial amyloidotic polyneuropathy, and immunoglobulin light chain (AL) amyloid fibrils.

The aim of this single-center, 12-month open label, prospective phase II study was to determine a) the safety and tolerability of prolonged full dose doxycycline in patients with amyloidosis, and b) the effect of doxycycline treatment on amyloid-induced organ dysfunction.

We enrolled 25 patients with measurable organ dysfunction caused by amyloid deposition who were not receiving active treatment to control their amyloid production. All 25 subjects received doxycycline 100 mg by both twice daily for up to 12 months depending on their tolerance of the antibiotic. The primary endpoint, defined by the organ most affected by amyloid, was measured at baseline, 6 and 12 months along with safety laboratory values.

Conditions: Amyloidosis
Being tested: Doxycycline 100 mg po bid x 12 months
Keywords: AL Amyloidosis, Primary Amyloidosis, Hereditary Amyloidosis, Familial Amyloidosis, SSA Amyloidosis, Senile Systemic Amyloidosis, AA Amyloidosis, Secondary Amyloidosis, Localized Amyloidosis, Systemic Amyloidosis
Medical subject headings: Amyloidosis, Immunoglobulin Light-chain Amyloidosis, Amyloidosis, Familial, AA amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Doxycycline 100 mg po bid x 12 monthsDrug
Also called CAS: 564-25-0; ATC code: J01AA02 A01AB22; PubChem: CID 11256
100mg by mouth twice daily for 1 year.

Study groups in NCT01677286
Study group	Role	What they receive
doxycycline 100 mg po bid x 12 months	Experimental	Open-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months. Receives: Drug: Doxycycline 100 mg po bid x 12 months

What is being measured

The primary outcome is the main question the study is designed to answer.

Amyloid Cardiomyopathy: BNP
Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at end of study reported
Measured: 12 months
Amyloid Cardiomyopathy: Troponin I
Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at change at end of study reported
Measured: 12 months
Amyloid Nephropathy: Creatinine Clearance
Creatinine clearance (ml/min) and proteinuria (g/day) were assessed at baseline, 6 and 12 months, with change at change at end of study reported
Measured: 12 months
Amyloid Nephropathy: Proteinuria
Patients with predominant amyloid kidney involvement at enrollment.
Measured: Data were assessed at baseline, 6 and 12 months, with change at end of study reported

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 201215 Dec 2015

First posted3 Sep 2012 (estimated)
Study startJul 2012
Primary completion22 May 2015
Study completion15 Dec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for AmyloidosisStudies of the same condition, open and under way.
More trials run by Boston 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: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01677286
Sponsor's protocol ID: H-31546
Status last verified: Jul 2017
First submitted: 21 Aug 2012
Last updated: 1 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided: Primary manuscript reporting outcomes is in preparation. Once completed, we will consider IPD sharing plan.

Publications

Cardoso I, Merlini G, Saraiva MJ. 4'-iodo-4'-deoxydoxorubicin and tetracyclines disrupt transthyretin amyloid fibrils in vitro producing noncytotoxic species: screening for TTR fibril disrupters. FASEB J. 2003 May;17(8):803-9. doi: 10.1096/fj.02-0764com.
PubMed 12724338
Cardoso I, Saraiva MJ. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J. 2006 Feb;20(2):234-9. doi: 10.1096/fj.05-4509com.
PubMed 16449795
Forloni G, Colombo L, Girola L, Tagliavini F, Salmona M. Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett. 2001 Jan 5;487(3):404-7. doi: 10.1016/s0014-5793(00)02380-2.
PubMed 11163366
Ward JE, Ren R, Toraldo G, Soohoo P, Guan J, O'Hara C, Jasuja R, Trinkaus-Randall V, Liao R, Connors LH, Seldin DC. Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis. Blood. 2011 Dec 15;118(25):6610-7. doi: 10.1182/blood-2011-04-351643. Epub 2011 Oct 12.
PubMed 21998211
Obici L, Cortese A, Lozza A, Lucchetti J, Gobbi M, Palladini G, Perlini S, Saraiva MJ, Merlini G. Doxycycline plus tauroursodeoxycholic acid for transthyretin amyloidosis: a phase II study. Amyloid. 2012 Jun;19 Suppl 1:34-6. doi: 10.3109/13506129.2012.678508. Epub 2012 May 2.
PubMed 22551192
Giorgetti S, Raimondi S, Pagano K, Relini A, Bucciantini M, Corazza A, Fogolari F, Codutti L, Salmona M, Mangione P, Colombo L, De Luigi A, Porcari R, Gliozzi A, Stefani M, Esposito G, Bellotti V, Stoppini M. Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils. J Biol Chem. 2011 Jan 21;286(3):2121-31. doi: 10.1074/jbc.M110.178376. Epub 2010 Nov 10.
PubMed 21068391
Cardoso I, Martins D, Ribeiro T, Merlini G, Saraiva MJ. Synergy of combined doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models. J Transl Med. 2010 Jul 30;8:74. doi: 10.1186/1479-5876-8-74.
PubMed 20673327

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Essen Amyloidosis Registry
Amyloidosis; Systemic, Amyloidosis Cardiac
RecruitingPhase 1
Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis
Relapsed/Refractory AL Amyloidosis
Active, not recruitingPhase 2
Siltuximab to Decrease Symptom Burden After Autologous Stem Cell Transplantation for Patients With Multiple Myeloma and AL Amyloidosis
Multiple Myeloma, AL Amyloidosis
Active, not recruitingPhase 3
A Phase 3 Study of NTLA-2001 in ATTRv-PN
Neuromuscular Disease, Neuromuscular Diseases (NMD)
RecruitingPhase 3
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

All Amyloidosis trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study of Doxycycline in Patients With Amyloidosis
ClinicalTrials.gov ID: NCT01677286
Acronym / sponsor ID: H-31546
Conditions: Amyloidosis
Keywords: AL Amyloidosis, Primary Amyloidosis, Hereditary Amyloidosis, Familial Amyloidosis, SSA Amyloidosis, Senile Systemic Amyloidosis, AA Amyloidosis, Secondary Amyloidosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: Boston UniversityUniversity, hospital or other
Study start: Jul 2012 (actual)
Primary completion: 22 May 2015 (actual)
Study completion: 15 Dec 2015 (actual)
First posted: 3 Sep 2012 (estimated)
Results: Posted 6 Jun 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
doxycycline 100 mg po bid x 12 months	Experimental	Drug: Doxycycline 100 mg po bid x 12 monthsOpen-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Age 18 or older
Biopsy-proven amyloidosis
Biochemical or clinical evidence of amyloid induced end-organ dysfunction

Key exclusion criteria (9 listed)

Concurrent use of other tetracyclines
Ongoing active treatment for amyloidosis
Pregnancy or unwillingness to use contraception by women of childbearing age
Doxycycline drug allergy/hypersensitivity
ECOG performance status > 3

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
Doxycycline 100 mg po bid x 12 monthsAlso: CAS: 564-25-0; ATC code: J01AA02 A01AB22; PubChem: CID 11256100mg by mouth twice daily for 1 year.	Drug	doxycycline 100 mg po bid x 12 months

Primary outcome

Amyloid Cardiomyopathy: BNP
Time frame: 12 months
Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at end of study reported
Amyloid Cardiomyopathy: Troponin I
Time frame: 12 months
Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at change at end of study reported
Amyloid Nephropathy: Creatinine Clearance
Time frame: 12 months
Creatinine clearance (ml/min) and proteinuria (g/day) were assessed at baseline, 6 and 12 months, with change at change at end of study reported
Amyloid Nephropathy: Proteinuria
Time frame: Data were assessed at baseline, 6 and 12 months, with change at end of study reported
Patients with predominant amyloid kidney involvement at enrollment.

Results and safety

Results posted to the registry on 6 Jun 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Doxycycline 100 mg po Bid x 12 Months	25	14

Primary outcome: Amyloid Cardiomyopathy: BNP

Time frame: 12 months. Mean (Standard Deviation). Unit: pg/mL

Measure	Cardiomyopathy n = 12
Value	883 (703)

Cardiomyopathy: Mean outcome change: 171 (95% CI 14.1 to 328), p = 0.035, Mixed Models Analysis

Population analysed: Analysis is limited to the patients with predominant amyloid heart involvement at enrollment. Mixed models analyses of change from baseline levels of cardiac biomarkers (BNP, Troponin I) were performed to include all collected data.

Primary outcome: Amyloid Cardiomyopathy: Troponin I

Time frame: 12 months. Mean (Standard Deviation). Unit: ng/mL

Measure	Cardiomyopathy n = 12
Value	0.15 (0.07)

Cardiomyopathy: Mean outcome change: 0.0072 (95% CI -0.009 to 0.0234), p = 0.340, Mixed Models Analysis

Population analysed: Patients with predominant amyloid involvement of the heart.

Primary outcome: Amyloid Nephropathy: Creatinine Clearance

Time frame: 12 months. Mean (Standard Deviation). Unit: ml/min

Measure	Amyloid Nephropathy n = 10
Value	82.4 (48.0)

Amyloid Nephropathy: Change in outcome measure: -7.39 (95% CI -13.12 to -1.67), p = 0.017, Mixed Models Analysis

Population analysed: Analysis is limited to the patients with predominant amyloid kidney involvement at enrollment. Mixed models analyses of change from baseline levels of creatinine clearance (ml/min) and proteinuria (g/day) were performed to include all collected data.

Primary outcome: Amyloid Nephropathy: Proteinuria

Time frame: Data were assessed at baseline, 6 and 12 months, with change at end of study reported. Mean (Standard Deviation). Unit: g/day

Measure	Amyloid Nephropathy: Proteinuria (g/Day) n = 10
Value	5.91 (3.85)

Amyloid Nephropathy: Proteinuria (g/Day): Change in outcome measure: 0.091 (95% CI -0.285 to 0.466), p = 0.603, Mixed Models Analysis

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Doxycycline 100 mg po Bid x 12 Months	12 of 25 (48%)	21 of 25 (84%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12724338Cardoso I, Merlini G, Saraiva MJ. 4'-iodo-4'-deoxydoxorubicin and tetracyclines disrupt transthyretin amyloid fibrils in vitro producing noncytotoxic species: screening for TTR fibril disrupters. FASEB J. 2003 May;17(8):803-9. doi: 10.1096/fj.02-0764com.
Background: PubMed 16449795Cardoso I, Saraiva MJ. Doxycycline disrupts transthyretin amyloid: evidence from studies in a FAP transgenic mice model. FASEB J. 2006 Feb;20(2):234-9. doi: 10.1096/fj.05-4509com.
Background: PubMed 11163366Forloni G, Colombo L, Girola L, Tagliavini F, Salmona M. Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett. 2001 Jan 5;487(3):404-7. doi: 10.1016/s0014-5793(00)02380-2.
Background: PubMed 21998211Ward JE, Ren R, Toraldo G, Soohoo P, Guan J, O'Hara C, Jasuja R, Trinkaus-Randall V, Liao R, Connors LH, Seldin DC. Doxycycline reduces fibril formation in a transgenic mouse model of AL amyloidosis. Blood. 2011 Dec 15;118(25):6610-7. doi: 10.1182/blood-2011-04-351643. Epub 2011 Oct 12.
Background: PubMed 22551192Obici L, Cortese A, Lozza A, Lucchetti J, Gobbi M, Palladini G, Perlini S, Saraiva MJ, Merlini G. Doxycycline plus tauroursodeoxycholic acid for transthyretin amyloidosis: a phase II study. Amyloid. 2012 Jun;19 Suppl 1:34-6. doi: 10.3109/13506129.2012.678508. Epub 2012 May 2.
Background: PubMed 21068391Giorgetti S, Raimondi S, Pagano K, Relini A, Bucciantini M, Corazza A, Fogolari F, Codutti L, Salmona M, Mangione P, Colombo L, De Luigi A, Porcari R, Gliozzi A, Stefani M, Esposito G, Bellotti V, Stoppini M. Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils. J Biol Chem. 2011 Jan 21;286(3):2121-31. doi: 10.1074/jbc.M110.178376. Epub 2010 Nov 10.
Background: PubMed 20673327Cardoso I, Martins D, Ribeiro T, Merlini G, Saraiva MJ. Synergy of combined doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models. J Transl Med. 2010 Jul 30;8:74. doi: 10.1186/1479-5876-8-74.
Individual participant dataSharing planned: Undecided. Primary manuscript reporting outcomes is in preparation. Once completed, we will consider IPD sharing plan.

Related trials for Amyloidosis

RecruitingObservational study
Essen Amyloidosis Registry
Amyloidosis; Systemic, Amyloidosis Cardiac
RecruitingPhase 1
Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis
Relapsed/Refractory AL Amyloidosis
Active, not recruitingPhase 2
Siltuximab to Decrease Symptom Burden After Autologous Stem Cell Transplantation for Patients With Multiple Myeloma and AL Amyloidosis
Multiple Myeloma, AL Amyloidosis
Active, not recruitingPhase 3
A Phase 3 Study of NTLA-2001 in ATTRv-PN
Neuromuscular Disease, Neuromuscular Diseases (NMD)
RecruitingPhase 3
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy

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.

John L Berk, M.D. principal investigator

Boston University

1 site 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 100 mg po bid x 12 months in people with Amyloidosis, run by Boston University at 1 site in United States.

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 3 inclusion and 9 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 1 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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?

Yes. Results are posted in the registry (first posted 6 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Amyloid Cardiomyopathy: BNP (time frame: 12 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01677286, which also lists 7 linked publications.

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 1 Aug 2017.