- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01677286
Safety and Effect of Doxycycline in Patients With Amyloidosis
A Phase II Study of Doxycycline in Patients With Amyloidosis
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. If untreated, amyloid deposits impair organ function, affecting the morbidity and mortality of patients.
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02118
- Boston University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18 or older
- Biopsy-proven amyloidosis
- Biochemical or clinical evidence of amyloid induced end-organ dysfunction
Exclusion Criteria:
- 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
- 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%
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: doxycycline 100 mg po bid x 12 months
Open-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months.
|
100mg by mouth twice daily for 1 year.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
12 months
|
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
|
12 months
|
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
|
12 months
|
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.
|
Data were assessed at baseline, 6 and 12 months, with change at end of study reported
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John L Berk, M.D., Boston University
Publications and helpful links
General 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- H-31546
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Amyloidosis
-
Millennium Pharmaceuticals, Inc.CompletedLight-Chain AmyloidosisUnited States, Canada, France, Germany, Italy
-
Boston UniversityCorino Therapeutics, Inc.CompletedTransthyretin Amyloidosis | Amyloidosis, Leptomeningeal, Transthyretin-RelatedUnited States
-
Chulalongkorn UniversityUnknown
-
Criterium, Inc.AmgenCompletedAmyloidosis | Systemic Light Chain AmyloidosisUnited States
-
Steen Hvitfeldt PoulsenRecruitingTransthyretin Amyloidosis | Transthyretin Cardiac Amyloidosis | Wild-Type Transthyretin-Related (ATTR)AmyloidosisDenmark
-
IRCCS Policlinico S. MatteoRecruiting
-
University Hospital Center of MartiniqueTerminated
-
Peking Union Medical College HospitalXian-Janssen Pharmaceutical Ltd.Active, not recruitingAmyloidosis; SystemicChina
-
Kaneka Medical America LLCRecruitingDialysis AmyloidosisUnited States
-
Peking Union Medical College HospitalRecruitingLight Chain (AL) Amyloidosis | Venetoclax | CCND1 TranslocationChina
Clinical Trials on Doxycycline 100 mg po bid x 12 months
-
Lady Davis InstituteRecruitingAcneiform Eruptions | Cancer, Treatment-RelatedCanada
-
British Columbia Centre for Disease ControlUnknown
-
Lundquist Institute for Biomedical Innovation at...Unknown
-
University Medical Centre LjubljanaMedical University of Vienna; Harvard University; University of Ljubljana School...UnknownChronic Atrophic AcrodermatitisSlovenia
-
Haiphong University of Medicine and PharmacyCompletedChlamydia Trachomatis Infection | Neisseria Gonorrhoeae InfectionVietnam
-
University Medical Centre LjubljanaUniversity of Ljubljana School of Medicine, SloveniaCompleted
-
University Medical Centre LjubljanaRecruiting
-
Bristol-Myers SquibbCompleted
-
Leonardo ClavijoAmgenUnknownCritical Limb IschemiaUnited States
-
University of IowaCompletedUncomplicated Bacterial CystitisUnited States