Safety and Effect of Doxycycline in Patients With Amyloidosis

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

John L. Berk, Boston University

ClinicalTrials.gov Identifier:

NCT01677286

First received: August 21, 2012

Last updated: January 2, 2015

Last verified: January 2015

History of Changes

Tracking Information

First Received Date ^ICMJE

August 21, 2012

Last Updated Date

January 2, 2015

Start Date ^ICMJE

July 2012

Estimated Primary Completion Date

June 2015 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Composite measures specific to the organ system affected by amyloidosis at study entry [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Amyloid nephropathy: 24 hour urine protein excretion, creatinine clearance

Amyloid cardiomyopathy: cardiac biomarkers (BNP, Troponin I), echo parameters (IVSd, longitudinal strain, diastolic indices [e/e']), ECG

Amyloid peripheral neuropathy: Neurologic Impairment Score-Lower Limb (NIS-LL), modified body mass index (mBMI)

Amyloid autonomic neuropathy: postural blood pressures, heart rate variability, mBMI

Localized amyloidosis:

airway -- PFTs, CT imaging, endoscopic visualization
gastrointestinal -- endoscopic visualization
bladder -- CT imaging, cystoscopy, urodynamics
skin -- direct measures of disease

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT01677286 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Quality of Life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Quality of Life (SF-36)
Kumamoto neurologic score [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Motor, sensory, autonomic measures of neuropathy

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

Safety and Effect of Doxycycline in Patients With Amyloidosis

Official Title ^ICMJE

A Phase II Study of Doxycycline in Patients With Amyloidosis

Brief 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. 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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 2

Study Design ^ICMJE

Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Amyloidosis

Intervention ^ICMJE

Drug: Doxycycline 100 mg po bid x 12 months

100mg by mouth twice daily for 1 year.

Other Name: CAS: 564-25-0; ATC code: J01AA02 A01AB22; PubChem: CID 11256

Study Arm (s)

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.

Intervention: Drug: Doxycycline 100 mg po bid x 12 months

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.
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.
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.
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. Journal of Translational Medicine. 2010;8:74.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Active, not recruiting

Estimated Enrollment ^ICMJE

Estimated Completion Date

December 2015

Estimated Primary Completion Date

June 2015 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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%

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT01677286

Other Study ID Numbers ^ICMJE

H-31546

Has Data Monitoring Committee

Responsible Party

John L. Berk, Boston University

Study Sponsor ^ICMJE

Boston University

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Principal Investigator:

John L Berk, M.D.

Boston University

Information Provided By

Boston University

Verification Date

January 2015

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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