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Completed

NCT Number: NCT01677286

Safety and Effect 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.

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Key information

Conditions

Amyloidosis AA amyloidosis Amyloidosis, Familial Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Immune System Diseases Immunoglobulin Light-chain Amyloidosis Immunoproliferative Disorders Lymphoproliferative Disorders Metabolic Diseases Metabolism, Inborn Errors Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Nutritional and Metabolic Diseases Paraproteinemias Proteostasis Deficiencies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Boston University

Boston, Massachusetts, 02118, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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%

Treatment and study plan

Doxycycline 100 mg po bid x 12 months

Drug

100mg by mouth twice daily for 1 year.

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

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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.

Sponsors and collaborators

Lead sponsor

Boston University

Other

Registry information

Official study title

A Phase II Study of Doxycycline in Patients With Amyloidosis

Important dates

Study start
2012
Primary completion
2015
Study completion
2015
First posted
Sep 3, 2012
Registry last updated
Aug 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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