Safety and Effect of Doxycycline in Patients With Amyloidosis

• Status: Completed
• Trial end date: 2015-12-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Boston University
• Treatments: Doxycycline

Criteria

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%