Safety and Effect of Doxycycline in Patients With Amyloidosis

Boston University

Status and phase: Completed; Phase 2

Conditions: Amyloidosis

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

Study type: Interventional

Funder types: Other

Identifiers

NCT01677286

H-31546

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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%

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

doxycycline 100 mg po bid x 12 months

Experimental group

Description:

Open-label doxycycline 100 mg twice daily by mouth will be administered to subjects for 12 months.

Treatment:

Drug: Doxycycline 100 mg po bid x 12 months