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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Doxycycline in Patients With Amyloidosis|
- 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
- airway -- PFTs, CT imaging, endoscopic visualization
- gastrointestinal -- endoscopic visualization
- bladder -- CT imaging, cystoscopy, urodynamics
- skin -- direct measures of disease
- 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
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
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.
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01677286
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02118|
|Principal Investigator:||John L Berk, M.D.||Boston University|