Clinical Trial: Safety and Effect of Doxycycline in Patients With Amyloidosis

Study Status: Not yet recruiting
Recruit Status: Unknown status
Study Type: Interventional

Official Title: 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 Summary:
Sponsor: Boston University

Current Primary Outcome: Composite measures specific to the organ system affected by amyloidosis at study entry [ Time Frame: 12 months ]

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:

  1. airway -- PFTs, CT imaging, endoscopic visualization
  2. gastrointestinal -- endoscopic visualization
  3. bladder -- CT imaging, cystoscopy, urodynamics
  4. skin -- direct measures of disease


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Quality of Life [ Time Frame: 12 months ]
    Quality of Life (SF-36)
  • Kumamoto neurologic score [ Time Frame: 12 months ]
    Motor, sensory, autonomic measures of neuropathy


Original Secondary Outcome: Same as current

Information By: Boston University

Dates:
Date Received: August 21, 2012
Date Started: July 2012
Date Completion: December 2015
Last Updated: January 2, 2015
Last Verified: January 2015