Text Size

Safety and Effect of Doxycycline in Patients With Amyloidosis

This study is currently recruiting participants.
Verified May 2013 by Boston University
Sponsor:
Information provided by (Responsible Party):
John L. Berk, Boston University
ClinicalTrials.gov Identifier:
NCT01677286
First received: August 21, 2012
Last updated: May 12, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Amyloidosis
 Drug: Doxycycline
 Phase 2

Study Type: Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Amyloidosis
U.S. FDA Resources

Further study details as provided by Boston University:

Primary Outcome Measures:
  • 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

    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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 60
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxycycline Drug: Doxycycline
100mg by mouth twice daily for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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%
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01677286

Contacts
Contact: Samantha Pappin 617-638-4494 Samantha.Pappin@bmc.org

Locations
United States, Massachusetts
Boston University Recruiting
Boston, Massachusetts, United States, 02118
Principal Investigator: John L Berk, M.D.            
Sponsors and Collaborators
Boston University
Investigators
Principal Investigator: John L Berk, M.D. Boston University
  More Information

Publications:

Responsible Party: John L. Berk, Clinical Director, Amyloid Treatment & Research Program, Boston University
ClinicalTrials.gov Identifier: NCT01677286     History of Changes
Other Study ID Numbers: H-31546
Study First Received: August 21, 2012
Last Updated: May 12, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Boston University:
AL Amyloidosis
Primary Amyloidosis
Hereditary Amyloidosis
Familial Amyloidosis
SSA Amyloidosis
 Senile Systemic Amyloidosis
AA Amyloidosis
Secondary Amyloidosis
Localized Amyloidosis
Systemic Amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Doxycycline
Doxycycline hyclate
Anti-Bacterial Agents
 Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on May 16, 2013