Safety and Effect of Doxycycline in Patients With Amyloidosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
John L. Berk, Boston University
ClinicalTrials.gov Identifier:
NCT01677286
First received: August 21, 2012
Last updated: January 2, 2015
Last verified: January 2015
  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 100 mg po bid x 12 months
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:


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: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01677286

Locations
United States, Massachusetts
Boston University
Boston, Massachusetts, United States, 02118
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: January 2, 2015
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:
Doxycycline
Amyloidosis
Metabolic Diseases
Proteostasis Deficiencies
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2015