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Safety and Effect of Doxycycline in Patients With Amyloidosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John L. Berk, Boston University
ClinicalTrials.gov Identifier:
NCT01677286
First received: August 21, 2012
Last updated: July 4, 2017
Last verified: July 2017
  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: Intervention Model: Single Group Assignment
Masking: None (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 John L. Berk, Boston University:

Primary Outcome Measures:
  • Amyloid Cardiomyopathy: BNP [ Time Frame: 12 months ]
    Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at end of study reported

  • Amyloid Cardiomyopathy: Troponin I [ Time Frame: 12 months ]
    Cardiac biomarkers (BNP, Troponin I) were assessed at baseline, 6 and 12 months, with change at change at end of study reported

  • Amyloid Nephropathy: Creatinine Clearance [ Time Frame: 12 months ]
    Creatinine clearance (ml/min) and proteinuria (g/day) were assessed at baseline, 6 and 12 months, with change at change at end of study reported

  • Amyloid Nephropathy: Proteinuria [ Time Frame: Data were assessed at baseline, 6 and 12 months, with change at end of study reported ]
    Patients with predominant amyloid kidney involvement at enrollment.


Enrollment: 25
Actual Study Start Date: July 2012
Study Completion Date: December 15, 2015
Primary Completion Date: May 22, 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

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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, Assistant Director, Amyloidosis Center, Boston University
ClinicalTrials.gov Identifier: NCT01677286     History of Changes
Other Study ID Numbers: H-31546
Study First Received: August 21, 2012
Results First Received: March 19, 2017
Last Updated: July 4, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Primary manuscript reporting outcomes is in preparation. Once completed, we will consider IPD sharing plan.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by John L. Berk, 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
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on August 21, 2017