This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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
August 21, 2012
July 4, 2017
July 2012
May 22, 2015   (Final data collection date for primary outcome measure)
  • 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.
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
Complete list of historical versions of study NCT01677286 on ClinicalTrials.gov Archive Site
Not Provided
  • 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
Not Provided
Not Provided
 
Safety and Effect of Doxycycline in Patients With Amyloidosis
A Phase II Study 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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Amyloidosis
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
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.
Intervention: Drug: Doxycycline 100 mg po bid x 12 months

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
25
December 15, 2015
May 22, 2015   (Final data collection date for primary outcome measure)

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%
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01677286
H-31546
No
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
Plan to Share IPD: Undecided
Plan Description: Primary manuscript reporting outcomes is in preparation. Once completed, we will consider IPD sharing plan.
John L. Berk, Boston University
Boston University
Not Provided
Principal Investigator: John L Berk, M.D. Boston University
Boston University
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP