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Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA^3CT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Maryland
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Michael Terrin, MD, University of Maryland
ClinicalTrials.gov Identifier:
NCT01756833
First received: December 20, 2012
Last updated: November 20, 2013
Last verified: November 2013
  Purpose

The primary aim of this study is to determine if doxycycline (100 mg bid) will inhibit (by at least 40%) the increase in greatest transverse diameter of small abdominal aortic aneurysms (3.5-5.0 cm in men, 3.5-4.5 cm in women) over a 24-month period of observation in comparison to a placebo-treated control group.


Condition Intervention Phase
Aneurysm
Drug: Doxycycline
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA^3CT)

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • The primary outcome is growth in abdominal aortic aneurysm (AAA) maximum transverse diameter determined by CT scans at two-year follow-up with allowance for baseline (pre-randomization) diameter. [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
    Based on an anticipated growth rate of 2.5 mm per year in the placebo group and the current threshold at which surgical intervention will be offered to trial participants, (5.5 cm in men, 5.0 cm in women), the upper limit of AAA size for inclusion has been set at 5.0 cm for men and 4.5 cm for women. Among these subjects, the threshold for surgical repair would be exceeded only by those exhibiting persistent growth.


Secondary Outcome Measures:
  • Secondary outcomes will determine if doxycycline affects other measures, e.g., MMP-9 levels in plasma, and whether these effects are related to aneurysm growth. [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
    Secondary outcomes will derive from central, Imaging Core Laboratory analyses of the CT scans performed every six months on patients and from the clinical follow-up of randomized patients, from clinical observation, local laboratory findings, study visit quality of life assessments, and from biomarker analyses to be performed in the Biomarkers Core Laboratory (e.g., changes from initial matrix metalloproteinase (MMP-9) levels, and matrix metalloproteinase (MMP-9) levels at 24 months of follow-up).

  • Secondary outcomes will determine if doxycycline affects other measures, e.g., Interferon-gamma levels, and whether these effects are related to aneurysm growth. [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
    Secondary outcomes will derive from central, Imaging Core Laboratory analyses of the CT scans performed every six months on patients and from the clinical follow-up of randomized patients, from clinical observation, local laboratory findings, study visit quality of life assessments, and from biomarker analyses to be performed in the Biomarkers Core Laboratory (e.g., changes from initial Interferon-gamma levels, and Interferon-gamma levels at 24 months of follow-up).


Other Outcome Measures:
  • Aneurysm volume and other characteristics [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Aneurysm rupture [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Surgical intervention [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Death [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]

Estimated Enrollment: 248
Study Start Date: May 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Doxycycline
100 mg capsules, twice a day, for a period of two years.
Drug: Doxycycline
Other Names:
  • doxycycline hyclate
  • Vibramycin
  • Oracea
  • Adoxa
  • Atridox and others
Placebo Comparator: Placebo
100 mg capsules, twice a day, for a period of two years.
Drug: Placebo

Detailed Description:

N-TA^3CT is a randomized, double-blind, placebo-controlled test of the hypothesis that doxycycline 100 mg bid, will reduce the rate of increase of maximum transverse diameter of small (3.5-5.0 cm among men and 3.5 to 4.5 cm among women) abdominal aortic aneurysms. The primary outcome is abdominal aortic aneurysm (AAA) maximum transverse diameter determined by CT scans at two-year follow-up with allowance for baseline (pre-randomization) diameter. Based on an anticipated growth rate of 2.5 mm per year in the placebo group and the current threshold at which surgical intervention will be offered to trial participants, (5.5 cm in men, 5.0 cm in women), the upper limit of AAA size for inclusion has been set at 5.0 cm for men and 4.5 cm for women. Among these subjects, the threshold for repair would be exceeded only by those exhibiting persistent growth. Secondary outcomes will determine if doxycycline affects other measures, e.g., MMP-9 levels in plasma and whether these effects are related to aneurysm growth. Fifteen clinical sites have identified pools of over 900 patients with small aneurysm who meet the proposed inclusion/exclusion criteria. Two hundred forty-eight patients will be randomized to placebo or doxycycline and their aneurysms followed for change in diameter at six-month intervals using CT imaging. The alternative hypothesis is that doxycycline will inhibit the expansion rate by 40% during the two years of observation. Patients enrolling in N-TA^3CT must be able to give consent for their participation themselves and meet study eligibility criteria.

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients 55 years of age or older, women post-surgical menopause or at least two years since last menses if natural menopause.
  • CT scan documented infrarenal abdominal aortic aneurysm with maximum transverse diameter larger than 35 mm and no greater than 50 mm, in men, and larger than 35 mm and no greater than 45 mm in women.

Exclusion Criteria:

  • Patients will be excluded from the study if they are unable to give their own informed consent to participate.
  • have symptoms related to abdominal aortic aneurysm.
  • have other intra-abdominal vascular pathology that may require repair within 24 months (e.g., renal artery stenosis, large iliac artery aneurysms, iliac occlusive disease, aneurysmal involvement of the renal artery).
  • have had previous abdominal aortic aneurysm repair by open surgical or endovascular technique.
  • have an active malignancy with life expectancy less than two years.
  • have an allergy to tetracycline.
  • are currently or have been recently treated (previous six months) with tetracycline derivatives.
  • they are currently taking anti-seizure medicines metabolized by pathways influenced by doxycycline (e.g., carbamazepine, phenytoin, and barbiturates).
  • stage II hypertension (patients whose blood pressure is persistently in the range of systolic > 160 mm Hg or diastolic > 100 mm Hg despite primary physician's best effort to achieve adequate therapy.
  • have dialysis dependent renal failure or impending dialysis treatment for renal insufficiency.
  • have a chronic infection requiring long-term (> 2 weeks) antibiotics.
  • have known genetic syndromes responsible for the abdominal aortic aneurysm (e.g., Marfan's Syndrome).
  • are under treatment with systemic immunosuppressive agents.
  • could become pregnant.
  • are not good candidates for clinical trial participation.
  • are enrolled in another clinical trial.
  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: NCT01756833

Contacts
Contact: Michael L Terrin, MD 410-706-6139 mterrin@epi.umaryland.edu
Contact: Andrea Lefever 410-706-4411 alefever@epi.umaryland.edu

Locations
United States, Arizona
University of Arizona Medical Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Joseph Mills, MD    520-626-6670    jmills@surgery.arizona.edu   
Contact: Heather Leigh, RN    520-626-4845    hleigh@surgery.arizona.edu   
Principal Investigator: Joseph Mills, MD         
United States, Florida
Baptist Health Medical Center Recruiting
Miami, Florida, United States, 33176
Contact: Barry Katzen, MD    786-596-5990    BARRYK@baptisthealth.net   
Contact: Susan Arp    786-596-5972    susanar@baptisthealth.net   
Principal Investigator: Barry Katzen, MD         
University of South Florida Health Center Recruiting
Tampa, Florida, United States, 33606
Contact: Murray Shames, MD    813-259-0921    mshames@health.usf.edu   
Contact: Stephenie Yapchanyk, RN    813-259-0683    syapchan@health.usf.edu   
Principal Investigator: Murray Shames, MD         
United States, Illinois
Northwestern University Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: William Pearce, MD    312-695-2716    wpearce@nmh.edu   
Contact: Michelle Endo    312-695-2928    mendo@nmh.edu   
Principal Investigator: William Pearce, MD         
United States, Maryland
University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Robert Crawford, MD    410-328-5840    rcrawford@smail.umaryland.edu   
Contact: Debbie Nesbitt, RN    410-605-7435    debbie.nesbitt@va.gov   
Principal Investigator: Robert Crawford, MD         
United States, Massachusetts
Beth Israel Deaconness Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Mark Wyers, MD    617-632-9956    mwyers@bidmc.harvard.edu   
Contact: Mary Trovato, RN    617-632-7488    mtrovato@bidmc.harvard.edu   
Principal Investigator: Mark Wyers, MD         
United States, Michigan
University of Michigan Medical Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Jonathan Eliason, MD    734-936-5786    jonaelia@med.umich.edu   
Contact: Susan Blackburn    734-936-8556    susablac@med.umich.edu   
Principal Investigator: Jonathan Eliason, MD         
Sub-Investigator: John Rectenwald, MD         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Robert Thompson, MD    314-362-7410    thompson@wudosis.wustl.edu   
Contact: Jennifer Wille, RN    314-362-6217    willej@wudosis.wustl.edu   
Principal Investigator: Robert Thompson, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Jason MacTaggart, MD    402-559-4395    jmactaggart@unmc.edu   
Contact: Karen Taylor, RN    402-559-3935    kttaylor@unmc.edu   
Principal Investigator: Jason MacTaggart, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: James McKinsey, MD    212-342-3255    jfm2111@columbia.edu   
Contact: Diana Catz, PhD    212-342-4102    dsc6@columbia.edu   
Principal Investigator: James McKinsey, MD         
United States, Ohio
University of Cincinnati Medical Center Withdrawn
Cincinnati, Ohio, United States, 45267
Cleveland Clinic, Lerner College of Medicine Withdrawn
Cleveland, Ohio, United States, 44195
United States, Oregon
Oregon Health Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Gregory Moneta, MD    503-494-7593    monetag@ohsu.edu   
Contact: Sharon Kryger, BS    503-494-7477    krygers@ohsu.edu   
Principal Investigator: Gregory Moneta, MD         
United States, Pennsylvania
Geisinger Medical Center Recruiting
Danville, Pennsylvania, United States, 17822
Contact: James Elmore, MD    570-271-6369    jelmore@geisinger.edu   
Contact: Elisabeth Deetz, RN    570-214-9321    emdeetz@geisinger.edu   
Principal Investigator: James Elmore, MD         
United States, Utah
University of Utah Health Sciences Center Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Larry Kraiss, MD    801-581-8301    larry.kraiss@hsc.utah.edu   
Contact: Maria Maloney    801-585-3663    maria.maloney@hsc.utah.edu   
Principal Investigator: Larry Kraiss, MD         
United States, Virginia
University of Virginia Medical Center Withdrawn
Charlottesville, Virginia, United States, 22908
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Michael L Terrin, MD University of Maryland, Baltimore County
Principal Investigator: Bernard T Baxter, MD University of Nebraska
Principal Investigator: Jonathan Matsumura, MD University of Wisconsin Medical Center
Principal Investigator: John Curci, MD Washington University School of Medicine
  More Information

No publications provided

Responsible Party: Michael Terrin, MD, Professor, University of Maryland
ClinicalTrials.gov Identifier: NCT01756833     History of Changes
Other Study ID Numbers: HP-00051170, R01AG037120
Study First Received: December 20, 2012
Last Updated: November 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
abdominal
aortic
aneurysm

Additional relevant MeSH terms:
Aneurysm
Aortic Aneurysm
Aortic Aneurysm, Abdominal
Aortic Diseases
Cardiovascular Diseases
Vascular Diseases
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014