Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial - Full Text View

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:

MedlinePlus related topics: Aneurysms Aortic Aneurysm

Drug Information available for: Doxycycline Doxycycline monohydrate Doxycycline Hyclate Doxycycline calcium

U.S. FDA Resources

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

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	Not yet 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	Not yet 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	Not yet 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	Not yet 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	Not yet 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	Not yet 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	Not yet recruiting
Cincinnati, Ohio, United States, 45267
Contact: George Meier, MD 513-558-3700 george.meier@uc.edu
Contact: Cindy Werner, RN 513-558-1331 cindy.werner@uc.edu
Principal Investigator: George Meier, MD
Cleveland Clinic, Lerner College of Medicine	Not yet recruiting
Cleveland, Ohio, United States, 44195
Contact: Matthew Eagleton, MD 216-445-1167 eagletm@ccf.org
Contact: Larissa Schaaf, RN 216-445-5937 schaafl@ccf.org
Principal Investigator: Matthew Eagleton, MD
United States, Oregon
Oregon Health Sciences University	Not yet 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	Not yet 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	Not yet 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	Not yet recruiting
Charlottesville, Virginia, United States, 22908
Contact: Gilbert Upchurch, MD 434-243-6333 gru6n@virginia.edu
Contact: Sandra Burks, RN, BSN 434-243-0315 sgb2c@virginia.edu
Principal Investigator: Gilbert Upchurch, MD

Sponsors and Collaborators

University of Maryland

National Institute on Aging (NIA)

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 in St. Louis

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:	May 7, 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
Vascular Diseases
Cardiovascular Diseases
Aortic 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 22, 2013

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