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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 June 2016 by University of Maryland
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Michael Terrin, University of Maryland
ClinicalTrials.gov Identifier:
NCT01756833
First received: December 20, 2012
Last updated: June 17, 2016
Last verified: June 2016
  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: Two and one-half to three 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: Two and one-half to three 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: Two and one-half to three 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: Two and one-half to three years ] [ Designated as safety issue: No ]
  • Aneurysm rupture [ Time Frame: Two and one-half to three years ] [ Designated as safety issue: No ]
  • Surgical intervention [ Time Frame: Two and one-half to three years ] [ Designated as safety issue: No ]
  • Death [ Time Frame: Two and one-half to three years ] [ Designated as safety issue: No ]

Estimated Enrollment: 258
Study Start Date: May 2013
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2018 (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
100 mg po bid
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
capsule identical to the doxycycline capsule
Other Name: capsule containing inert filler

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. Nineteen clinical sites have identified pools of over 1600 patients with small aneurysm who meet the proposed inclusion/exclusion criteria. Two hundred fifty-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   (Adult, Senior)
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

  Show 24 Study Locations
Sponsors and Collaborators
University of Maryland
National Institute on Aging (NIA)
Investigators
Principal Investigator: Michael L Terrin, MD University of Maryland
Principal Investigator: Bernard T Baxter, MD University of Nebraska
Principal Investigator: Jonathan Matsumura, MD University of Wisconsin Medical Center
Principal Investigator: John Curci, MD Vanderbilt University
  More Information

Responsible Party: Michael Terrin, 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: June 17, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes

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
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on September 23, 2016